DatabaseID StudyType PubMedID Author Title Journal PublishDate Chromosome Disease Technology Species CaseID Platform CNA Connection Gene Affiliation Abstract GenomeAssembly GEO dbGaP ENA IsCancer FusionGene DatabaseID StudyType PubMedID Author Title Journal PublishDate Chromosome Disease Technology Species CaseID Platform CNA Connection Gene Affiliation Abstract GenomeAssembly GEO dbGaP ENA IsCancer FusionGene CTDB0002 Research 24462510 Julio Fernandez-Banet, Nikki P. Lee, Kin Tak Chan, Huan Gao, Xiao Liu, Wing-Kin Sung,Winnie Tan, Sheung Tat Fan, Ronnie T. Poon, Shiyong Li, Keith Ching, Paul A. Rejto, Mao Mao, Zhengyan Kan Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma Genomics 2014 Jan 1 Hepatocellular carcinoma Next Generation Sequencing Homo sapiens 117T Illumina HiSeq 2000 chr10:77254129-77359565:-1;chr11:65195677-65195803:-1;chr12:68486967-69618037:1;chr12:7093691-25298569:-1;chr13:24949808-24951540:1;chr16:25832301-25833569:-1;chr18:69827554-69829289:-1;chr18:77317033-77317075:1;chr19:45434282-45435022:-1;chr1:151216266-183227564:1;chr1:151216545-226557614:1;chr1:151216692-197000991:-1;chr1:153707307-226558570:-1;chr1:153827733-212908203:1;chr1:153829027-212908199:-1;chr1:154422953-197657552:-1;chr1:156419438-183174553:1;chr1:156419724-193352718:1;chr1:156539673-183228294:1;chr1:156539677-156660305:1;chr1:156539750-166055253:-1;chr1:156539796-162087621:-1;chr1:156540190-196263378:1;chr1:156540308-183191885:-1;chr1:156546546-226257332:1;chr1:156659962-197702859:1;chr1:156660385-159852249:1;chr1:156660627-193373804:1;chr1:157104393-159971005:-1;chr1:157105087-196464550:1;chr1:159851334-161972637:1;chr1:161349421-244937596:1;chr1:161998837-162225053:-1;chr1:162087993-226609105:-1;chr1:162361758-207117521:1;chr1:166138797-193352167:-1;chr1:168684997-183320210:-1;chr1:174008782-207113572:1;chr1:174036961-213142231:-1;chr1:179158752-203172242:-1;chr1:179252913-201536915:-1;chr1:183174569-226558257:-1;chr1:183181774-204188039:1;chr1:183188743-197001349:1;chr1:183191112-202900543:1;chr1:183217871-226558409:-1;chr1:183222686-212517877:1;chr1:183222884-197702104:-1;chr1:183226816-193373821:1;chr1:183227084-197658068:1;chr1:183227173-197658591:1;chr1:183228110-197658472:-1;chr1:183229493-193348141:-1;chr1:183320100-197702226:-1;chr1:190542073-205723232:-1;chr1:193240589-197002565:1;chr1:193329541-203172404:1;chr1:193329654-196876022:-1;chr1:193352659-212908317:1;chr1:193352728-197657694:-1;chr1:193372405-196263839:1;chr1:193373290-248071857:1;chr1:193373636-226558697:-1;chr1:193382469-226558514:1;chr1:193383174-208121707:-1;chr1:196263326-197658056:1;chr1:196263595-197658404:-1;chr1:196263694-197001376:1;chr1:196608183-202900385:1;chr1:197001051-203912534:-1;chr1:197001199-197659148:1;chr1:197001378-226558324:-1;chr1:197001415-226558398:-1;chr1:197657765-226558358:1;chr1:197657765-226558369:1;chr1:197657875-197658960:-1;chr1:197658517-213262561:1;chr1:197659157-226558564:-1;chr1:197668357-208168692:1;chr1:202900485-213262283:-1;chr1:203008523-209973625:-1;chr1:205298940-242014388:1;chr1:206887324-224549492:1;chr1:211809174-242013705:-1;chr1:221673283-221833746:-1;chr20:51623677-51623894:-1;chr2:38225978-38229325:-1;chr2:79763416-79985150:-1;chr4:39868393-40938932:1;chr4:85233794-85234156:-1;chr6:94769059-94769762:-1;chr7:86853240-144987383:-1 hs1:31893066-31893066,hs13:24788007-24788007;hs1:31893220-31893220,hs13:24949935-24949935;hs1:86002715-86002715,hs1:161998892-161998892;hs1:144836511-144836511,hs1:167412963-167412963;hs1:145486380-145486380,hs1:155179290-155179290;hs1:153829409-153829409,hs1:197000979-197000979;hs1:153829454-153829454,hs1:156539869-156539869;hs1:155880732-155880732,hs1:234376099-234376099;hs1:156539908-156539908,hs1:197657683-197657683;hs1:156540972-156540972,hs1:193373640-193373640;hs1:156660640-156660640,hs1:203912330-203912330;hs1:156660699-156660699,hs1:153829470-153829470;hs1:159851559-159851559,hs1:183136169-183136169;hs1:161701440-161701440,hs1:197882253-197882253;hs1:162358626-162358626,hs1:221611488-221611488;hs1:162362049-162362049,hs1:212908096-212908096;hs1:174071175-174071175,hs1:168622854-168622854;hs1:178667640-178667640,hs1:182956851-182956851;hs1:179081472-179081472,hs1:150792743-150792743;hs1:179149797-179149797,hs1:213323192-213323192;hs1:183191318-183191318,hs1:193372991-193372991;hs1:183191784-183191784,hs1:196263932-196263932;hs1:183227161-183227161,hs1:213262709-213262709;hs1:183227308-183227308,hs1:156660585-156660585;hs1:183227545-183227545,hs1:212516825-212516825;hs1:183229139-183229139,hs1:183259106-183259106;hs1:183229559-183229559,hs1:226558226-226558226;hs1:193241084-193241084,hs1:197658450-197658450;hs1:193241377-193241377,hs1:197001350-197001350;hs1:193331467-193331467,hs1:211853286-211853286;hs1:193348537-193348537,hs1:213263243-213263243;hs1:193348571-193348571,hs1:197668535-197668535;hs1:193352916-193352916,hs1:156419876-156419876;hs1:193372542-193372542,hs1:226558773-226558773;hs1:196263828-196263828,hs1:226558512-226558512;hs1:196576981-196576981,hs1:149986788-149986788;hs1:196961522-196961522,hs1:200079749-200079749;hs1:196972484-196972484,hs1:193382384-193382384;hs1:197001192-197001192,hs1:193352966-193352966;hs1:197657412-197657412,hs1:183230803-183230803;hs1:197658450-197658450,hs1:197001745-197001745;hs1:197658633-197658633,hs1:226558388-226558388;hs1:197666994-197666994,hs1:202900278-202900278;hs1:197702311-197702311,hs1:183228283-183228283;hs1:202900543-202900543,hs1:226558531-226558531;hs1:203180459-203180459,hs1:211853103-211853103;hs1:205299279-205299279,hs1:207105285-207105285;hs1:206974277-206974277,hs1:183224796-183224796;hs1:211740833-211740833,hs1:215718327-215718327;hs1:211809133-211809133,hs1:156540136-156540136;hs1:212517898-212517898,hs1:197001401-197001401;hs1:212908006-212908006,hs1:156539639-156539639;hs1:212908093-212908093,hs1:197001055-197001055;hs1:212908221-212908221,hs1:156660329-156660329;hs1:213262521-213262521,hs1:162358375-162358375;hs1:213262560-213262560,hs1:193348554-193348554;hs1:213353881-213353881,hs1:159851641-159851641;hs1:220858213-220858213,hs1:168122089-168122089;hs1:221611428-221611428,hs1:212517702-212517702;hs1:226558310-226558310,hs1:161971847-161971847;hs1:226558375-226558375,hs1:212517723-212517723;hs1:226558433-226558433,hs1:203770824-203770824;hs1:226558462-226558462,hs1:153707151-153707151;hs1:226558483-226558483,hs1:183227229-183227229;hs1:229318979-229318979,hs1:165739180-165739180;hs1:235588314-235588314,hs1:193792362-193792362;hs1:237894639-237894639,hs10:135333128-135333128;hs10:53668488-53668488,hs16:20411364-20411364;hs12:32492419-32492419,hs12:28489853-28489853;hs14:25715713-25715713,hs14:25837291-25837291;hs5:62966392-62966392,hs18:51802022-51802022;hs8:32680009-32680009,hs3:132264991-132264991 ABL2;APBB2;APOC1P1;ARNT;BICD1;CASC1;CCDC19;CCDC91;CD247;CFHR4;CFHR5;CNIH4;CTNNA2;DDAH1;DENND1B;DPT;ETV3;EXO1;FAM78B;FAM82A1;GATAD2B;H3F3AP4;HS3ST4;IL19;IL6R;INTS3;IQGAP3;IRF6;KCNT2;LAMC2;LHX9;LIX1L;LPCAT3;MAPKAPK2;MTX1;NMNAT2;NOS1AP;NR5A2;NSL1;OLFML2B;PARP1;PDILT;PDS5A;PIGR;PIP5K1A;PLEKHA6;POLI;PPP2R5A;PRKG1;RIT1;RPS6KC1;RYR2;SERINC2;SLC35F3;SPATA13;TBCE;TSHZ2;VASH2;ZC3H11A Pfizer Oncology, San Diego, CA, USA Elucidating the molecular basis of hepatocellular carcinoma (HCC) is crucial to developing targeted diagnostics and therapies for this deadly disease. The landscape of somatic genomic rearrangements (GRs), which can lead to oncogenic gene fusions, remains poorly characterized in HCC. We have predicted 4314 GRs including large-scale insertions, deletions, inversions and translocations based on the whole-genome sequencing data for 88 primary HCC tumor/non-tumor tissues. We identified chromothripsis in 5 HCC genomes (5.7%) recurrently affecting chromosomal arms 1q and 8q. Albumin (ALB) was found to harbor GRs, deactivating mutations and deletions in 10% of cohort. Integrative analysis identified a pattern of paired intra-chromosomal translocations flanking focal amplifications and asymmetrical patterns of copy number variation flanking breakpoints of translocations. Furthermore, we predicted 260 gene fusions which frequently result in aberrant over-expression of the 3' genes in tumors and validated 18 gene fusions, including recurrent fusion (2/88) of ABCB11 and LRP2. GRCh37/hg19 GSE25097 ERP001196 Yes CASC1,LPCAT3;CCDC19,OLFML2B;CNIH4,MAPKAPK2;DENND1B,KCNT2;DENND1B,NMNAT2;DENND1B,PARP1;ETV3,KCNT2;FAM78B,IQGAP3;GATAD2B,NSL1;IL19,NMNAT2;IQGAP3,KCNT2;IQGAP3,NMNAT2;KCNT2,DENND1B;LAMC2,KCNT2;NMNAT2,DENND1B;NMNAT2,DPT;NSL1,GATAD2B;PARP1,DENND1B;PARP1,INTS3;PARP1,NMNAT2;PARP1,PPP2R5A;PDS5A,APBB2;PPP2R5A,NMNAT2;RPS6KC1,ABL2;RPS6KC1,CCDC19;RPS6KC1,NMNAT2;SLC35F3,RIT1;ZC3H11A,PARP1 CTDB0003 Research 24462510 Julio Fernandez-Banet, Nikki P. Lee, Kin Tak Chan, Huan Gao, Xiao Liu, Wing-Kin Sung,Winnie Tan, Sheung Tat Fan, Ronnie T. Poon, Shiyong Li, Keith Ching, Paul A. Rejto, Mao Mao, Zhengyan Kan Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma Genomics 2014 Jan 1 Hepatocellular carcinoma Next Generation Sequencing Homo sapiens 206T Illumina HiSeq 2000 chr10:101134331-101134374:-1;chr10:101143033-101145802:-1;chr11:122149898-134092564:-1;chr11:65590381-76540398:-1;chr11:68444454-124736618:-1;chr11:73128420-80752310:1;chr11:74323445-79732185:1;chr1:146576320-159118830:-1;chr1:146736676-171678710:1;chr1:149235223-220750399:-1;chr1:150459539-152261925:1;chr1:150827918-216172237:-1;chr1:151465603-159352265:-1;chr1:151614533-229423173:1;chr1:151863833-205365371:-1;chr1:152631890-242335715:1;chr1:152742746-230381514:1;chr1:159461183-204755475:1;chr1:159902366-181056554:-1;chr1:163661169-227774749:1;chr1:163693223-192049853:-1;chr1:163783040-216170571:1;chr1:164712917-182996551:1;chr1:166905347-178313768:1;chr1:169336909-209391679:1;chr1:171519238-173839298:-1;chr1:174229440-178282824:-1;chr1:174805655-174820281:-1;chr1:179374223-192310590:-1;chr1:181745502-189398493:-1;chr1:184254352-229426177:-1;chr1:185935455-227264899:-1;chr1:187068878-238083701:1;chr1:189356056-196610462:-1;chr1:192553897-215691503:1;chr1:192989501-223497448:1;chr1:193192583-194601401:1;chr1:193192583-194601409:1;chr1:193751148-194040887:-1;chr1:194549288-232942000:-1;chr1:195032033-199886834:1;chr1:196393448-203706783:1;chr1:197849228-242306806:1;chr1:200472535-220406759:1;chr1:201233402-208011691:1;chr1:204457776-215758989:1;chr1:205528016-248863405:-1;chr1:216238536-227544390:1;chr1:219793875-226007670:-1;chr1:220245564-238320629:1;chr1:222290954-243306461:1;chr1:222761439-231572578:-1;chr1:224705899-248169258:1;chr1:232315322-238325295:-1;chr1:232759584-232761882:-1;chr1:234517585-234526972:-1;chr1:234873722-235522758:1;chr1:237348463-248094735:1;chr1:241007437-242757695:1;chr1:241762174-247076107:-1;chr1:242641679-243582764:-1;chr1:243309074-245820476:1;chr4:181109427-181110424:-1;chr5:178764778-178764984:1;chr5:178764786-178764984:1;chr5:33973937-33973978:-1;chr7:79115004-79205821:1;chr8:134955565-134955612:1;chr9:116780725-116801090:-1;chrX:133328467-133487475:1 hs1:111896187-111896187,hs11:65217853-65217853;hs1:146818500-146818500,hs1:200328646-200328646;hs1:146863053-146863053,hs1:232081753-232081753;hs1:149153301-149153301,hs1:145391889-145391889;hs1:149164820-149164820,hs1:179380983-179380983;hs1:150062567-150062567,hs1:215667836-215667836;hs1:150402990-150402990,hs1:243612759-243612759;hs1:150601833-150601833,hs1:150601903-150601903;hs1:151764005-151764005,hs1:165321241-165321241;hs1:154577448-154577448,hs1:225884334-225884334;hs1:155066707-155066707,hs1:155066796-155066796;hs1:155869389-155869389,hs1:162715340-162715340;hs1:158447506-158447506,hs1:235449737-235449737;hs1:159458286-159458286,hs1:178276568-178276568;hs1:161720490-161720490,hs1:161303252-161303252;hs1:162050228-162050228,hs1:179375991-179375991;hs1:162698316-162698316,hs1:161063421-161063421;hs1:163326962-163326962,hs1:181751146-181751146;hs1:165763955-165763955,hs1:202770635-202770635;hs1:168808434-168808434,hs1:196692913-196692913;hs1:171186678-171186678,hs1:182132210-182132210;hs1:178016006-178016006,hs1:154383252-154383252;hs1:178321060-178321060,hs1:191871196-191871196;hs1:179014260-179014260,hs1:159192967-159192967;hs1:179329259-179329259,hs1:193670940-193670940;hs1:181049481-181049481,hs1:201262059-201262059;hs1:183470358-183470358,hs1:171459756-171459756;hs1:183496068-183496068,hs1:248862991-248862991;hs1:187064952-187064952,hs1:163778920-163778920;hs1:188389276-188389276,hs1:219312420-219312420;hs1:188514228-188514228,hs1:209753183-209753183;hs1:192714059-192714059,hs1:147105620-147105620;hs1:193673677-193673677,hs1:196139605-196139605;hs1:194087018-194087018,hs1:220403200-220403200;hs1:199402572-199402572,hs1:206813601-206813601;hs1:200078852-200078852,hs1:208060345-208060345;hs1:200078920-200078920,hs1:180739519-180739519;hs1:201744318-201744318,hs1:159347886-159347886;hs1:203932050-203932050,hs1:221949487-221949487;hs1:205042012-205042012,hs1:212532087-212532087;hs1:205463738-205463738,hs1:205798201-205798201;hs1:206974257-206974257,hs1:242316699-242316699;hs1:207558305-207558305,hs1:201747590-201747590;hs1:210964274-210964274,hs1:235467231-235467231;hs1:212518361-212518361,hs1:199673532-199673532;hs1:214240872-214240872,hs1:215668677-215668677;hs1:215659601-215659601,hs1:151471494-151471494;hs1:216613413-216613413,hs1:248206843-248206843;hs1:219045452-219045452,hs1:234752056-234752056;hs1:219549963-219549963,hs1:186085962-186085962;hs1:219706673-219706673,hs1:184079100-184079100;hs1:220241414-220241414,hs1:246862847-246862847;hs1:221564763-221564763,hs1:246317011-246317011;hs1:221610982-221610982,hs1:240336663-240336663;hs1:222510946-222510946,hs1:241471857-241471857;hs1:226497591-226497591,hs1:165076945-165076945;hs1:226561606-226561606,hs1:206272659-206272659;hs1:227469535-227469535,hs1:196658686-196658686;hs1:227782654-227782654,hs1:227547446-227547446;hs1:229632434-229632434,hs1:153174214-153174214;hs1:230392560-230392560,hs1:146719451-146719451;hs1:232037074-232037074,hs1:243578878-243578878;hs1:232317217-232317217,hs1:208040318-208040318;hs1:234280579-234280579,hs1:220409874-220409874;hs1:234487961-234487961,hs1:173835909-173835909;hs1:235841129-235841129,hs1:237580068-237580068;hs1:242761494-242761494,hs1:189254341-189254341;hs1:245172709-245172709,hs1:193598317-193598317;hs1:246026360-246026360,hs1:188830278-188830278;hs1:248318267-248318267,hs1:193549573-193549573;hs11:116595859-116595859,hs11:120900807-120900807;hs11:120884215-120884215,hs11:122150331-122150331;hs18:48198026-48198026,hs4:54769265-54769265;hs2:42035919-42035919,hs5:58684453-58684453;hs2:192440470-192440470,hs11:56401950-56401950;hs20:26220634-26220634,hs19:33444268-33444268;hs21:38472500-38472500,hs5:165406325-165406325;hs3:22107821-22107821,hs9:88214033-88214033;hs5:94059708-94059708,hs1:75213827-75213827;hs6:65458491-65458491,hs6:65456526-65456526 ADAMTS2;ADAR;AGTPBP1;AHCTF1;ARID4B;ARNT;ATP2B4;AXDND1;C1orf186;C1orf31;C1orf98;CACNA1E;CD34;CDC42BPA;CDC73;CEP170;CEP89;CFH;CHD1L;CNNM1;CNTN2;DDR2;DISC1;DUSP12;DYRK3;EFCAB2;ENSA;EPHX1;EYS;FAM168A;FAM20B;FMN2;GALNT2;GAS5;HMCN1;IGSF9;IL19;IL6R;ILDR2;KCNH1;KCNT2;KCTD3;KDM5B;KIAA1383;KIF26B;LAMC1;LEMD1;LMX1A;LOC100130331;LOC100289211;LOC643723;LYST;MAPK4;MARK1;MCTP1;MIR548F1;NAV1;NCAPD3;NME7;NOS1AP;NR5A2;NUP133;OPN3;OR2L13;OR8U8;PARP1;PBX1;PDE4D;PIK3C2B;PKP1;PLD5;PM20D1;POLD3;PPP2R5A;PRRC2C;RAB3GAP2;RAB4A;RABGAP1L;RASAL2;RGS21;RGS7;RIT1;RNU5F-1;ROBO3;RPRD2;RYR2;SDCCAG8;SDHC;SLC35F3;SLC45A2;SMG7;SMYD3;SNX27;SUSD4;TAF1A;TBCEL;THEM4;TTC3;TYW3;UCHL5;USH2A;VAMP4;VPS45;XPR1;ZBTB37;ZNF618;ZNF678 Pfizer Oncology, San Diego, CA, USA Elucidating the molecular basis of hepatocellular carcinoma (HCC) is crucial to developing targeted diagnostics and therapies for this deadly disease. The landscape of somatic genomic rearrangements (GRs), which can lead to oncogenic gene fusions, remains poorly characterized in HCC. We have predicted 4314 GRs including large-scale insertions, deletions, inversions and translocations based on the whole-genome sequencing data for 88 primary HCC tumor/non-tumor tissues. We identified chromothripsis in 5 HCC genomes (5.7%) recurrently affecting chromosomal arms 1q and 8q. Albumin (ALB) was found to harbor GRs, deactivating mutations and deletions in 10% of cohort. Integrative analysis identified a pattern of paired intra-chromosomal translocations flanking focal amplifications and asymmetrical patterns of copy number variation flanking breakpoints of translocations. Furthermore, we predicted 260 gene fusions which frequently result in aberrant over-expression of the 3' genes in tumors and validated 18 gene fusions, including recurrent fusion (2/88) of ABCB11 and LRP2. GRCh37/hg19 GSE25097 ERP001196 Yes AHCTF1,OPN3;AXDND1,RGS21;CD34,NR5A2;CDC42BPA,CFH;DDR2,RIT1;LAMC1,PBX1;LEMD1,THEM4;LOC100289211,DISC1;LYST,RYR2;MCTP1,TYW3;PLD5,IL19;PRRC2C,ZBTB37;RAB3GAP2,SLC35F3;RAB4A,SNX27;RABGAP1L,RASAL2;UCHL5,SUSD4;USH2A,ARNT CTDB0004 Research 24462510 Julio Fernandez-Banet, Nikki P. Lee, Kin Tak Chan, Huan Gao, Xiao Liu, Wing-Kin Sung,Winnie Tan, Sheung Tat Fan, Ronnie T. Poon, Shiyong Li, Keith Ching, Paul A. Rejto, Mao Mao, Zhengyan Kan Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma Genomics 2014 Jan 6,8,13 Hepatocellular carcinoma Next Generation Sequencing Homo sapiens 39T Illumina HiSeq 2000 chr12:24645563-24738879:1;chr12:78169609-88786765:1;chr13:23912324-80201009:1;chr13:24443145-80055872:-1;chr13:65105106-66024797:-1;chr13:65939359-81547930:1;chr13:67613309-80940102:-1;chr13:79973005-80575107:-1;chr15:101236855-101240400:-1;chr15:61676817-61747812:-1;chr18:55243248-55251507:-1;chr1:12558131-12558872:-1;chr1:223588075-223655247:-1;chr20:42848008-42848137:1;chr2:125777393-164375256:-1;chr2:31558963-40628785:1;chr3:158988279-159870359:-1;chr6:33505941-40678634:1;chr6:35648993-40896804:-1;chr6:37384613-45069916:-1;chr6:40904604-40906513:1;chr6:41991234-42958247:-1;chr6:80825114-80825236:1;chr7:13697734-26238926:-1;chr8:10234784-11761656:-1;chr8:105320972-105659217:-1;chr8:105525208-117004096:-1;chr8:113771527-114762074:-1;chr8:113932031-114766291:1;chr8:114762169-114874375:-1;chr8:114785424-115394094:1;chr8:115323285-143937031:1;chr8:135318272-142160228:1;chr8:4588141-26742571:1;chr8:77924322-113737213:-1;chr8:96560827-108645368:-1 hs1:189940250-189940250,hs1:189953149-189953149;hs1:196679980-196679980,hs8:113109783-113109783;hs1:231932112-231932112,hs2:204851845-204851845;hs1:248324102-248324102,hs1:248518578-248518578;hs1:248436061-248436061,hs1:248218582-248218582;hs13:24303841-24303841,hs15:61664000-61664000;hs13:26867891-26867891,hs13:65652586-65652586;hs13:26870274-26870274,hs13:81128755-81128755;hs13:64573583-64573583,hs13:80434629-80434629;hs13:64583126-64583126,hs16:81911913-81911913;hs13:65652518-65652518,hs13:23914529-23914529;hs13:65939451-65939451,hs16:80340949-80340949;hs13:65988378-65988378,hs13:81576181-81576181;hs13:79972927-79972927,hs13:64575180-64575180;hs13:79979513-79979513,hs13:65178178-65178178;hs13:80050432-80050432,hs13:80050486-80050486;hs13:80205805-80205805,hs13:24410396-24410396;hs13:80316638-80316638,hs13:80154870-80154870;hs13:80434702-80434702,hs13:24413912-24413912;hs13:80550064-80550064,hs13:80933817-80933817;hs13:81537261-81537261,hs13:80316551-80316551;hs13:81545032-81545032,hs13:81587298-81587298;hs13:81582445-81582445,hs13:79899143-79899143;hs13:81612188-81612188,hs13:24301682-24301682;hs15:61539678-61539678,hs15:61548443-61548443;hs15:61591460-61591460,hs13:64502324-64502324;hs15:61727064-61727064,hs13:25553931-25553931;hs16:80151163-80151163,hs13:80380806-80380806;hs2:111440809-111440809,hs2:183197424-183197424;hs2:183668080-183668080,hs2:183653531-183653531;hs2:183694977-183694977,hs6:46515027-46515027;hs4:153834036-153834036,hsM:14100-14100;hs6:7276363-7276363,hs17:9269015-9269015;hs6:36093582-36093582,hs6:45878184-45878184;hs6:36968553-36968553,hs11:101860408-101860408;hs6:38077296-38077296,hs6:38079360-38079360;hs6:40846035-40846035,hs6:40972867-40972867;hs6:40896748-40896748,hs6:40888377-40888377;hs6:40898405-40898405,hs1:223656150-223656150;hs6:40900111-40900111,hs6:40901312-40901312;hs6:40901675-40901675,hs6:40904967-40904967;hs6:40901675-40901675,hs6:40904968-40904968;hs6:41331902-41331902,hs6:35802864-35802864;hs6:41958640-41958640,hs6:40707988-40707988;hs6:45076739-45076739,hs6:39788433-39788433;hs6:46527072-46527072,hs6:46528998-46528998;hs6:57624207-57624207,hs6:57620145-57620145;hs6:112243271-112243271,hs22:24195877-24195877;hs8:77980613-77980613,hs8:77557676-77557676;hs8:98170895-98170895,hs8:105237233-105237233;hs8:105239259-105239259,hs8:98168374-98168374;hs8:105953917-105953917,hs8:117005433-117005433;hs8:110328750-110328750,hs8:105211082-105211082;hs8:111541912-111541912,hs8:114361923-114361923;hs8:111633152-111633152,hs8:113219005-113219005;hs8:112615866-112615866,hs8:114353024-114353024;hs8:112617449-112617449,hs8:113222570-113222570;hs8:112741096-112741096,hs8:96550449-96550449;hs8:113300228-113300228,hs8:113399774-113399774;hs8:113763157-113763157,hs8:113219003-113219003;hs8:113764541-113764541,hs8:113770774-113770774;hs8:113810966-113810966,hs8:113390335-113390335;hs8:113811794-113811794,hs8:114879628-114879628;hs8:114762149-114762149,hs8:113202250-113202250;hs8:114784427-114784427,hs8:113525004-113525004;hs8:114801509-114801509,hs8:113810997-113810997;hs8:114801509-114801509,hs8:113810990-113810990;hs8:115422856-115422856,hs8:113419285-113419285;hsY:4972219-4972219,hsY:7366508-7366508 BCKDHB;CCND3;CDK8;CFH;CLIC5;CSMD1;CSMD3;CYP39A1;DAAM2;DENND3;FECH;FKBP5;HNRNPA2B1;IQCJ-SCHIP1;KIAA1377;LOC100192378;LOC100505783;LOC100616530;LRP12;MIPEP;MSRA;NDFIP2;NUDCD1;OR2L13;PCDH11Y;PCDH9;PDE1A;PLCG2;PPP2R5D;RBM26;RIMS2;SACS;SLC8A1;SOX5;SRPK1;STX8;SUPT3H;TSNAX-DISC1;VPS13D;XDH;ZFAND3 Pfizer Oncology, San Diego, CA, USA Elucidating the molecular basis of hepatocellular carcinoma (HCC) is crucial to developing targeted diagnostics and therapies for this deadly disease. The landscape of somatic genomic rearrangements (GRs), which can lead to oncogenic gene fusions, remains poorly characterized in HCC. We have predicted 4314 GRs including large-scale insertions, deletions, inversions and translocations based on the whole-genome sequencing data for 88 primary HCC tumor/non-tumor tissues. We identified chromothripsis in 5 HCC genomes (5.7%) recurrently affecting chromosomal arms 1q and 8q. Albumin (ALB) was found to harbor GRs, deactivating mutations and deletions in 10% of cohort. Integrative analysis identified a pattern of paired intra-chromosomal translocations flanking focal amplifications and asymmetrical patterns of copy number variation flanking breakpoints of translocations. Furthermore, we predicted 260 gene fusions which frequently result in aberrant over-expression of the 3' genes in tumors and validated 18 gene fusions, including recurrent fusion (2/88) of ABCB11 and LRP2. GRCh37/hg19 GSE25097 ERP001196 Yes NUDCD1,RIMS2;SUPT3H,DAAM2;XDH,SLC8A1 CTDB0005 Research 24462510 Julio Fernandez-Banet, Nikki P. Lee, Kin Tak Chan, Huan Gao, Xiao Liu, Wing-Kin Sung,Winnie Tan, Sheung Tat Fan, Ronnie T. Poon, Shiyong Li, Keith Ching, Paul A. Rejto, Mao Mao, Zhengyan Kan Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma Genomics 2014 Jan 4,8 Hepatocellular carcinoma Next Generation Sequencing Homo sapiens 64T Illumina HiSeq 2000 chr11:81895173-81911689:-1;chr12:100380237-100380309:1;chr14:106465634-106465776:-1;chr16:71944843-72006656:1;chr19:34673545-34709430:-1;chr1:215839087-215841241:-1;chr1:239438785-239633471:-1;chr2:11932745-11933488:1;chr3:193693498-193711106:-1;chr4:102549929-172081640:1;chr4:103409918-124865736:-1;chr4:106592727-170879794:1;chr4:109495142-174565906:-1;chr4:109495203-146836679:1;chr4:109565065-131888870:-1;chr4:111356876-174566198:1;chr4:113579060-124869332:1;chr4:121603891-125359396:1;chr4:124869276-175779672:1;chr4:132387940-146109529:1;chr4:147217604-175456604:-1;chr4:156397009-170879851:-1;chr4:172086657-178228788:-1;chr4:174566176-185501895:1;chr5:105255679-105258762:1;chr6:40965786-40965834:-1;chr7:41670302-41671109:-1;chr8:103195676-133607161:-1;chr8:103597286-103777796:-1;chr8:114439123-130455247:1;chr8:116385448-136103421:-1;chr8:117859836-118936351:1;chr8:122849206-129962339:1;chr8:124332270-125052786:-1;chr8:128894210-130370996:-1;chr8:129521077-135933749:-1;chr8:134777811-135512849:-1;chr8:137370708-138347859:-1;chr8:37876634-43614284:-1;chr8:48261425-49309404:1;chr8:48547636-49746817:-1;chr8:56847967-56952661:-1;chr8:65089340-75699428:-1;chr8:74072815-137398911:1;chr8:75492808-77422181:-1;chr8:77421600-91690139:-1;chr8:79228371-81714172:1;chr8:95027444-117688871:-1;chr8:98797220-127675980:-1;chr8:99718262-125906991:1;chr9:135687892-135687950:1 hs1:36303339-36303339,hs1:36281525-36281525;hs2:164288513-164288513,hs14:82326148-82326148;hs4:106021401-106021401,hs4:150134375-150134375;hs4:143752099-143752099,hs4:136925771-136925771;hs4:172461695-172461695,hs4:147039565-147039565;hs4:174566383-174566383,hs4:147217604-147217604;hs8:56490078-56490078,hs8:37726767-37726767;hs8:68724742-68724742,hs8:68728980-68728980;hs8:69855876-69855876,hs8:69853896-69853896;hs8:77582980-77582980,hs8:80242614-80242614;hs8:77861557-77861557,hs8:77862675-77862675;hs8:79323100-79323100,hs8:79546151-79546151;hs8:79323411-79323411,hs8:79323674-79323674;hs8:101095006-101095006,hs8:134405629-134405629;hs8:101717551-101717551,hs8:131949480-131949480;hs8:103002232-103002232,hs8:131946810-131946810;hs8:103112358-103112358,hs10:901103-901103;hs8:103245907-103245907,hs8:118855185-118855185;hs8:103586116-103586116,hs8:103586304-103586304;hs8:103778146-103778146,hs8:117937970-117937970;hs8:104332473-104332473,hs8:104333412-104333412;hs8:116201762-116201762,hs8:103095381-103095381;hs8:118867203-118867203,hs8:118865816-118865816;hs8:119143960-119143960,hs10:900860-900860;hs8:127012676-127012676,hs8:99186903-99186903;hs8:129961177-129961177,hs8:129694309-129694309;hs8:130381233-130381233,hs8:126390246-126390246;hs8:130390627-130390627,hs8:98846696-98846696;hs8:130461838-130461838,hs8:136239100-136239100;hs8:131583499-131583499,hs8:130381878-130381878;hs8:133409994-133409994,hs8:138635123-138635123;hs8:135719141-135719141,hs8:136228459-136228459;hs8:136103597-136103597,hs8:136104889-136104889;hs8:137172350-137172350,hs8:94648196-94648196;hs10:900860-900860,hs8:119143960-119143960;hs10:11382639-11382639,hs8:130365555-130365555;hs10:11740121-11740121,hs10:11741973-11741973;hs10:12301195-12301195,hs10:1059278-1059278;hs11:12316286-12316286,hs1:31033224-31033224;hs12:106109871-106109871,hs1:27064182-27064182;hs16:13956409-13956409,hs9:79921336-79921336;hs16:32146478-32146478,hs16:26669738-26669738;hs19:18099404-18099404,hs19:18097016-18097016;hs19:18807594-18807594,hs19:18818887-18818887;hs19:19561653-19561653,hs19:19562727-19562727;hs19:19611425-19611425,hs19:19614380-19614380;hs19:19655285-19655285,hs19:19657425-19657425;hs19:21085362-21085362,hs19:21084072-21084072;hs21:23284828-23284828,hs7:46116145-46116145 ADCY8;AK8;ARHGEF38;ARID1A;ATAD2;CILP2;CRTC1;CSMD3;EIF2C4;EIF3H;EXT1;FER1L6;FZD6;GATAD2A;GTPBP4;INPP4B;IST1;KCNN1;KCNQ3;KIAA0146;LAPTM4B;LARP4B;LOC100192378;LOC100505545;LOC100505718;LOC100506085;LOC285456;LOC642924;LOC647323;LPIN1;LRRC6;LSM14A;LYN;MICALCL;NCALD;PABPC1;PKD1L3;PVT1;RAB11FIP1;RAD21;RGS22;RRM2B;SLC10A7;STK3;USH2A;VPS13A;ZFAT;ZNF704;ZNF827 Pfizer Oncology, San Diego, CA, USA Elucidating the molecular basis of hepatocellular carcinoma (HCC) is crucial to developing targeted diagnostics and therapies for this deadly disease. The landscape of somatic genomic rearrangements (GRs), which can lead to oncogenic gene fusions, remains poorly characterized in HCC. We have predicted 4314 GRs including large-scale insertions, deletions, inversions and translocations based on the whole-genome sequencing data for 88 primary HCC tumor/non-tumor tissues. We identified chromothripsis in 5 HCC genomes (5.7%) recurrently affecting chromosomal arms 1q and 8q. Albumin (ALB) was found to harbor GRs, deactivating mutations and deletions in 10% of cohort. Integrative analysis identified a pattern of paired intra-chromosomal translocations flanking focal amplifications and asymmetrical patterns of copy number variation flanking breakpoints of translocations. Furthermore, we predicted 260 gene fusions which frequently result in aberrant over-expression of the 3' genes in tumors and validated 18 gene fusions, including recurrent fusion (2/88) of ABCB11 and LRP2. GRCh37/hg19 GSE25097 ERP001196 Yes FER1L6-AS1,ATAD2;LARP4B,NCALD;LOC285456,ZNF827;RAD21,EXT1 CTDB0006 Research 24462510 Julio Fernandez-Banet, Nikki P. Lee, Kin Tak Chan, Huan Gao, Xiao Liu, Wing-Kin Sung,Winnie Tan, Sheung Tat Fan, Ronnie T. Poon, Shiyong Li, Keith Ching, Paul A. Rejto, Mao Mao, Zhengyan Kan Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma Genomics 2014 Jan 5,6,8 Hepatocellular carcinoma Next Generation Sequencing Homo sapiens 172T Illumina HiSeq 2000 chr10:10051003-10052023:1;chr11:41512269-41733251:1;chr11:88223296-88228599:1;chr12:92625984-92627496:1;chr13:94471716-94967268:1;chr14:35009793-36335438:1;chr14:45077719-45084845:1;chr15:89972297-89972392:1;chr17:63340100-63356474:1;chr18:2365198-2366710:1;chr18:23937090-23937284:1;chr18:26455189-26455568:1;chr18:27107918-27110932:1;chr18:8534188-8550686:1;chr20:14837336-15068900:1;chr21:38898415-38903014:1;chr21:40789981-40790716:1;chr2:1865608-1865769:1;chr2:44435710-44598872:1;chr2:55935032-56004654:1;chr2:57031863-57032517:1;chr3:100097590-100150293:1;chr3:188304251-188556373:1;chr3:237018-237452:1;chr3:59804088-59804159:1;chr3:9375294-9491177:1;chr4:138014618-141690684:1;chr4:2429134-2429236:1;chr4:42592600-42592708:1;chr5:10213227-10213392:1;chr5:11015881-11019157:1;chr5:11564826-14457566:1;chr5:12543675-12544226:1;chr5:1396087-1616608:1;chr5:14189219-14809528:1;chr5:14220006-19542336:1;chr5:14334754-23640791:1;chr5:1477839-22967118:1;chr5:1622046-5767200:1;chr5:16571082-28963504:1;chr5:180044484-180045491:1;chr5:19563981-23546575:1;chr5:23597185-23720076:1;chr5:305672-10355780:1;chr5:464224-10255486:1;chr5:4893853-24001982:1;chr5:5328131-5862262:1;chr5:5663477-13320272:1;chr5:5758896-23718587:1;chr5:6755464-19607989:1;chr5:7886969-14827491:1;chr5:795023-1543664:1;chr5:8443743-9062774:1;chr5:9080504-22968161:1;chr6:11618091-11777956:1;chr6:43532095-43535523:1;chr6:5449672-5454059:1;chr6:5458546-6111528:1;chr6:5462364-11699345:1;chr6:5468965-7835514:1;chr6:5956210-11695773:1;chr6:5956210-11695823:1;chr6:6107798-7872067:1;chr6:6340781-11781130:1;chr6:65440058-67675963:1;chr6:7917744-11779800:1;chr8:17440427-30390723:1;chr8:18105994-29827622:1;chr8:23943758-29423238:1;chr8:30321556-30322484:1;chr8:38023193-39300280:1;chr8:70728634-140423708:1;chr8:73298385-125801646:1;chr9:114358123-114398971:1;chrX:19848352-20220688:1;chrX:39125286-39126165:1;chrX:76085104-76085876:1;chrX:96343876-96344599:1 hs10:32936400-32936400,hs1:171667047-171667047;hs10:50262499-50262499,hs6:134043724-134043724;hs11:18920395-18920395,hs11:18919178-18919178;hs11:18979009-18979009,hs11:18981385-18981385;hs11:98229200-98229200,hs11:123802464-123802464;hs11:123802223-123802223,hs11:98229225-98229225;hs13:54689582-54689582,hs5:26511-26511;hs14:38975592-38975592,hs14:38972823-38972823;hs14:86463888-86463888,hs6:38300981-38300981;hs17:28721365-28721365,hs17:28555875-28555875;hs17:45721478-45721478,hsX:39125375-39125375;hs18:50513688-50513688,hs18:27068052-27068052;hs19:19165634-19165634,hs19:19163503-19163503;hs5:26527-26527,hs13:54689564-54689564;hs5:253701-253701,hs5:16540536-16540536;hs5:671403-671403,hs5:256527-256527;hs5:2334545-2334545,hs5:4506713-4506713;hs5:5856154-5856154,hs5:5753910-5753910;hs5:5877309-5877309,hs5:8439829-8439829;hs5:5888559-5888559,hs5:6450687-6450687;hs5:6753770-6753770,hs5:6784796-6784796;hs5:6784791-6784791,hs5:6784605-6784605;hs5:6964269-6964269,hs5:16900080-16900080;hs5:7654115-7654115,hs5:15283661-15283661;hs5:7656828-7656828,hs5:5945436-5945436;hs5:9465754-9465754,hs5:6602002-6602002;hs5:11565776-11565776,hs5:20231496-20231496;hs5:13316329-13316329,hs5:9462770-9462770;hs5:14456164-14456164,hs5:16098130-16098130;hs5:15288863-15288863,hs5:14843739-14843739;hs5:19179321-19179321,hs5:1402045-1402045;hs5:19247108-19247108,hs5:28368087-28368087;hs5:23570650-23570650,hs5:6018136-6018136;hs5:23604532-23604532,hs5:5767990-5767990;hs5:28369940-28369940,hs5:1544551-1544551;hs5:61454023-61454023,hs5:61449963-61449963;hs6:5449718-5449718,hs6:5450171-5450171;hs6:5465398-5465398,hs6:6350653-6350653;hs6:6106984-6106984,hs6:11616666-11616666;hs6:6106984-6106984,hs6:11616641-11616641;hs6:6106984-6106984,hs6:11616654-11616654;hs6:6342063-6342063,hs6:11825975-11825975;hs6:6351984-6351984,hs6:6343180-6343180;hs6:7875083-7875083,hs6:5462722-5462722;hs6:7893933-7893933,hs6:11790612-11790612;hs6:11559755-11559755,hs6:5468543-5468543;hs6:11560346-11560346,hs6:11828899-11828899;hs6:11616666-11616666,hs6:6106982-6106982;hs6:11784151-11784151,hs6:5450260-5450260;hs6:11793320-11793320,hs6:6111850-6111850;hs6:37615498-37615498,hs6:37597857-37597857;hs6:38300981-38300981,hs14:86463888-86463888;hs6:43495270-43495270,hs6:43489493-43489493;hs6:43984615-43984615,hs6:43987113-43987113;hs6:53494861-53494861,hs6:53495420-53495420;hs6:98473392-98473392,hs6:98473565-98473565;hs6:99000252-99000252,hs6:83983758-83983758;hs6:100946081-100946081,hs6:83982749-83982749;hs8:4686344-4686344,hs8:61983099-61983099;hs8:30044559-30044559,hs8:30130426-30130426;hs8:36661291-36661291,hs8:36639876-36639876;hs8:72164328-72164328,hs8:90634225-90634225;hs8:75136267-75136267,hs8:75138504-75138504;hs8:90634247-90634247,hs8:72164440-72164440;hsX:39125377-39125377,hs17:45721476-45721476 ADCY2;AHRR;ANKH;ARMC6;ATP8A1;BMP6;BRMS1L;BTBD9;C10orf68;C6orf105;CAMKMT;CCT5;CDH18;CPD;CSMD1;CTNND2;DCC;DIAPH2;DNAJC25;EXOC3;EYA1;EYS;FAM134B;FARS2;FHIT;FLT4;GPC6;KCNU1;LCA5L;LNP1;LOC402160;LOC728613;LOC729506;LPCAT1;LPP;LSM1;LY86-AS1;MACROD2;MDGA1;ME1;MIR548O2;MTRR;MUTED-TXNDC5;MYO10;MYT1L;NSUN2;PAPD7;PDGFRL;PPM1B;PTGR1;RBPMS;RPS6KA3;SDHA;SEMA5A;SETD5;SH3KBP1;SLC6A3;SLC6A4;SLCO5A1;TAF4B;TMEM170B;TOMM70A;TPPP;TRIO;UBE2QL1;VSTM4;XPO5 Pfizer Oncology, San Diego, CA, USA Elucidating the molecular basis of hepatocellular carcinoma (HCC) is crucial to developing targeted diagnostics and therapies for this deadly disease. The landscape of somatic genomic rearrangements (GRs), which can lead to oncogenic gene fusions, remains poorly characterized in HCC. We have predicted 4314 GRs including large-scale insertions, deletions, inversions and translocations based on the whole-genome sequencing data for 88 primary HCC tumor/non-tumor tissues. We identified chromothripsis in 5 HCC genomes (5.7%) recurrently affecting chromosomal arms 1q and 8q. Albumin (ALB) was found to harbor GRs, deactivating mutations and deletions in 10% of cohort. Integrative analysis identified a pattern of paired intra-chromosomal translocations flanking focal amplifications and asymmetrical patterns of copy number variation flanking breakpoints of translocations. Furthermore, we predicted 260 gene fusions which frequently result in aberrant over-expression of the 3' genes in tumors and validated 18 gene fusions, including recurrent fusion (2/88) of ABCB11 and LRP2. GRCh37/hg19 GSE25097 ERP001196 Yes C6orf105,MUTED-TXNDC5;CAMKMT,PPM1B;CPD,SLC6A4;EXOC3,CCT5;FARS2,BMP6;FARS2,LY86-AS1;LOC729506,SEMA5A;MARCH6,PDCD6;RBPMS,PDGFRL;RPS6KA3,SH3KBP1;SDHA,FAM134B;SLC6A3,LOC728613;TPPP,SDHA;TRIO,MARCH11 CTDB0009 Research 23550136 Jonathan J. M. Landry, Paul Theodor Pyl, Tobias Rausch, Thomas Zichner, Manu M. Tekkedil, Adrian M. Stutz, Anna Jauch, Raeka S. Aiyar, Gregoire Pau, Nicolas Delhomme, Julien Gagneur, Jan O. Korbel, Wolfgang Huber, Lars M. Steinmetz The Genomic and Transcriptomic Landscape of a HeLa Cell Line G3 (Bethesda) 2013 Mar 5,11,19,X Cervical cancer Next Generation Sequencing Homo sapiens 23550136_1 Illumina HiSeq 2000 European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany, and University Hospital Heidelberg, Institute of Human Genetics, 69120 Heidelberg, Germany HeLa is the most widely used model cell line for studying human cellular and molecular biology. To date, no genomic reference for this cell line has been released, and experiments have relied on the human reference genome. Effective design and interpretation of molecular genetic studies performed using HeLa cells require accurate genomic information. Here we present a detailed genomic and transcriptomic characterization of a HeLa cell line. We performed DNA and RNA sequencing of a HeLa Kyoto cell line and analyzed its mutational portfolio and gene expression profile. Segmentation of the genome according to copy number revealed a remarkably high level of aneuploidy and numerous large structural variants at unprecedented resolution. Some of the extensive genomic rearrangements are indicative of catastrophic chromosome shattering, known as chromothripsis. Our analysis of the HeLa gene expression profile revealed that several pathways, including cell cycle and DNA repair, exhibit significantly different expression patterns from those in normal human tissues. Our results provide the first detailed account of genomic variants in the HeLa genome, yielding insight into their impact on gene expression and cellular function as well as their origins. This study underscores the importance of accounting for the strikingly aberrant characteristics of HeLa cells when designing and interpreting experiments, and has implications for the use of HeLa as a model of human biology. GRCh37/hg19 phs000643 Yes NA CTDB0010 Research 23699601 Ryan D. Morin, Karen Mungall, Erin Pleasance, Andrew J. Mungall, Rodrigo Goya, Ryan D. Huff, David W. Scott, Jiarui Ding, Andrew Roth, Readman Chiu, Richard D. Corbett, Fong Chun Chan, Maria Mendez-Lago, Diane L. Trinh, Madison Bolger-Munro, Greg Taylor, Alireza Hadj Khodabakhshi, Susana Ben-Neriah, Julia Pon, Barbara Meissner, Bruce Woolcock, Noushin Farnoud, Sanja Rogic, Emilia L. Lim, Nathalie A. Johnson, Sohrab Shah, Steven Jones, Christian Steidl, Robert Holt, Inanc Birol, Richard Moore, Joseph M. Connors, Randy D. Gascoyne, Marco A. Marra Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing Blood 2013 Aug 2 Diffuse large B-cell lymphoma Next Generation Sequencing Homo sapiens RG014 Illumina HiSeq 2000 chr11:5741151-5765859:-1;chr12:65705844-65860964:1;chr12:81020356-81057622:1;chr2:170199813-170326345:-1;chr2:57315075-77261648:-1;chr2:58945897-64101169:1;chr2:59398168-62198357:1;chr2:61030770-64950932:1;chr2:61603741-64186434:1;chr2:61959737-65021132:-1;chr2:64107369-83051955:1;chr2:64110075-65196092:1;chr2:64113324-65011399:-1;chr2:65060073-83052605:1;chr2:79181777-83926268:-1;chr6:76460862-77861329:-1;chr6:76957466-76993247:1;chr8:129070957-129271216:1 hs17:25765380-25765380,hs2:176675354-176675354;hs17:48938937-48938937,hs2:119668564-119668564;hs17:48922187-48922187,hs2:119665556-119665556;hs2:35595408-35595408,hs2:117065447-117065447;hs2:82171889-82171889,hs2:83807361-83807361;hs2:79094169-79094169,hs2:83058298-83058298;hs2:60090711-60090711,hs2:62199561-62199561;hs2:65279526-65279526,hs2:65287675-65287675;hs2:64079006-64079006,hs2:64192609-64192609;hs2:77936878-77936878,hs2:84222375-84222375;hs2:83398215-83398215,hs6:136004781-136004781;hs2:60450993-60450993,hs2:60495932-60495932;hs2:83700519-83700519,hs2:84985328-84985328;hs2:61026746-61026746,hs2:65237642-65237642;hs2:64077491-64077491,hs2:65019980-65019980;hs2:60485726-60485726,hs2:61960697-61960697;hs4:43228837-43228837,hs17:49888087-49888087;hs6:75376489-75376489,hs6:76456545-76456545;hs6:75942261-75942261,hs6:76460877-76460877;hs6:41494848-41494848,hs6:69619654-69619654;hs6:75965673-75965673,hs6:118982169-118982169 Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention. NCBI 36/hg18 phs000532 Yes NA CTDB0011 Research 23699601 Ryan D. Morin, Karen Mungall, Erin Pleasance, Andrew J. Mungall, Rodrigo Goya, Ryan D. Huff, David W. Scott, Jiarui Ding, Andrew Roth, Readman Chiu, Richard D. Corbett, Fong Chun Chan, Maria Mendez-Lago, Diane L. Trinh, Madison Bolger-Munro, Greg Taylor, Alireza Hadj Khodabakhshi, Susana Ben-Neriah, Julia Pon, Barbara Meissner, Bruce Woolcock, Noushin Farnoud, Sanja Rogic, Emilia L. Lim, Nathalie A. Johnson, Sohrab Shah, Steven Jones, Christian Steidl, Robert Holt, Inanc Birol, Richard Moore, Joseph M. Connors, Randy D. Gascoyne, Marco A. Marra Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing Blood 2013 Aug 1,2,9,17 Diffuse large B-cell lymphoma Next Generation Sequencing Homo sapiens RG028 Illumina HiSeq 2000 chr10:119070367-121619306:-1;chr11:35141779-35165434:-1;chr14:36701359-36840978:-1;chr14:72625917-72666602:-1;chr17:21644130-22782616:1;chr17:40668478-40735550:-1;chr18:51225332-51298777:-1;chr19:7005812-14457285:1;chr1:1297525-1346091:-1;chr1:152467650-152471574:-1;chr2:146440464-148588487:-1;chr3:189003121-189799358:-1;chr6:30004458-30022379:-1;chr6:31200494-32919822:-1;chr9:21854346-21958850:-1 hs1:56808946-56808946,hs6:106644529-106644529;hs1:56808986-56808986,hs6:106644512-106644512;hs1:204432648-204432648,hs1:210243172-210243172;hs17:24009064-24009064,hs17:36056640-36056640;hs19:54622010-54622010,hs19:63789465-63789465;hs19:62436306-62436306,hs2:146408009-146408009;hs2:113889788-113889788,hs4:191114592-191114592;hs4:49021102-49021102,hs1:141547959-141547959;hsX:136261018-136261018,hsX:153961240-153961240 Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention. NCBI 36/hg18 phs000532 Yes NA CTDB0012 Research 23699601 Ryan D. Morin, Karen Mungall, Erin Pleasance, Andrew J. Mungall, Rodrigo Goya, Ryan D. Huff, David W. Scott, Jiarui Ding, Andrew Roth, Readman Chiu, Richard D. Corbett, Fong Chun Chan, Maria Mendez-Lago, Diane L. Trinh, Madison Bolger-Munro, Greg Taylor, Alireza Hadj Khodabakhshi, Susana Ben-Neriah, Julia Pon, Barbara Meissner, Bruce Woolcock, Noushin Farnoud, Sanja Rogic, Emilia L. Lim, Nathalie A. Johnson, Sohrab Shah, Steven Jones, Christian Steidl, Robert Holt, Inanc Birol, Richard Moore, Joseph M. Connors, Randy D. Gascoyne, Marco A. Marra Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing Blood 2013 Aug 6,9,13,15,18 Diffuse large B-cell lymphoma Next Generation Sequencing Homo sapiens RG034 Illumina HiSeq 2000 chr11:89591175-89603940:-1;chr19:10201579-10243189:-1;chr3:116907103-117124779:1;chr3:30882610-32919140:1;chr4:27509942-27522063:1;chr6:32556135-32787998:1;chr9:73648796-135984683:-1;chr9:74010545-122137819:1;chr9:74012466-135928486:-1 hs1:7917554-7917554,hs2:212411334-212411334;hs1:211480185-211480185,hs1:233469225-233469225;hs1:211480438-211480438,hs1:233470458-233470458;hs12:59079221-59079221,hs3:104717848-104717848;hs13:19333012-19333012,hs6:58448015-58448015;hs13:74231050-74231050,hs6:148187364-148187364;hs15:43161536-43161536,hs15:44265431-44265431;hs18:99044-99044,hsX:29179265-29179265;hs18:3223258-3223258,hs7:31794203-31794203;hs18:35202776-35202776,hs18:35963496-35963496;hs18:38646689-38646689,hs9:72929765-72929765;hs18:55281977-55281977,hs9:100213501-100213501;hs18:58944466-58944466,hs14:105453750-105453750;hs18:60448528-60448528,hs9:80921411-80921411;hs18:60448860-60448860,hs9:80920106-80920106;hs4:19855480-19855480,hs5:160965636-160965636;hs4:114010531-114010531,hs8:135704572-135704572;hs9:29523040-29523040,hs13:64616941-64616941;hs9:68504374-68504374,hs9:135678585-135678585;hs9:87562349-87562349,hs9:135983249-135983249;hsX:27045422-27045422,hs2:64728521-64728521 Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention. NCBI 36/hg18 phs000532 Yes NA CTDB0013 Research 23699601 Ryan D. Morin, Karen Mungall, Erin Pleasance, Andrew J. Mungall, Rodrigo Goya, Ryan D. Huff, David W. Scott, Jiarui Ding, Andrew Roth, Readman Chiu, Richard D. Corbett, Fong Chun Chan, Maria Mendez-Lago, Diane L. Trinh, Madison Bolger-Munro, Greg Taylor, Alireza Hadj Khodabakhshi, Susana Ben-Neriah, Julia Pon, Barbara Meissner, Bruce Woolcock, Noushin Farnoud, Sanja Rogic, Emilia L. Lim, Nathalie A. Johnson, Sohrab Shah, Steven Jones, Christian Steidl, Robert Holt, Inanc Birol, Richard Moore, Joseph M. Connors, Randy D. Gascoyne, Marco A. Marra Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing Blood 2013 Aug 1 Diffuse large B-cell lymphoma Next Generation Sequencing Homo sapiens RG043 Illumina HiSeq 2000 chr11:48324097-48330277:-1;chr11:5741151-5765859:-1;chr11:5741151-5765859:-1;chr1:12250777-193382205:-1;chr1:213285864-213354216:-1;chr1:228454814-228632682:-1 hs1:6929266-6929266,hs1:223002855-223002855;hs1:9608555-9608555,hs1:17082878-17082878;hs1:16411862-16411862,hs1:204052851-204052851;hs1:41088909-41088909,hs1:211452286-211452286;hs1:193508150-193508150,hs1:197311616-197311616;hs1:209387883-209387883,hs1:215984986-215984986;hs18:58938257-58938257,hs14:105425455-105425455;hs20:28212606-28212606,hs3:84522975-84522975;hs3:80977085-80977085,hs1:158052243-158052243 Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention. NCBI 36/hg18 phs000532 Yes NA CTDB0014 Research 23699601 Ryan D. Morin, Karen Mungall, Erin Pleasance, Andrew J. Mungall, Rodrigo Goya, Ryan D. Huff, David W. Scott, Jiarui Ding, Andrew Roth, Readman Chiu, Richard D. Corbett, Fong Chun Chan, Maria Mendez-Lago, Diane L. Trinh, Madison Bolger-Munro, Greg Taylor, Alireza Hadj Khodabakhshi, Susana Ben-Neriah, Julia Pon, Barbara Meissner, Bruce Woolcock, Noushin Farnoud, Sanja Rogic, Emilia L. Lim, Nathalie A. Johnson, Sohrab Shah, Steven Jones, Christian Steidl, Robert Holt, Inanc Birol, Richard Moore, Joseph M. Connors, Randy D. Gascoyne, Marco A. Marra Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing Blood 2013 Aug 6,8,12,15 Diffuse large B-cell lymphoma Next Generation Sequencing Homo sapiens RG065 Illumina HiSeq 2000 chr11:71343029-73802765:-1;chr12:68010736-68052393:1;chr13:49224823-50468703:-1;chr5:72192415-72193673:-1;chr6:105567621-132861645:-1;chr6:139952895-147336937:1;chr6:3009669-139952687:1 hs1:98275905-98275905,hs1:113273697-113273697;hs12:14506772-14506772,hs7:149989270-149989270;hs12:14514646-14514646,hs15:53207573-53207573;hs12:16829260-16829260,hs15:54045543-54045543;hs12:29522767-29522767,hs12:32709099-32709099;hs12:47646759-47646759,hs6:149700841-149700841;hs12:79781431-79781431,hs15:82417226-82417226;hs12:119440408-119440408,hs6:142993440-142993440;hs15:40231347-40231347,hs12:80162742-80162742;hs15:100006694-100006694,hs7:121288645-121288645;hs19:11504357-11504357,hs22:16500825-16500825;hs3:31670104-31670104,hs5:78448167-78448167;hs4:49021102-49021102,hs1:141547959-141547959;hs6:110462792-110462792,hs6:149748688-149748688;hs6:132761733-132761733,hs6:139232864-139232864;hs8:11037250-11037250,hs7:16958961-16958961;hs8:11613426-11613426,hs8:15450879-15450879;hs8:11631937-11631937,hs12:80817101-80817101;hs8:12284062-12284062,hs15:53985158-53985158;hs8:15450613-15450613,hs12:80256871-80256871;hs8:15554496-15554496,hs12:68010980-68010980;hs8:27950108-27950108,hs1:204062668-204062668 Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention. NCBI 36/hg18 phs000532 Yes NA CTDB0015 Research 23699601 Ryan D. Morin, Karen Mungall, Erin Pleasance, Andrew J. Mungall, Rodrigo Goya, Ryan D. Huff, David W. Scott, Jiarui Ding, Andrew Roth, Readman Chiu, Richard D. Corbett, Fong Chun Chan, Maria Mendez-Lago, Diane L. Trinh, Madison Bolger-Munro, Greg Taylor, Alireza Hadj Khodabakhshi, Susana Ben-Neriah, Julia Pon, Barbara Meissner, Bruce Woolcock, Noushin Farnoud, Sanja Rogic, Emilia L. Lim, Nathalie A. Johnson, Sohrab Shah, Steven Jones, Christian Steidl, Robert Holt, Inanc Birol, Richard Moore, Joseph M. Connors, Randy D. Gascoyne, Marco A. Marra Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing Blood 2013 Aug 1,7 Diffuse large B-cell lymphoma Next Generation Sequencing Homo sapiens RG074 Illumina HiSeq 2000 chr1:161136806-164717238:-1;chr1:165516699-166573985:-1;chr1:165525571-166580798:1;chr1:169353666-169846970:1;chr1:169966121-171343966:-1;chr2:85107885-85109419:-1;chr7:105070585-106658688:-1;chr7:110440087-110968574:-1;chr7:85466212-104951519:1;chr7:87605427-106955682:-1;chr9:13774490-125208378:-1;chr9:22774444-125209873:1;chrX:151065582-151261917:-1 hs7:112055184-112055184,hs7:112094401-112094401;hs1:165837846-165837846,hs1:169870169-169870169;hs7:105066896-105066896,hs7:106645924-106645924;hs7:111796478-111796478,hs7:111806087-111806087;hs7:111916426-111916426,hs7:112093752-112093752;hs1:168679194-168679194,hs1:168895539-168895539;hs1:13101833-13101833,hs7:109944707-109944707;hsY:11929072-11929072,hs10:41706096-41706096;hs7:82539845-82539845,hs13:99069416-99069416;hs7:109852760-109852760,hs7:109873275-109873275;hs7:89334567-89334567,hs7:106168598-106168598;hs7:97968349-97968349,hs7:110474110-110474110;hs2:88942551-88942551,hs2:88978418-88978418;hs20:28252248-28252248,hs7:105752285-105752285;hs1:159430181-159430181,hs1:172193289-172193289;hs9:44010661-44010661,hs2:94838950-94838950;hs1:163359478-163359478,hs1:163382721-163382721;hs17:827988-827988,hs3:80842380-80842380;hs3:57430662-57430662,hs3:60881705-60881705 Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention. NCBI 36/hg18 phs000532 Yes NA CTDB0016 Research 23699601 Ryan D. Morin, Karen Mungall, Erin Pleasance, Andrew J. Mungall, Rodrigo Goya, Ryan D. Huff, David W. Scott, Jiarui Ding, Andrew Roth, Readman Chiu, Richard D. Corbett, Fong Chun Chan, Maria Mendez-Lago, Diane L. Trinh, Madison Bolger-Munro, Greg Taylor, Alireza Hadj Khodabakhshi, Susana Ben-Neriah, Julia Pon, Barbara Meissner, Bruce Woolcock, Noushin Farnoud, Sanja Rogic, Emilia L. Lim, Nathalie A. Johnson, Sohrab Shah, Steven Jones, Christian Steidl, Robert Holt, Inanc Birol, Richard Moore, Joseph M. Connors, Randy D. Gascoyne, Marco A. Marra Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing Blood 2013 Aug 1,4,11,12 Diffuse large B-cell lymphoma Next Generation Sequencing Homo sapiens RG081 Illumina HiSeq 2000 chr10:135210223-135221652:-1;chr11:48324097-48330277:-1;chr11:77458412-77470894:-1;chr12:62518696-62526039:-1;chr15:42783127-42792027:-1;chr19:1839676-56743095:-1;chr19:57953041-61224839:-1;chr2:15290346-15403819:-1;chr2:228700177-228775363:-1;chr2:60515103-60536057:1;chr3:103031169-103221628:1;chr3:120755640-120766403:-1;chr5:77661760-77791264:-1;chr6:78415700-159397414:-1;chr7:31109735-31122428:1;chr8:59981864-60072798:-1;chr9:104534247-104552540:1 hs1:169413686-169413686,hs1:169451283-169451283;hs11:58248849-58248849,hs11:58291772-58291772;hs12:14067180-14067180,hs12:14086713-14086713;hs12:14076874-14076874,hs2:222123802-222123802;hs12:93617229-93617229,hs12:93641630-93641630;hs12:93624809-93624809,hs12:93640657-93640657;hs4:38520630-38520630,hs4:38536299-38536299;hs4:65363665-65363665,hs4:65373125-65373125;hs4:65364279-65364279,hs4:65411541-65411541 Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention. NCBI 36/hg18 phs000532 Yes NA CTDB0017 Research 23699601 Ryan D. Morin, Karen Mungall, Erin Pleasance, Andrew J. Mungall, Rodrigo Goya, Ryan D. Huff, David W. Scott, Jiarui Ding, Andrew Roth, Readman Chiu, Richard D. Corbett, Fong Chun Chan, Maria Mendez-Lago, Diane L. Trinh, Madison Bolger-Munro, Greg Taylor, Alireza Hadj Khodabakhshi, Susana Ben-Neriah, Julia Pon, Barbara Meissner, Bruce Woolcock, Noushin Farnoud, Sanja Rogic, Emilia L. Lim, Nathalie A. Johnson, Sohrab Shah, Steven Jones, Christian Steidl, Robert Holt, Inanc Birol, Richard Moore, Joseph M. Connors, Randy D. Gascoyne, Marco A. Marra Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing Blood 2013 Aug 2,8 Diffuse large B-cell lymphoma Next Generation Sequencing Homo sapiens RG116 Illumina HiSeq 2000 chr10:37310572-59129250:-1;chr11:48324097-48330277:-1;chr12:126618424-126647066:1;chr13:18813546-53873925:-1;chr18:20509151-46914186:-1;chr1:237482552-237691235:1;chr1:3327087-8593408:-1;chr2:40798455-50552509:1;chr2:51424401-51528988:1;chr2:51425299-53158169:-1;chr3:1807114-3815014:1;chr6:109617475-110600692:1;chr6:109684178-109707834:1;chr6:109749781-109925749:1;chr6:136951284-139215017:-1;chr9:104573081-129090329:1;chrX:7327904-37082985:-1 hs10:109651099-109651099,hs10:109682554-109682554;hs10:127180408-127180408,hs10:127191092-127191092;hs14:86394108-86394108,hs14:99079370-99079370;hs14:105397889-105397889,hs3:189143698-189143698;hs14:105397897-105397897,hs3:189143731-189143731;hs2:53751682-53751682,hs7:158463320-158463320;hs22:15293067-15293067,hs6:165001564-165001564;hs3:2928142-2928142,hs3:5234158-5234158;hs3:3820714-3820714,hs3:5631812-5631812;hs3:5653917-5653917,hs3:5741494-5741494;hs3:23819256-23819256,hs3:23831402-23831402;hs3:26226052-26226052,hs3:28419205-28419205;hs3:27553307-27553307,hs2:34024816-34024816;hs3:156749177-156749177,hs3:192809310-192809310;hs3:178046832-178046832,hs3:192809461-192809461;hs5:2255807-2255807,hs20:51824061-51824061;hs6:108388775-108388775,hs6:110631606-110631606;hs6:109707669-109707669,hs6:109714992-109714992;hs6:109740948-109740948,hs6:109764520-109764520;hs6:109908135-109908135,hs4:150073818-150073818;hs6:109912609-109912609,hs6:109928181-109928181;hs6:112095624-112095624,hs6:114557104-114557104;hs8:4485226-4485226,hsX:57953555-57953555;hs8:19772839-19772839,hs8:137370851-137370851;hs9:5725249-5725249,hs8:121983547-121983547; Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention. NCBI 36/hg18 phs000532 Yes NA CTDB0018 Research 23699601 Ryan D. Morin, Karen Mungall, Erin Pleasance, Andrew J. Mungall, Rodrigo Goya, Ryan D. Huff, David W. Scott, Jiarui Ding, Andrew Roth, Readman Chiu, Richard D. Corbett, Fong Chun Chan, Maria Mendez-Lago, Diane L. Trinh, Madison Bolger-Munro, Greg Taylor, Alireza Hadj Khodabakhshi, Susana Ben-Neriah, Julia Pon, Barbara Meissner, Bruce Woolcock, Noushin Farnoud, Sanja Rogic, Emilia L. Lim, Nathalie A. Johnson, Sohrab Shah, Steven Jones, Christian Steidl, Robert Holt, Inanc Birol, Richard Moore, Joseph M. Connors, Randy D. Gascoyne, Marco A. Marra Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing Blood 2013 Aug 16,17,2,6,8,X Diffuse large B-cell lymphoma Next Generation Sequencing Homo sapiens RG132 Illumina HiSeq 2000 chr16:28538120-29886949:-1;chr2:53036933-79163725:-1;chr2:59927998-114919109:1;chr2:66623177-84383564:-1;chr2:67023548-106133091:1;chr2:78392100-103293338:1;chr8:36998729-80575343:-1;chrX:33795147-34222789:1 hs17:21056252-21056252,hs17:21069872-21069872;hs17:21134312-21134312,hs10:41936522-41936522;hs2:50528422-50528422,hs2:103156366-103156366;hs2:67565481-67565481,hs2:94743186-94743186;hs2:99497033-99497033,hs2:106139452-106139452;hs6:58886185-58886185,hs13:106609271-106609271;hs8:2792863-2792863,hs8:43026187-43026187;hs8:29602247-29602247,hs8:30277494-30277494;hs8:36974639-36974639,hs8:36999408-36999408;hs8:40756189-40756189,hs8:56172812-56172812 Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention. NCBI 36/hg18 phs000532 Yes NA CTDB0019 Research 23699601 Ryan D. Morin, Karen Mungall, Erin Pleasance, Andrew J. Mungall, Rodrigo Goya, Ryan D. Huff, David W. Scott, Jiarui Ding, Andrew Roth, Readman Chiu, Richard D. Corbett, Fong Chun Chan, Maria Mendez-Lago, Diane L. Trinh, Madison Bolger-Munro, Greg Taylor, Alireza Hadj Khodabakhshi, Susana Ben-Neriah, Julia Pon, Barbara Meissner, Bruce Woolcock, Noushin Farnoud, Sanja Rogic, Emilia L. Lim, Nathalie A. Johnson, Sohrab Shah, Steven Jones, Christian Steidl, Robert Holt, Inanc Birol, Richard Moore, Joseph M. Connors, Randy D. Gascoyne, Marco A. Marra Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing Blood 2013 Aug 8,11,18 Diffuse large B-cell lymphoma Next Generation Sequencing Homo sapiens RG138 Illumina HiSeq 2000 chr11:18716208-45329936:1;chr1:115502658-121186800:-1;chr1:6182243-95195626:-1;chr8:128525264-129544861:1;chr8:129282247-131956016:-1;chr8:50109248-70530204:1;chrX:152759760-153024102:1 hs8:50172131-50172131,hs8:70391059-70391059;hs2:4183144-4183144,hs2:4201354-4201354;hs6:58886798-58886798,hs6:75169496-75169496;hs11:45359344-45359344,hs11:46160005-46160005;hs17:21134312-21134312,hs10:41936522-41936522;hs3:183427260-183427260,hs3:183529139-183529139;hs4:105162145-105162145,hs4:106553660-106553660;hs4:105162153-105162153,hs4:105226236-105226236;hs19:1871143-1871143,hs19:2463361-2463361;hs6:58887071-58887071,hs6:76237245-76237245;hs18:35880144-35880144,hs18:55105867-55105867;hs22:15399058-15399058,hs12:120804324-120804324;hs8:37903757-37903757,hs4:190921474-190921474;hs8:50080227-50080227,hs8:70531495-70531495;hs18:35881611-35881611,hs18:52677321-52677321;hs18:36402620-36402620,hs18:54945798-54945798;hs18:36678172-36678172,hs18:52829615-52829615 Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention. NCBI 36/hg18 phs000532 Yes NA CTDB0021 Research 23615946 Teles Alves I, Hiltemann S, Hartjes T, van der Spek P, Stubbs A, Trapman J, Jenster G Gene fusions by chromothripsis of chromosome 5q in the VCaP prostate cancer cell line Hum Genet 2013 Apr 5 Prostate cancer Next Generation Sequencing Homo sapiens 23615946_1 chr10:100015126-100015461:-1;chr10:10533425-10533748:-1;chr10:10707181-10707395:1;chr10:1074760-1075201:-1;chr10:107940674-107941587:-1;chr10:107985984-107987724:-1;chr10:108020311-108022535:-1;chr10:109628475-109629682:-1;chr10:111562112-111568218:-1;chr10:112007470-112008975:-1;chr10:114102173-114106650:-1;chr10:114148103-114148443:-1;chr10:119624273-119624604:-1;chr10:11985439-11985778:-1;chr10:122216763-122218911:-1;chr10:12329100-12329538:-1;chr10:12600468-12602982:-1;chr10:127503325-127503744:1;chr10:127735177-127735977:-1;chr10:132748479-132748828:-1;chr10:134015591-134016188:-1;chr10:134954781-134955956:-1;chr10:18543082-18543596:-1;chr10:18585230-18585713:1;chr10:19437323-19437661:-1;chr10:25138095-25138433:-1;chr10:27039082-27042219:-1;chr10:27264209-27268094:-1;chr10:28690422-28691065:-1;chr10:29752157-29752732:-1;chr10:31286753-31291775:-1;chr10:32297889-32300621:-1;chr10:3443365-3443565:1;chr10:35633228-35633558:-1;chr10:42594217-42594549:-1;chr10:4280063-4281683:-1;chr10:4698518-4700522:-1;chr10:47112729-47113167:-1;chr10:49587177-49587500:-1;chr10:49948021-49948338:-1;chr10:5192142-5314899:1;chr10:5192144-5314801:1;chr10:54111215-54111532:-1;chr10:54453548-54458835:-1;chr10:5627102-5677118:-1;chr10:56352786-56354366:-1;chr10:57372053-57372393:-1;chr10:58533556-58533875:-1;chr10:58685232-58685574:-1;chr10:5929614-5932869:-1;chr10:6451572-6457638:-1;chr10:66702392-66702807:-1;chr10:67098629-67098743:1;chr10:70456367-70457350:-1;chr10:77925584-77931031:-1;chr10:78470917-78471236:-1;chr10:80762188-80762786:-1;chr10:82727731-82728050:-1;chr10:829811-830244:-1;chr10:84117799-84120349:-1;chr10:84227969-84228462:-1;chr10:86791754-86792420:1;chr10:86791756-86792583:1;chr10:89265777-89266548:-1;chr10:92959211-92959549:-1;chr10:94124579-94127633:-1;chr10:9465102-9465785:-1;chr10:95535467-95536485:-1;chr10:9559834-9560140:-1;chr10:97196775-97198010:1;chr10:97197045-97198018:1;chr10:99024858-99027392:-1;chr11:100921994-100922324:-1;chr11:102916041-102916354:-1;chr11:103772960-103778441:-1;chr11:104260369-104267776:-1;chr11:104900268-104900463:1;chr11:105228702-105229033:-1;chr11:1068851-1069538:-1;chr11:1082392-1082743:1;chr11:112122958-112123362:-1;chr11:113930121-113937141:-1;chr11:113938523-130735676:-1;chr11:1169421-1170150:1;chr11:117797880-117799063:1;chr11:11876611-11877293:-1;chr11:121852806-121854510:-1;chr11:123615342-123626451:1;chr11:124558309-124558599:-1;chr11:12475067-12479764:-1;chr11:128187926-128188620:-1;chr11:131429477-131435514:1;chr11:132729329-132729463:1;chr11:13522498-13522866:-1;chr11:1611076-1613399:-1;chr11:1619610-1620141:-1;chr11:24306071-24312137:-1;chr11:25521062-25521403:-1;chr11:27264456-27264789:-1;chr11:28963778-28969464:-1;chr11:29096068-29097017:-1;chr11:29924155-29925043:-1;chr11:31350352-31354225:-1;chr11:33494263-33494586:-1;chr11:380643-380983:-1;chr11:43848415-43848751:-1;chr11:45386425-45388192:-1;chr11:47014164-47020282:-1;chr11:48308216-48308717:-1;chr11:48324094-48330275:-1;chr11:48557434-48560860:-1;chr11:5716663-5718941:-1;chr11:57923564-57924732:-1;chr11:58350764-58352595:-1;chr11:60327998-60328477:-1;chr11:61975027-61975559:-1;chr11:632713-632853:1;chr11:63455482-63458520:1;chr11:63455485-63458230:1;chr11:65398687-65400099:-1;chr11:66468335-66470146:-1;chr11:667346-667800:-1;chr11:67788432-67788708:1;chr11:68488046-68488178:1;chr11:69110024-69110586:-1;chr11:69895078-69895324:1;chr11:70479247-70479338:1;chr11:7469350-7469572:1;chr11:81178153-81198987:-1;chr11:81233831-81234198:-1;chr11:85963609-85964370:-1;chr11:92660787-92661808:-1;chr11:93318883-93321077:-1;chr11:94809028-94815080:-1;chr11:970110-970572:-1;chr11:97753418-97753812:-1;chr11:98781548-98781888:-1;chr12:102817537-102817865:-1;chr12:105301795-105302326:-1;chr12:10594768-10595095:-1;chr12:107790203-107790779:-1;chr12:113476014-114587554:-1;chr12:114561828-114564280:1;chr12:114561908-114564288:1;chr12:120967520-120969661:-1;chr12:121576304-121576633:-1;chr12:12579561-12774925:-1;chr12:127758884-127759297:1;chr12:128406650-128406963:-1;chr12:128626256-128626587:-1;chr12:129697891-129699822:-1;chr12:13055636-13056119:1;chr12:1308253-1308873:-1;chr12:131452436-131452790:-1;chr12:131559648-131560865:-1;chr12:15909933-15912926:-1;chr12:17336094-17337206:-1;chr12:1734128-1734587:-1;chr12:17498621-17499125:-1;chr12:19094792-19096942:-1;chr12:24832191-24832893:-1;chr12:26402304-26402636:-1;chr12:27325270-27325601:-1;chr12:30262584-30263009:-1;chr12:30369554-30372260:-1;chr12:30809559-30810059:-1;chr12:32854882-32855197:-1;chr12:39946098-39946415:-1;chr12:40524325-40525149:-1;chr12:41940696-41941032:-1;chr12:42263720-42265820:-1;chr12:44189420-44196206:-1;chr12:45361633-45361981:-1;chr12:47011739-47014653:-1;chr12:47196861-47197511:-1;chr12:48468879-48469137:1;chr12:48468921-48469096:1;chr12:4952523-4953425:-1;chr12:52531689-52531978:-1;chr12:54013481-54014455:-1;chr12:56314315-56315538:-1;chr12:570211-570521:-1;chr12:58808109-58811305:-1;chr12:60703428-60706497:-1;chr12:6408426-6408956:-1;chr12:64813918-64816159:-1;chr12:67542046-67542788:-1;chr12:68881131-68883862:-1;chr12:69819060-69820021:1;chr12:69819544-69820019:1;chr12:70475426-70476841:-1;chr12:70642936-70644500:-1;chr12:76908009-76912402:1;chr12:76908021-76911976:1;chr12:7714131-7715808:-1;chr12:78678919-78686802:1;chr12:82368189-82368753:-1;chr12:82483361-82483677:-1;chr12:83117245-83120148:-1;chr12:85728921-85729824:1;chr12:85728949-85729962:1;chr12:86664575-86668037:-1;chr12:8908352-8909378:-1;chr12:899181-899990:-1;chr12:93768157-93768580:-1;chr12:94757723-94760469:-1;chr12:94864479-94867088:-1;chr12:96078872-96079200:-1;chr13:100692147-100694428:-1;chr13:101588745-101589037:-1;chr13:102889766-102890248:-1;chr13:109215825-109217148:-1;chr13:109763907-109764213:-1;chr13:110127712-110128130:-1;chr13:110357429-110357667:-1;chr13:110378891-110379079:1;chr13:110388551-110388744:1;chr13:110502484-110502967:-1;chr13:112547565-112548162:-1;chr13:24543201-24543520:-1;chr13:25948044-25950189:-1;chr13:26444935-26445685:1;chr13:28789572-28789883:-1;chr13:28852771-28853095:-1;chr13:33709550-33713591:1;chr13:36969943-36983580:-1;chr13:37955317-37958203:-1;chr13:38832272-38833569:-1;chr13:41845268-41845652:1;chr13:42437804-42439457:-1;chr13:44903455-44903792:-1;chr13:48431462-48434622:-1;chr13:48849402-48851862:-1;chr13:49967351-49973083:-1;chr13:54839183-54839473:-1;chr13:59070499-59070832:-1;chr13:59414657-59419060:-1;chr13:62503292-62503649:1;chr13:64250195-64251683:-1;chr13:64535809-64536211:-1;chr13:66072780-66075422:-1;chr13:66961941-68911122:-1;chr13:68924879-73518819:-1;chr13:71375266-71378578:-1;chr13:72972922-72973250:-1;chr13:73813282-73814999:1;chr13:76261224-76261400:1;chr13:80179270-80179509:1;chr13:80645256-80645584:-1;chr13:81787213-81787556:-1;chr13:82063937-82070208:-1;chr13:84834702-84835633:-1;chr13:89660856-89662811:-1;chr13:95431437-95431755:-1;chr13:97302994-97303304:1;chr13:97519242-97519562:-1;chr13:98033865-98038384:-1;chr14:100062873-100063032:1;chr14:101060629-101060965:-1;chr14:103432670-103432868:1;chr14:104345035-104345834:-1;chr14:104486465-104488940:-1;chr14:104699860-104700105:1;chr14:104809322-104809682:-1;chr14:105120093-105120364:1;chr14:106003685-106245975:-1;chr14:106232718-106232836:1;chr14:21022336-21024502:-1;chr14:21951507-21952100:-1;chr14:22992091-22992491:-1;chr14:23244869-23245201:-1;chr14:23439250-23439455:1;chr14:25216955-25217312:-1;chr14:27939597-27941914:-1;chr14:28797794-28798558:-1;chr14:32461723-32462059:-1;chr14:33583777-33584587:-1;chr14:39168144-39169966:-1;chr14:39679566-39687423:-1;chr14:40445654-40446509:1;chr14:40445785-40446500:1;chr14:41556085-41556400:-1;chr14:45647688-45648008:-1;chr14:46777323-46787597:-1;chr14:47393717-47395012:1;chr14:47393718-47395230:1;chr14:49261790-49262106:1;chr14:53633816-53634150:-1;chr14:54820981-54821839:-1;chr14:56100977-56101330:-1;chr14:58953231-58953831:-1;chr14:60127808-60129242:-1;chr14:64676246-64677938:-1;chr14:65328048-65328163:1;chr14:67672811-67673511:-1;chr14:69086749-69092243:-1;chr14:70507589-70507922:-1;chr14:72621755-72678268:1;chr14:72621992-72678176:1;chr14:77897998-77898349:-1;chr14:79176043-79184804:-1;chr14:80538880-80539192:-1;chr14:80947964-80950365:-1;chr14:81568863-81573083:-1;chr14:82705606-82706253:-1;chr14:84366861-84371908:-1;chr14:85527474-85559338:-1;chr14:86927817-86928144:-1;chr14:96244925-96245553:-1;chr14:97844293-97844622:-1;chr14:99914767-99915100:-1;chr15:18805551-18807444:1;chr15:19838217-19845457:-1;chr15:22077030-22078838:-1;chr15:22390426-22390748:-1;chr15:22668233-22669975:-1;chr15:24572589-24572897:-1;chr15:27198774-27199196:-1;chr15:32796325-32796660:-1;chr15:37054308-37054662:-1;chr15:37159828-37160937:-1;chr15:37531683-37532152:-1;chr15:41447733-41448059:-1;chr15:47332155-47335146:-1;chr15:48708647-48709089:-1;chr15:53005515-53011724:-1;chr15:60493387-60495087:-1;chr15:60972730-60972823:1;chr15:62420246-62420571:-1;chr15:62630842-62631268:-1;chr15:64664849-64665470:-1;chr15:65321533-65321867:-1;chr15:66213058-66215983:-1;chr15:66770736-66771032:-1;chr15:68808907-68814576:-1;chr15:69495663-69500744:-1;chr15:69668623-69670020:-1;chr15:69804361-69804721:-1;chr15:70173114-70175307:-1;chr15:75778718-75779124:1;chr15:77592038-77592397:-1;chr15:78991504-78992928:1;chr15:80352932-80354856:-1;chr15:83858260-83860085:-1;chr15:85500991-85501455:-1;chr15:90475579-90478076:-1;chr15:93646146-94779750:1;chr15:93646374-94779979:1;chr15:96634540-96634949:-1;chr15:96659847-96661330:-1;chr15:96717594-96718160:-1;chr15:97474127-97474924:-1;chr15:98234187-98240761:-1;chr15:98869339-98869841:-1;chr15:98902070-98902226:1;chr15:99270604-99270913:-1;chr15:99479729-99479834:1;chr16:11511245-11512526:-1;chr16:1362929-1364192:-1;chr16:13681632-13681971:1;chr16:16841867-16847918:-1;chr16:18740031-18745883:-1;chr16:19137937-19138289:-1;chr16:20686058-20686378:-1;chr16:22955276-22957032:-1;chr16:23363166-23363466:-1;chr16:23436048-23436361:-1;chr16:23818388-23818694:-1;chr16:25247612-25250630:-1;chr16:25546880-25547654:-1;chr16:26292872-26293745:1;chr16:26515538-26515880:-1;chr16:33281678-33286906:-1;chr16:46838423-46838876:1;chr16:47066631-47069092:-1;chr16:50969872-50972344:-1;chr16:53217871-53218180:-1;chr16:55883899-55885661:-1;chr16:57231393-57234894:-1;chr16:58589594-58589908:-1;chr16:68412186-68416522:1;chr16:69110525-69110845:-1;chr16:69535300-69537395:-1;chr16:736322-736763:-1;chr16:73987388-73988230:-1;chr16:75096634-75101526:-1;chr16:75648141-75650363:-1;chr16:76929139-76942399:-1;chr16:79676975-79677328:-1;chr16:83746170-83747348:1;chr16:83746443-83747111:1;chr16:84841822-84842130:-1;chr16:8663018-8664583:-1;chr17:11352392-11353039:-1;chr17:122941-123417:-1;chr17:136843-138717:-1;chr17:14130636-14132281:-1;chr17:1642868-1643330:-1;chr17:17171232-17171971:-1;chr17:18731870-18732895:-1;chr17:1902473-1903103:-1;chr17:193767-197057:-1;chr17:19512502-19512912:-1;chr17:20646-21786:-1;chr17:21261870-21263414:-1;chr17:21268597-22333549:-1;chr17:22560670-22564512:-1;chr17:23804514-23807620:-1;chr17:24836656-24839587:1;chr17:29897094-29898731:-1;chr17:35631636-35632107:-1;chr17:36785493-36792803:1;chr17:37743524-37744124:-1;chr17:38793635-38795854:-1;chr17:38872593-38873881:-1;chr17:39046338-39055505:1;chr17:41643642-42531128:1;chr17:44392201-44392841:-1;chr17:44583441-44583771:-1;chr17:44706940-44708108:-1;chr17:45782519-45782903:-1;chr17:495871-496891:-1;chr17:53042810-53044915:-1;chr17:60926566-60926978:1;chr17:65469279-65469678:1;chr17:67363749-67364076:-1;chr17:685804-686161:-1;chr17:69234162-69234622:-1;chr17:71873832-71876903:-1;chr17:72499125-72499444:-1;chr17:73499893-73500208:-1;chr17:73793858-73795052:-1;chr17:748509-748978:-1;chr17:76189947-76190874:-1;chr17:76332074-76333401:-1;chr17:76742916-76743255:-1;chr17:78653184-78654274:-1;chr18:13133169-13134161:-1;chr18:21146492-21146816:-1;chr18:24081890-24082223:-1;chr18:25883688-25884014:-1;chr18:33172064-33172379:-1;chr18:33560058-33560630:-1;chr18:33569634-33569952:-1;chr18:39285550-39286534:-1;chr18:44250160-44250477:-1;chr18:45273866-45274188:-1;chr18:48716565-48717030:-1;chr18:49179990-49180313:-1;chr18:49690052-49690417:-1;chr18:50206966-50210962:-1;chr18:52644285-52644504:1;chr18:53097735-53099715:-1;chr18:5314645-5316244:-1;chr18:53822134-53822440:-1;chr18:59036817-59037037:1;chr18:65143796-65145076:-1;chr18:69424394-69424715:-1;chr18:72476189-72476985:-1;chr18:72494452-72494770:-1;chr18:73395986-73397148:-1;chr18:74303112-74304331:-1;chr18:74474625-74475465:-1;chr18:75061700-75061765:1;chr18:75410938-75413079:-1;chr18:75600869-75601199:-1;chr18:75641237-75641552:-1;chr19:1093016-1093275:1;chr19:1133661-1134223:-1;chr19:11615682-11718097:1;chr19:13598523-13599759:1;chr19:14527925-18884406:1;chr19:14907392-14910478:-1;chr19:17122381-17122818:-1;chr19:22932641-22934759:-1;chr19:23112643-23112960:-1;chr19:23727768-23728232:1;chr19:2856002-11330155:-1;chr19:34642025-34648008:-1;chr19:35080645-35084955:-1;chr19:35979345-35981618:-1;chr19:41738035-41738351:-1;chr19:45304944-45307615:-1;chr19:45845112-45847858:-1;chr19:48875206-48875794:1;chr19:495690-496093:1;chr19:50970509-50971483:-1;chr19:51647947-51648274:-1;chr19:517406-520612:-1;chr19:53064591-53066079:-1;chr19:5460876-5461844:-1;chr19:56098661-56100237:-1;chr19:57061794-57270693:1;chr19:58308291-58308609:-1;chr19:58380998-58383780:-1;chr19:59429099-59429561:-1;chr19:60296561-60297505:-1;chr19:60733654-60733990:-1;chr19:61283163-61283853:-1;chr19:61872732-61873332:-1;chr19:63309600-63309940:-1;chr19:6730205-6732062:-1;chr19:8420425-8420732:-1;chr19:8626601-8626927:1;chr1:102820271-102820601:-1;chr1:102868666-102868985:-1;chr1:105817337-105824920:-1;chr1:108534847-108538774:-1;chr1:109374755-109376704:-1;chr1:109988722-109992954:-1;chr1:113601154-113601616:-1;chr1:113841365-113847415:-1;chr1:114447477-114455894:1;chr1:114447553-114455872:1;chr1:143605644-143606642:-1;chr1:143804305-143808440:-1;chr1:148958075-148958409:-1;chr1:149010434-149012164:-1;chr1:151482388-151483170:-1;chr1:152797531-153057274:-1;chr1:154793335-154795566:-1;chr1:157134157-157136608:-1;chr1:157915332-157916282:-1;chr1:16024527-16028026:-1;chr1:160319304-160319624:-1;chr1:160497372-160497915:-1;chr1:167270985-167271856:-1;chr1:167426661-167426990:-1;chr1:17548891-17550028:-1;chr1:175654988-175655191:1;chr1:176761909-176762262:-1;chr1:178450457-178450776:-1;chr1:183081360-183087416:-1;chr1:183203676-183203998:-1;chr1:185982729-185989157:-1;chr1:186806079-186806854:-1;chr1:191619687-191847016:-1;chr1:195767136-195769899:-1;chr1:197705354-197706861:-1;chr1:201951058-201952981:-1;chr1:20369780-20370328:-1;chr1:205608641-205612242:-1;chr1:20804726-20805401:-1;chr1:208893848-208894171:1;chr1:209609709-209631297:-1;chr1:210537762-210539243:-1;chr1:212836726-212837062:-1;chr1:216249125-216255231:-1;chr1:216312261-216313122:-1;chr1:217989940-217990258:-1;chr1:218569568-218570207:-1;chr1:220100781-220101113:-1;chr1:222313740-222314216:-1;chr1:224069589-224069759:-1;chr1:225212051-226730000:-1;chr1:225668697-225668901:1;chr1:226428471-226428839:-1;chr1:232653834-232654144:-1;chr1:234615724-234617967:-1;chr1:234661562-234661887:-1;chr1:236918945-236919888:-1;chr1:238707870-238708272:-1;chr1:239216496-239216821:-1;chr1:241849368-241850378:-1;chr1:24275869-24276178:-1;chr1:245917091-245923144:-1;chr1:246118115-246124275:-1;chr1:246222220-246269236:1;chr1:25031281-25034103:-1;chr1:2556114-2556490:-1;chr1:28423959-28426667:-1;chr1:3408414-3408528:1;chr1:43831945-43832549:1;chr1:4899338-4899637:1;chr1:54864862-54868555:-1;chr1:56173881-56174202:-1;chr1:56603700-56607555:-1;chr1:56768620-56768934:1;chr1:57015213-57015552:-1;chr1:58516499-58517412:-1;chr1:60833082-60835248:1;chr1:60833083-60834698:1;chr1:61060683-61060923:1;chr1:62163190-62163539:-1;chr1:62924423-62924762:-1;chr1:6360760-6368486:-1;chr1:65682226-65682496:-1;chr1:67780610-67781467:-1;chr1:72538912-72584428:-1;chr1:73526195-73526510:-1;chr1:75784458-75784788:-1;chr1:77248983-77249313:1;chr1:80966941-80967268:-1;chr1:81177350-81183541:-1;chr1:81195122-81197022:-1;chr1:81432939-81434143:1;chr1:81432944-81433958:1;chr1:81460382-81460711:-1;chr1:82735892-82736421:-1;chr1:82898554-82900165:-1;chr1:84290527-84297231:-1;chr1:84484602-84488462:-1;chr1:859347-860187:-1;chr1:86513574-86514291:-1;chr1:89371420-89424493:1;chr1:89371762-89424837:1;chr1:91334109-93287270:-1;chr1:91397375-91397658:-1;chr1:91686699-91687154:-1;chr1:9393770-9393942:1;chr1:94060963-94063847:-1;chr20:21234117-21236799:-1;chr20:2164983-2165103:1;chr20:2307701-2308614:1;chr20:2307903-2308608:1;chr20:24458425-24458672:1;chr20:25531216-25531680:-1;chr20:2751153-2754415:-1;chr20:2969829-2970123:-1;chr20:30362900-30363205:-1;chr20:30791087-30791759:-1;chr20:315482-327903:-1;chr20:32279596-32282893:-1;chr20:32705520-32707945:-1;chr20:33085327-33085649:-1;chr20:36715101-36715400:1;chr20:39339909-39341095:-1;chr20:41458018-41459216:-1;chr20:41758529-41759033:1;chr20:42109542-42109941:-1;chr20:43968884-43969320:-1;chr20:44933562-44936343:-1;chr20:47375581-47375665:1;chr20:51886466-51886931:-1;chr20:53868019-53874025:-1;chr20:53896641-53896958:-1;chr20:5577259-5578598:-1;chr20:56703469-56703812:1;chr20:59337734-59337925:1;chr20:59340009-59340173:1;chr20:59407575-59407896:-1;chr20:5973724-5975642:-1;chr20:60004033-60004352:-1;chr20:61195143-61196042:-1;chr20:61738061-61738572:-1;chr20:62066707-62067941:-1;chr20:62192635-62193142:-1;chr20:62233789-62235707:-1;chr21:10103742-10139222:-1;chr21:15510251-15513325:-1;chr21:17534203-17535507:-1;chr21:21705346-21706582:1;chr21:23296667-23297282:-1;chr21:29185620-29186169:-1;chr21:29474096-29474450:-1;chr21:29523696-29524036:-1;chr21:34700254-34700371:1;chr21:38403423-38403793:-1;chr21:38512412-38512758:-1;chr21:41324766-41325087:-1;chr21:42371397-42371947:-1;chr21:42576924-42577470:-1;chr21:43794795-43797731:-1;chr21:44443626-44445148:-1;chr21:45225990-45226784:-1;chr21:46212457-46214160:-1;chr21:46481780-46483102:-1;chr22:16427375-16427733:-1;chr22:17479932-17480627:-1;chr22:17951619-17953102:-1;chr22:21033195-21082531:1;chr22:21808557-21809688:-1;chr22:21906857-21907813:-1;chr22:22355618-22357539:-1;chr22:22525949-22528520:-1;chr22:25498076-25499802:-1;chr22:33975166-33976141:-1;chr22:34942947-34944266:-1;chr22:35473267-35477993:-1;chr22:39124202-39125221:-1;chr22:39470063-39472584:-1;chr22:41431558-41432317:-1;chr22:43679048-43679409:-1;chr22:44102628-44102956:-1;chr22:47023887-47024205:-1;chr22:47450166-47451027:-1;chr22:48008515-48010376:1;chr22:48008519-48010305:1;chr2:100535795-100541525:1;chr2:101341646-101341979:-1;chr2:101723047-101723362:-1;chr2:105028539-105032024:-1;chr2:106245998-106252349:-1;chr2:1079759-1080712:-1;chr2:108221850-108222713:-1;chr2:1085285-1085367:1;chr2:108877528-108877911:-1;chr2:110210043-111169574:-1;chr2:115344577-115345316:-1;chr2:117609533-117609872:-1;chr2:11911731-11912738:-1;chr2:119999252-119999614:1;chr2:120133549-120134958:1;chr2:120133670-120134968:1;chr2:124768226-124769710:1;chr2:124768229-124769384:1;chr2:126226185-126227072:-1;chr2:127391228-127393744:-1;chr2:129195608-129195973:1;chr2:1337182-1337523:-1;chr2:134176749-134177056:-1;chr2:134683175-134686605:-1;chr2:134976989-134978439:1;chr2:142041771-142045516:-1;chr2:142067473-142067798:-1;chr2:151611335-151611611:-1;chr2:152325547-152325862:-1;chr2:153504241-153507989:-1;chr2:159857365-159859896:-1;chr2:1602104-1602491:-1;chr2:161503856-161504180:-1;chr2:162040517-162042291:-1;chr2:162154729-162157604:-1;chr2:169813379-169819426:-1;chr2:176054919-176060972:-1;chr2:176973891-176980290:-1;chr2:177995883-177996307:-1;chr2:1780841-1781074:-1;chr2:182064228-182064543:-1;chr2:182565161-182565844:-1;chr2:183958226-183958569:-1;chr2:18769630-18770832:1;chr2:18769641-18771137:1;chr2:187923975-187924282:-1;chr2:18866355-18866872:-1;chr2:194397747-194407011:-1;chr2:195005383-195006692:-1;chr2:19631062-19634043:-1;chr2:202429909-202430230:-1;chr2:208059399-208067614:-1;chr2:208182730-208185032:-1;chr2:208618596-208618911:-1;chr2:216798185-216800753:-1;chr2:221054181-221054509:-1;chr2:223468427-223470920:-1;chr2:225747827-225748304:-1;chr2:226873670-226879415:-1;chr2:227949343-227966617:1;chr2:228972590-228976582:-1;chr2:229467532-229468151:-1;chr2:233786639-233787898:1;chr2:234296232-234298741:-1;chr2:240696410-240696982:-1;chr2:241374669-241374925:1;chr2:25081133-25081448:-1;chr2:32945242-32949138:-1;chr2:34549333-34590071:-1;chr2:38445595-38451115:-1;chr2:41826659-41829383:-1;chr2:42199763-42200822:-1;chr2:46763654-46763970:-1;chr2:4759185-4765250:-1;chr2:51780091-51781274:-1;chr2:54418997-54420977:-1;chr2:55918127-55919590:-1;chr2:57196247-57196574:-1;chr2:66359098-66361062:-1;chr2:69978557-69979078:-1;chr2:70514812-70515963:-1;chr2:76380011-76382406:-1;chr2:77971399-77971866:-1;chr2:82193972-82194292:-1;chr2:82889159-82889927:-1;chr2:84611964-84612257:-1;chr2:88210880-88211268:1;chr2:88810347-88813401:-1;chr2:91043624-91049215:-1;chr2:9625448-10805257:-1;chr2:98575393-233111201:1;chr2:99470145-99471463:-1;chr3:100381763-100385091:-1;chr3:100426496-100432208:-1;chr3:100520140-100520452:-1;chr3:101111472-101112321:-1;chr3:105760890-105761737:-1;chr3:113950091-113950421:-1;chr3:115751498-117385723:1;chr3:117798601-117812937:-1;chr3:118523141-119106479:1;chr3:121376675-121377135:-1;chr3:124680312-124680665:-1;chr3:124719447-124719762:-1;chr3:126372743-126373513:-1;chr3:127841628-127841955:-1;chr3:131830266-131835808:-1;chr3:133160499-133160840:-1;chr3:133471886-133477843:-1;chr3:134986460-134987776:-1;chr3:137503703-137508889:-1;chr3:141153287-141157144:1;chr3:141153403-141157144:1;chr3:141181223-141182734:-1;chr3:142027097-142029736:-1;chr3:149089353-149089930:-1;chr3:149254657-149257153:-1;chr3:149764130-149768115:-1;chr3:150049492-150049810:-1;chr3:150327076-150327404:-1;chr3:150446060-150452398:-1;chr3:150751164-150752839:-1;chr3:151360766-151361075:-1;chr3:153794419-153795851:-1;chr3:160739715-160740384:-1;chr3:161071915-161072170:1;chr3:162729422-162729757:-1;chr3:164247593-164251778:-1;chr3:168003840-168016945:1;chr3:173756977-173759294:-1;chr3:173883606-173883927:-1;chr3:178845765-178846258:-1;chr3:180032827-180033568:-1;chr3:181137035-181137500:-1;chr3:182400759-182401487:-1;chr3:185359538-185360126:-1;chr3:186500039-186500363:-1;chr3:188063727-188067996:-1;chr3:189787531-189787864:-1;chr3:192547379-192554361:-1;chr3:194227049-194227589:-1;chr3:194358026-194368102:-1;chr3:195602457-195603214:-1;chr3:195865511-195865847:-1;chr3:195880156-195881764:-1;chr3:196024583-196027549:1;chr3:196024598-196027718:1;chr3:196257534-196257615:1;chr3:203783-209416:-1;chr3:21432512-21432835:-1;chr3:22067365-22072813:-1;chr3:2286589-2286937:-1;chr3:23660752-23661215:-1;chr3:23739077-23739407:-1;chr3:25005891-25007253:-1;chr3:26425974-26427303:-1;chr3:32077056-32082889:-1;chr3:32176833-32177165:-1;chr3:32781814-32783129:-1;chr3:33117670-33122800:-1;chr3:36083138-36083456:-1;chr3:4041937-4044568:-1;chr3:41311685-41312234:-1;chr3:42813377-42815831:-1;chr3:43006100-43006428:-1;chr3:44715996-44717287:1;chr3:44716161-44717125:1;chr3:45584913-45585329:-1;chr3:49172767-49173090:-1;chr3:49258503-49260446:1;chr3:5581877-5581956:1;chr3:67576387-67579491:-1;chr3:70096166-70096579:-1;chr3:72462523-72462699:-1;chr3:75359576-75361605:-1;chr3:75869964-75870422:-1;chr3:76097246-76097427:1;chr3:77486928-77487089:1;chr3:81008004-81009297:-1;chr3:83935811-83938045:-1;chr3:8695246-8696042:-1;chr4:100242071-100242405:-1;chr4:1011542-1012213:-1;chr4:102663436-102709741:-1;chr4:103006810-103007375:-1;chr4:104004612-104004961:-1;chr4:105113495-105114129:-1;chr4:107276027-107282811:-1;chr4:108347267-108351173:-1;chr4:108767094-109449812:1;chr4:109327139-109327440:-1;chr4:110718206-110718531:-1;chr4:114205356-114205851:-1;chr4:115394577-115403287:-1;chr4:11544436-11545200:-1;chr4:115727270-115733313:-1;chr4:116148172-116151326:-1;chr4:121627110-121627433:-1;chr4:122028392-122028709:-1;chr4:134352084-134352688:-1;chr4:135652479-135655151:-1;chr4:146658263-146659907:-1;chr4:1495630-1497025:-1;chr4:152560160-152561007:-1;chr4:1572919-1573632:-1;chr4:161936572-163346664:1;chr4:164877752-164878586:-1;chr4:166222114-166224552:-1;chr4:167223766-167224369:-1;chr4:167913623-167919658:-1;chr4:170515039-170515460:-1;chr4:173225214-173229506:-1;chr4:173661607-173670095:-1;chr4:175861744-175863548:-1;chr4:176357119-176357508:-1;chr4:176669821-179435273:-1;chr4:178106326-178106642:-1;chr4:181786434-181786748:-1;chr4:182113786-182115288:-1;chr4:182293555-182294125:-1;chr4:184494983-184495571:-1;chr4:185902776-185903094:-1;chr4:18666569-18667067:-1;chr4:186678631-186681069:-1;chr4:18688553-18694653:-1;chr4:188032707-188033027:-1;chr4:189427191-189427941:-1;chr4:190030248-190030567:-1;chr4:190032436-190033123:-1;chr4:190206689-190207043:-1;chr4:190295008-190301282:-1;chr4:190342448-190343307:-1;chr4:190490847-190491169:-1;chr4:190797068-190841216:-1;chr4:190861629-190861976:-1;chr4:190893414-190894524:-1;chr4:190899926-190900721:-1;chr4:190978523-190978865:-1;chr4:191035650-191037595:-1;chr4:23330781-23331102:-1;chr4:2367642-2368296:-1;chr4:29270220-29270548:-1;chr4:31101965-31102401:-1;chr4:32184506-32184821:-1;chr4:34916650-34920831:-1;chr4:3581902-3582457:-1;chr4:3583174-3588419:-1;chr4:37008811-37009590:-1;chr4:39701447-39702813:-1;chr4:43626253-43626594:-1;chr4:44202036-44202490:-1;chr4:44204151-44204469:-1;chr4:45897554-45899785:-1;chr4:57782102-57782501:-1;chr4:57842787-57843113:-1;chr4:61012701-61015781:-1;chr4:63352021-63358721:-1;chr4:64352678-68717639:-1;chr4:64466187-64467157:-1;chr4:6702494-6703815:-1;chr4:75142130-75640405:-1;chr4:75860517-98758854:1;chr4:8046697-8047796:-1;chr4:81521563-81521902:-1;chr4:82210554-82210875:-1;chr4:83148337-83150428:-1;chr4:86879792-86880114:-1;chr4:89900496-89900818:-1;chr4:9101982-9104135:1;chr4:94778477-94784528:-1;chr4:9565932-9566250:-1;chr4:9745227-9745805:-1;chr5:101994535-158535325:1;chr5:102496345-164510566:-1;chr5:102691171-158548764:-1;chr5:102702311-165493393:-1;chr5:10326602-10328446:-1;chr5:105963955-107791485:1;chr5:10627956-10628301:-1;chr5:106352650-106354342:-1;chr5:106907856-126522875:1;chr5:10692212-10693266:-1;chr5:107208498-180411695:-1;chr5:107678936-158107975:-1;chr5:108622980-108629027:-1;chr5:1114029-1114710:-1;chr5:111472744-161919968:1;chr5:11392042-11392366:-1;chr5:113947837-159898985:-1;chr5:115158366-115158715:-1;chr5:115374616-115378962:1;chr5:115374637-115378804:1;chr5:119043047-119043367:-1;chr5:119408045-119410579:-1;chr5:12239500-12239804:-1;chr5:1231294-1233733:-1;chr5:125273398-130215224:1;chr5:127200231-127201181:-1;chr5:127435342-127438819:-1;chr5:12864019-12873525:-1;chr5:13469596-13475858:-1;chr5:136379356-153263585:-1;chr5:136882600-136884316:-1;chr5:139253406-139254458:-1;chr5:13948092-13948389:-1;chr5:142418072-169508658:-1;chr5:143468123-143468461:1;chr5:143492681-143495244:1;chr5:143493060-143495240:1;chr5:144852099-144853000:-1;chr5:150157855-150161793:-1;chr5:151436611-151442645:-1;chr5:152509159-175048229:-1;chr5:153264892-167053865:-1;chr5:155244367-155245158:-1;chr5:155378577-161915630:-1;chr5:158686913-170909873:-1;chr5:159436934-169458215:1;chr5:162794351-162795869:-1;chr5:163644914-163647267:-1;chr5:164298882-164299192:-1;chr5:168705385-179725835:-1;chr5:169530045-169531333:1;chr5:169530275-169531327:1;chr5:169906818-170836447:1;chr5:172822334-172822667:-1;chr5:172905620-172907360:-1;chr5:173554686-173752658:-1;chr5:175194418-175865733:-1;chr5:176320191-176322792:-1;chr5:176468051-176468499:-1;chr5:177754526-177756462:-1;chr5:177884673-177885333:-1;chr5:177945053-177945334:1;chr5:18909069-18910604:-1;chr5:19411026-19412153:-1;chr5:1977591-1978203:-1;chr5:2004094-2004526:-1;chr5:2021400-2024588:-1;chr5:26146960-26147286:-1;chr5:26832458-26837656:-1;chr5:28968612-28970649:1;chr5:30951280-30951816:-1;chr5:3555327-3555655:-1;chr5:4101955-4108309:-1;chr5:42201690-42203531:-1;chr5:42664312-42666991:-1;chr5:44830753-44831330:-1;chr5:540050-540677:-1;chr5:54944352-54946799:-1;chr5:56166713-114164022:1;chr5:5663790-5664150:-1;chr5:57359235-57369537:-1;chr5:57715754-57721863:-1;chr5:58373474-148118156:-1;chr5:595314-595383:1;chr5:60037465-60039426:-1;chr5:61610539-61612181:-1;chr5:62489429-166310315:1;chr5:62861188-167978751:-1;chr5:63105432-175221785:1;chr5:63106135-120837039:-1;chr5:63366750-74574197:1;chr5:64229493-72809488:-1;chr5:64321826-64322163:-1;chr5:65063855-65066152:-1;chr5:66086160-125278179:1;chr5:67391931-138366134:1;chr5:721073-721603:-1;chr5:73684752-73685070:-1;chr5:74560773-132222253:1;chr5:74577899-94369740:-1;chr5:75858691-140615661:1;chr5:76021776-114004171:1;chr5:76175122-179917612:1;chr5:76573958-180062489:-1;chr5:78347155-171994001:1;chr5:78722803-142414106:-1;chr5:79278986-120629470:1;chr5:79304033-158088173:-1;chr5:81124934-165369510:1;chr5:82192488-82192803:-1;chr5:82518521-82518827:-1;chr5:82941831-82942150:-1;chr5:86281760-86282898:-1;chr5:86638850-103963539:-1;chr5:88067785-88068115:-1;chr5:88078910-88079237:-1;chr5:90535531-90537854:-1;chr5:90850903-92212036:-1;chr5:91244562-142050416:-1;chr5:91246674-164840412:1;chr5:91516543-91516897:-1;chr5:92052113-97106484:1;chr5:94282780-152359924:1;chr5:94790374-151482618:1;chr5:95549202-98054383:-1;chr5:95935487-95935833:-1;chr5:96737004-167058231:1;chr5:98152021-165334473:1;chr5:98153384-146579296:-1;chr5:98229697-98255688:1;chr5:99121222-99121522:1;chr5:99636063-99636375:-1;chr5:99688689-146961983:-1;chr6:100141222-100142042:-1;chr6:102063482-102065089:-1;chr6:102921815-102922506:-1;chr6:105367521-105370452:-1;chr6:107090329-107090648:-1;chr6:108138035-108139095:-1;chr6:11588104-19943851:-1;chr6:11664092-11664412:-1;chr6:116857523-116857842:-1;chr6:119118411-119120619:1;chr6:119118981-119120620:1;chr6:119303689-119304028:1;chr6:122358531-122361741:-1;chr6:124540621-124540944:-1;chr6:129361212-129367271:-1;chr6:131459695-131460680:-1;chr6:131926491-131926654:1;chr6:131926539-131926606:1;chr6:133383519-133389584:-1;chr6:133413194-133413538:-1;chr6:134310673-134311421:-1;chr6:135466929-135887960:-1;chr6:137355387-137355880:-1;chr6:141590317-141591723:-1;chr6:14853260-14853676:-1;chr6:14947451-14949979:-1;chr6:149843626-149844585:-1;chr6:153071676-153075494:-1;chr6:154661698-154663213:-1;chr6:158468258-158469058:-1;chr6:160797741-160876575:1;chr6:165644659-165652125:-1;chr6:167408060-167409592:-1;chr6:169056342-169056410:1;chr6:18510069-18510849:-1;chr6:21255053-21540327:-1;chr6:22160749-22161707:-1;chr6:23408355-23408677:-1;chr6:23767928-52752404:-1;chr6:24919866-24925941:-1;chr6:26851897-26853161:-1;chr6:29793462-29796073:-1;chr6:31102020-31103085:-1;chr6:31301482-31302635:-1;chr6:31319599-31321099:-1;chr6:32421761-32422084:-1;chr6:32485882-32486663:-1;chr6:32622891-32624243:-1;chr6:32669938-32672591:-1;chr6:32784552-32785007:-1;chr6:33134706-33136588:-1;chr6:33201402-33201733:-1;chr6:33233898-33234821:-1;chr6:35734412-35737724:-1;chr6:35862538-35874763:1;chr6:37402950-37403273:-1;chr6:37959204-37960556:-1;chr6:41726813-41727262:-1;chr6:46040628-49403426:-1;chr6:50873930-50874241:-1;chr6:51307435-51308085:-1;chr6:51844070-51844765:-1;chr6:54664408-54664743:-1;chr6:54954347-54959404:-1;chr6:54972337-54972664:-1;chr6:57392870-57397315:-1;chr6:57405149-57409205:-1;chr6:57531030-57537082:-1;chr6:57586116-57586823:-1;chr6:57691648-57698241:-1;chr6:5843448-5843876:-1;chr6:611376-612821:-1;chr6:64724970-64726309:-1;chr6:65767731-65772438:-1;chr6:66316750-66318744:-1;chr6:66651762-66652556:-1;chr6:68158251-68168885:-1;chr6:74922159-74923310:-1;chr6:77154216-77159365:-1;chr6:8282723-8286568:-1;chr6:85374876-85380953:-1;chr6:88342524-88343000:-1;chr6:89978472-89978895:-1;chr6:90510853-90511320:-1;chr6:9381801-9382936:-1;chr6:95250045-95251059:-1;chr6:96959760-96960091:-1;chr6:98523451-98525258:-1;chr7:100388524-100389183:1;chr7:100388721-100389180:1;chr7:100787986-100790532:-1;chr7:100845908-100847017:-1;chr7:101120931-101121251:-1;chr7:102587905-102588625:-1;chr7:1042850-1046369:-1;chr7:108140093-108140418:-1;chr7:113203406-113209452:-1;chr7:1133954-1135670:-1;chr7:1151595-1154185:-1;chr7:118131047-118131402:-1;chr7:125833124-125838685:-1;chr7:127002205-127005217:-1;chr7:128096457-128096775:-1;chr7:130028993-130029283:-1;chr7:133435543-133448872:-1;chr7:134000547-134000970:-1;chr7:134839755-134840089:-1;chr7:135147351-135147987:1;chr7:138392822-138393139:-1;chr7:141726639-141726977:-1;chr7:144547817-144552334:-1;chr7:147703799-147707259:-1;chr7:150093999-150094340:-1;chr7:151876302-151877267:-1;chr7:151912656-151915268:-1;chr7:152050351-152050667:-1;chr7:152339401-152339778:-1;chr7:152941071-152941761:-1;chr7:153784750-153786009:-1;chr7:154079781-154080402:-1;chr7:154301941-154302263:-1;chr7:154507485-154511559:1;chr7:154507930-154511562:1;chr7:154563164-154563452:-1;chr7:155817310-155817557:1;chr7:157722240-157723214:-1;chr7:157739405-157740148:-1;chr7:157911536-157913485:-1;chr7:157938573-157938953:-1;chr7:158193511-158197525:-1;chr7:158802672-158817342:-1;chr7:16138298-16140597:-1;chr7:1996911-1998367:-1;chr7:24004690-24006599:-1;chr7:24224612-24225008:-1;chr7:25011138-25011467:-1;chr7:28540834-28541684:-1;chr7:29654980-29656573:-1;chr7:30243297-30246460:1;chr7:30243348-30246054:1;chr7:31282178-31285607:-1;chr7:31490304-31491792:-1;chr7:32356690-32359637:-1;chr7:36407747-36408521:-1;chr7:37965041-37965356:-1;chr7:42516233-42516555:-1;chr7:42571162-42571504:-1;chr7:45616943-45617182:1;chr7:47675243-47676186:1;chr7:51659403-51659726:-1;chr7:52062468-52062781:-1;chr7:55889630-55890208:1;chr7:62933879-67065292:1;chr7:63953252-63955503:-1;chr7:64050811-64051469:-1;chr7:64525325-64526329:-1;chr7:6488998-6510531:1;chr7:6489013-6510016:1;chr7:64899902-64900224:1;chr7:66769230-66769580:-1;chr7:67364377-67364696:-1;chr7:68100011-68100330:-1;chr7:70849837-70850894:-1;chr7:71908201-71913781:-1;chr7:7508844-7509144:-1;chr7:81196274-81196548:-1;chr7:81279591-81280498:-1;chr7:86674565-86674874:-1;chr7:87929243-87929693:-1;chr7:89648345-89650537:-1;chr7:93254877-93260941:-1;chr7:9601175-9602518:-1;chr7:96313837-96319945:-1;chr8:100226988-100227422:1;chr8:100226997-100227098:1;chr8:104452090-104452410:-1;chr8:108850588-108851597:-1;chr8:109799351-109799676:-1;chr8:110303895-110304228:-1;chr8:110579496-110579818:-1;chr8:112363228-112366316:-1;chr8:114125671-114127951:-1;chr8:115148491-115149852:-1;chr8:116557409-116557738:-1;chr8:119049953-119050304:-1;chr8:119516239-119516550:-1;chr8:120223725-120230398:-1;chr8:120812982-137250528:1;chr8:120969386-120973992:-1;chr8:121993154-139697800:1;chr8:122521642-137377756:1;chr8:122529889-137418279:-1;chr8:126750571-126750902:-1;chr8:127261392-127263756:-1;chr8:128993509-137252236:-1;chr8:129534338-129540451:-1;chr8:1310792-1311710:-1;chr8:132237483-132237796:-1;chr8:135152098-135158200:-1;chr8:137229379-137233082:-1;chr8:137786011-137786337:-1;chr8:138195037-138196763:-1;chr8:138200148-138200363:1;chr8:138200150-138200745:1;chr8:138269358-138269604:-1;chr8:138812149-138813045:-1;chr8:138929979-138930314:-1;chr8:141236326-141236681:-1;chr8:144127988-144128542:-1;chr8:144794759-144795091:-1;chr8:146027877-146028688:-1;chr8:16589796-16590121:-1;chr8:1733872-1734357:-1;chr8:18498900-18500233:-1;chr8:18695738-18696712:-1;chr8:2202865-2203561:1;chr8:2203509-2203685:1;chr8:2467913-2468297:-1;chr8:25122602-25126576:-1;chr8:25910095-26417695:-1;chr8:30511833-30512137:-1;chr8:31690797-31691150:-1;chr8:32799551-32810807:-1;chr8:33278322-33279918:-1;chr8:35728269-35732521:-1;chr8:37170040-37171014:-1;chr8:38981239-38981579:1;chr8:40588892-40589541:-1;chr8:41671874-41677291:-1;chr8:42309626-42313589:-1;chr8:52223562-52223873:-1;chr8:53863517-53864182:-1;chr8:54285106-54286202:-1;chr8:56270256-56270613:-1;chr8:60297813-60299085:1;chr8:62198100-62198422:-1;chr8:63092705-63093017:-1;chr8:70520182-70520495:-1;chr8:71746114-71747202:-1;chr8:72713972-72714306:-1;chr8:73950324-73956382:-1;chr8:75525426-75529517:-1;chr8:76289457-76289781:-1;chr8:77499940-77500985:-1;chr8:85201639-85203081:-1;chr8:87257368-87262863:-1;chr8:91009689-91044879:1;chr8:94141519-94146368:-1;chr8:98664585-98664924:-1;chr8:98852637-98852969:-1;chr9:100348869-100351490:-1;chr9:10302842-10319193:1;chr9:103259526-103260209:-1;chr9:103483791-103484557:-1;chr9:10394564-10395094:-1;chr9:105608071-105609550:-1;chr9:106856457-106857169:1;chr9:106856800-106857162:1;chr9:109577352-109580427:-1;chr9:1099966-2824026:-1;chr9:110495891-111130088:1;chr9:113942180-113942495:-1;chr9:115334080-124724345:-1;chr9:121571666-121571984:-1;chr9:12546844-12549657:-1;chr9:130596572-130597537:-1;chr9:130740797-130742029:-1;chr9:131066521-131067905:-1;chr9:134748910-134749954:1;chr9:134748911-134750089:1;chr9:135050549-135050866:-1;chr9:135443489-135443656:1;chr9:135615015-135616088:-1;chr9:135682289-135683441:-1;chr9:137353887-137357427:-1;chr9:137618924-137620023:-1;chr9:139287972-139288108:1;chr9:139683588-139683851:1;chr9:15805309-15811943:-1;chr9:22544006-22544224:1;chr9:22989503-22989835:-1;chr9:23352801-23367685:-1;chr9:24898453-24898664:1;chr9:26502938-26503253:-1;chr9:2804057-2804257:1;chr9:29082577-29088017:-1;chr9:29614709-29615030:-1;chr9:310135-312453:-1;chr9:33413367-33414660:-1;chr9:34671480-34671976:1;chr9:35793108-35793401:-1;chr9:36352905-36354103:-1;chr9:36413664-36413980:-1;chr9:4336671-4336982:-1;chr9:5631633-5632811:-1;chr9:66598312-66601571:-1;chr9:6690556-6700676:-1;chr9:6878787-6879101:-1;chr9:697544-698285:-1;chr9:70927942-70933176:-1;chr9:70994347-70994821:-1;chr9:71085301-71086461:-1;chr9:78109383-78111910:-1;chr9:80019321-80020707:-1;chr9:82377577-82377899:1;chr9:83514183-83516761:-1;chr9:83666906-83667238:-1;chr9:90048816-90050796:-1;chr9:93435638-93443120:-1;chr9:93804424-94201127:-1;chr9:95510176-95511286:-1;chr9:9940442-9940772:-1;chr9:99800896-99801226:-1;chrX:114734790-114735443:-1;chrX:1158621-1158865:1;chrX:11635287-11641334:-1;chrX:126425444-126430080:-1;chrX:134816011-134816398:1;chrX:134985665-134985996:-1;chrX:138212577-138212903:-1;chrX:143234659-143237658:-1;chrX:144229769-144232200:-1;chrX:150170668-150171038:-1;chrX:16337607-16338140:-1;chrX:17430551-17430866:-1;chrX:22582499-22582814:-1;chrX:353783-354139:1;chrX:40390124-40390448:-1;chrX:45472512-45472819:-1;chrX:47976656-47977943:-1;chrX:5065347-5067503:-1;chrX:52903445-55695675:1;chrX:52904508-52906781:-1;chrX:52908843-55695834:1;chrX:67139835-67140092:1;chrX:67266711-67272075:-1;chrX:77008281-77010767:-1;chrX:77583512-77584110:-1;chrX:78833104-78835492:-1;chrX:819493-819981:-1;chrX:85491836-85496528:-1;chrX:93896385-125317620:-1;chrX:94937503-94938136:-1 hs1:815629-815629,hs1:5649523-5649523;hs1:816163-816163,hs1:5650075-5650075;hs1:816176-816176,hs1:5650768-5650768;hs1:5650266-5650266,hs1:5650895-5650895;hs1:8706415-8706415,hs8:145491742-145491742;hs1:8706521-8706521,hs3:23338239-23338239;hs1:8707439-8707439,hs3:23338260-23338260;hs1:14308895-14308895,hs1:14310828-14310828;hs1:14309661-14309661,hs1:14311528-14311528;hs1:16924310-16924310,hs1:232978810-232978810;hs1:17058516-17058516,hs1:144094017-144094017;hs1:29593426-29593426,hs1:30651405-30651405;hs1:31744128-31744128,hs1:31744235-31744235;hs1:34874009-34874009,hs1:34884564-34884564;hs1:80567211-80567211,hs1:80567703-80567703;hs1:85521222-85521222,hs1:85521552-85521552;hs1:143607654-143607654,hs1:143612403-143612403;hs1:143607654-143607654,hs1:143618166-143618166;hs1:143612537-143612537,hs1:143618166-143618166;hs1:152690581-152690581,hs1:152691707-152691707;hs1:152813228-152813228,hs1:152816292-152816292;hs1:152995359-152995359,hs1:153002302-153002302;hs1:153263215-153263215,hs1:153263742-153263742;hs1:154452854-154452854,hs8:47059554-47059554;hs1:166452809-166452809,hs1:180540938-180540938;hs1:183639729-183639729,hs1:183640067-183640067;hs1:183639729-183639729,hs1:183640067-183640067;hs1:185092795-185092795,hs1:185093003-185093003;hs1:196023411-196023411,hs1:196024608-196024608;hs1:196023411-196023411,hs1:196024609-196024609;hs1:203445283-203445283,hs1:203445427-203445427;hs1:203445294-203445294,hs1:203445416-203445416;hs1:204029973-204029973,hs1:204072495-204072495;hs1:216852553-216852553,hs1:216852873-216852873;hs1:216852553-216852553,hs1:216852873-216852873;hs1:222459457-222459457,hs1:222459770-222459770;hs1:222459457-222459457,hs1:222459770-222459770;hs1:235632726-235632726,hs1:235632830-235632830;hs1:235632729-235632729,hs1:235632827-235632827;hs1:244221730-244221730,hs1:244222266-244222266;hs1:244222543-244222543,hs1:244222919-244222919;hs10:6137380-6137380,hs10:6137878-6137878;hs10:6292000-6292000,hs10:6292956-6292956;hs10:12907150-12907150,hs10:12907175-12907175;hs10:12907177-12907177,hs10:12907250-12907250;hs10:13144973-13144973,hs10:13145283-13145283;hs10:13145088-13145088,hs10:13145278-13145278;hs10:44742947-44742947,hs10:44744309-44744309;hs10:44743233-44743233,hs10:44743964-44743964;hs10:46443089-46443089,hs10:46479535-46479535;hs10:46508391-46508391,hs10:46508719-46508719;hs10:46508391-46508391,hs10:46508719-46508719;hs10:47124524-47124524,hs10:51159025-51159025;hs10:58927664-58927664,hs10:58927992-58927992;hs10:107242992-107242992,hs10:107243345-107243345;hs10:107242992-107242992,hs10:107243356-107243356;hs10:127180407-127180407,hs10:127180684-127180684;hs10:127180969-127180969,hs10:127187217-127187217;hs10:127181647-127181647,hs10:127187226-127187226;hs10:128096467-128096467,hs10:128096781-128096781;hs11:1006740-1006740,hs11:1007919-1007919;hs11:1871843-1871843,hs11:1893531-1893531;hs11:7673491-7673491,hs11:7673807-7673807;hs11:12109134-12109134,hs11:12109458-12109458;hs11:12109134-12109134,hs11:12109458-12109458;hs11:12496264-12496264,hs11:16968372-16968372;hs11:46854216-46854216,hs17:34728891-34728891;hs11:47138085-47138085,hs17:37118636-37118636;hs11:47842443-47842443,hs11:47844310-47844310;hs11:47844413-47844413,hs17:37124712-37124712;hs11:47866065-47866065,hs17:34086941-34086941;hs11:47866069-47866069,hs11:47873648-47873648;hs11:47873992-47873992,hs17:37118529-37118529;hs11:48076641-48076641,hs11:48076950-48076950;hs11:48076647-48076647,hs11:48076956-48076956;hs11:62591284-62591284,hs11:62828886-62828886;hs11:63936450-63936450,hs11:64021660-64021660;hs11:63979419-63979419,hs11:63980089-63980089;hs11:65775274-65775274,hs11:65776457-65776457;hs11:65775568-65775568,hs11:65776578-65776578;hs11:69367633-69367633,hs11:69368139-69368139;hs11:69367911-69367911,hs11:69368231-69368231;hs11:93711796-93711796,hs22:27395765-27395765;hs11:95872780-95872780,hs11:95873092-95873092;hs11:95872780-95872780,hs11:95873092-95873092;hs11:97769809-97769809,hs11:97774197-97774197;hs11:97769812-97769812,hs11:97774201-97774201;hs11:99195693-99195693,hs11:99196517-99196517;hs11:100949824-100949824,hs11:100950662-100950662;hs11:126007804-126007804,hs11:126007877-126007877;hs12:1101129-1101129,hs12:1102060-1102060;hs12:10623400-10623400,hs12:10623557-10623557;hs12:12436120-12436120,hs12:12437888-12437888;hs12:12436200-12436200,hs12:12437784-12437784;hs12:20350912-20350912,hs12:105188605-105188605;hs12:25847393-25847393,hs12:102883840-102883840;hs12:25847393-25847393,hs12:124367100-124367100;hs12:27986914-27986914,hs12:27986991-27986991;hs12:29464687-29464687,hs12:29465028-29465028;hs12:90145434-90145434,hs12:103828063-103828063;hs12:92882475-92882475,hs12:92882787-92882787;hs12:102883759-102883759,hs12:124367100-124367100;hs12:102883968-102883968,hs12:102897736-102897736;hs12:102906672-102906672,hs12:124367117-124367117;hs12:109100971-109100971,hs12:109102205-109102205;hs12:122022440-122022440,hs21:39469239-39469239;hs12:122022525-122022525,hs16:83577779-83577779;hs12:126957018-126957018,hs12:126957892-126957892;hs13:20627290-20627290,hs13:20627832-20627832;hs13:20627290-20627290,hs13:20630060-20630060;hs13:20628336-20628336,hs13:20630043-20630043;hs13:20630265-20630265,hs13:20640126-20640126;hs13:20632127-20632127,hs13:20640126-20640126;hs13:20634016-20634016,hs13:20640128-20640128;hs13:20640540-20640540,hs13:20644479-20644479;hs13:20640540-20640540,hs13:20648512-20648512;hs13:77180002-77180002,hs13:85510791-85510791;hs13:77182042-77182042,hs13:85542319-85542319;hs13:81254873-81254873,hs13:81254960-81254960;hs13:81254877-81254877,hs13:81254977-81254977;hs13:94615720-94615720,hs17:38136678-38136678;hs13:95405344-95405344,hs17:4472181-4472181;hs13:95722291-95722291,hs17:37124710-37124710;hs13:96010422-96010422,hs17:34324703-34324703;hs13:102729647-102729647,hs13:102729962-102729962;hs13:102729653-102729653,hs13:102729968-102729968;hs13:107364484-107364484,hs13:107365373-107365373;hs13:108471208-108471208,hs13:108471947-108471947;hs14:20605984-20605984,hs14:20606310-20606310;hs14:33359799-33359799,hs14:33360138-33360138;hs14:62856932-62856932,hs14:62857264-62857264;hs14:62856932-62856932,hs14:62857264-62857264;hs14:64358740-64358740,hs14:64358845-64358845;hs14:69440386-69440386,hs14:89981782-89981782;hs14:75883534-75883534,hs14:75883967-75883967;hs14:75883534-75883534,hs14:75883967-75883967;hs14:92995777-92995777,hs14:92996259-92996259;hs14:105843008-105843008,hs15:19992793-19992793;hs15:20642766-20642766,hs15:20643017-20643017;hs15:43855272-43855272,hs15:43855622-43855622;hs15:43855272-43855272,hs15:43855622-43855622;hs15:56366803-56366803,hs22:44119634-44119634;hs15:56366803-56366803,hs22:44120340-44120340;hs15:56367428-56367428,hs15:57729146-57729146;hs15:56367467-56367467,hs22:44683465-44683465;hs15:56368358-56368358,hs22:44887445-44887445;hs15:57500190-57500190,hs15:57500521-57500521;hs15:57729048-57729048,hs22:44683465-44683465;hs15:58421467-58421467,hs22:44734518-44734518;hs15:69672525-69672525,hs15:69672863-69672863;hs15:69672529-69672529,hs15:69672867-69672867;hs15:70650092-70650092,hs22:20419967-20419967;hs15:75697926-75697926,hs15:75698300-75698300;hs15:75697927-75697927,hs15:75698301-75698301;hs15:77678911-77678911,hs15:77679236-77679236;hs15:77678911-77678911,hs15:77679236-77679236;hs15:88974980-88974980,hs15:88975313-88975313;hs15:88974994-88974994,hs15:88975327-88975327;hs15:89782584-89782584,hs15:89790272-89790272;hs16:14488376-14488376,hs16:33857677-33857677;hs16:14488492-14488492,hs16:33857179-33857179;hs16:21501943-21501943,hs16:22618252-22618252;hs16:33829643-33829643,hs16:33830566-33830566;hs16:33852431-33852431,hs16:33852872-33852872;hs16:33857196-33857196,hs16:33857588-33857588;hs16:33860096-33860096,hs16:33863532-33863532;hs16:33868976-33868976,hs20:26137105-26137105;hs16:47208373-47208373,hs16:47208826-47208826;hs16:47462793-47462793,hs16:47463727-47463727;hs16:47463311-47463311,hs16:47463739-47463739;hs16:65702685-65702685,hs21:41775590-41775590;hs16:65702689-65702689,hs16:66265338-66265338;hs16:66265351-66265351,hs21:38798283-38798283;hs16:69721878-69721878,hs16:69722205-69722205;hs16:83303848-83303848,hs16:83583663-83583663;hs16:83583518-83583518,hs17:71300430-71300430;hs17:13161223-13161223,hs17:13161550-13161550;hs17:13161223-13161223,hs17:13161550-13161550;hs17:22287173-22287173,hs17:22289165-22289165;hs17:29008729-29008729,hs17:29009871-29009871;hs17:34684329-34684329,hs17:37128609-37128609;hs17:34684329-34684329,hs17:37128609-37128609;hs17:34684357-34684357,hs17:37128599-37128599;hs17:34684358-34684358,hs17:34684631-34684631;hs17:34701681-34701681,hs17:34786237-34786237;hs17:37128608-37128608,hs17:37128716-37128716;hs17:38734829-38734829,hs17:38756586-38756586;hs17:38737115-38737115,hs17:38819095-38819095;hs17:38739015-38739015,hs17:38821536-38821536;hs17:42569727-42569727,hs17:42571105-42571105;hs17:42569727-42569727,hs17:42574216-42574216;hs17:42571256-42571256,hs17:42574595-42574595;hs17:42574391-42574391,hs17:42576250-42576250;hs17:42574803-42574803,hs17:42587036-42587036;hs17:42574803-42574803,hs17:42589277-42589277;hs17:42576345-42576345,hs17:42589277-42589277;hs17:42587144-42587144,hs17:42589274-42589274;hs17:42589489-42589489,hs17:42590569-42590569;hs17:42589747-42589747,hs17:42602281-42602281;hs17:42590669-42590669,hs17:42621509-42621509;hs17:71299981-71299981,hs21:39469181-39469181;hs18:11499265-11499265,hs18:11501290-11501290;hs18:11499274-11499274,hs18:11501465-11501465;hs18:11499708-11499708,hs18:11501477-11501477;hs18:35315644-35315644,hs18:35315974-35315974;hs18:41515012-41515012,hs18:41515337-41515337;hs18:43353906-43353906,hs18:43354218-43354218;hs18:61684234-61684234,hs18:61684578-61684578;hs18:74098284-74098284,hs18:74098616-74098616;hs19:4690147-4690147,hs19:4690702-4690702;hs19:14567528-14567528,hs19:14567835-14567835;hs19:15647018-15647018,hs19:15749478-15749478;hs19:19012944-19012944,hsX:48100202-48100202;hs19:23933594-23933594,hs19:23934249-23934249;hs19:49573810-49573810,hs19:49574365-49574365;hs19:56867749-56867749,hs19:56869333-56869333;hs2:1514350-1514350,hs2:1515203-1515203;hs2:9841660-9841660,hs15:56972851-56972851;hs2:9849353-9849353,hs14:73460747-73460747;hs2:16269873-16269873,hs2:16271469-16271469;hs2:16269891-16269891,hs2:16269986-16269986;hs2:16269891-16269891,hs2:16271245-16271245;hs2:20530159-20530159,hs2:20530466-20530466;hs2:25105754-25105754,hs14:73460751-73460751;hs2:25108333-25108333,hs15:56972840-56972840;hs2:33618082-33618082,hs2:33618766-33618766;hs2:33618126-33618126,hs2:33621381-33621381;hs2:64560660-64560660,hs3:5696331-5696331;hs2:64560664-64560664,hs3:124032533-124032533;hs2:69613870-69613870,hs2:236016542-236016542;hs2:69613873-69613873,hs3:5696353-5696353;hs2:70319316-70319316,hs2:236016864-236016864;hs2:70319354-70319354,hs2:236321158-236321158;hs2:70327063-70327063,hs3:124032335-124032335;hs2:70327110-70327110,hs2:236321212-236321212;hs2:70377107-70377107,hs2:179004386-179004386;hs2:70377130-70377130,hs2:179024142-179024142;hs2:89411544-89411544,hs22:15775699-15775699;hs2:91114562-91114562,hs2:91123493-91123493;hs2:94907460-94907460,hsY:11768327-11768327;hs2:96837688-96837688,hs3:123626512-123626512;hs2:96838646-96838646,hs2:205452441-205452441;hs2:98569472-98569472,hs2:234413243-234413243;hs2:99791680-99791680,hs13:108471209-108471209;hs2:99791973-99791973,hs13:108471947-108471947;hs2:132733902-132733902,hs2:132735119-132735119;hs2:132743136-132743136,hs2:132747162-132747162;hs2:132759623-132759623,hs2:161843512-161843512;hs2:134260748-134260748,hs2:134261080-134261080;hs2:134260761-134260761,hs2:134261093-134261093;hs2:161843310-161843310,hs2:161847428-161847428;hs2:179005229-179005229,hs2:179009119-179009119;hs2:179005229-179005229,hs2:179014582-179014582;hs2:179005229-179005229,hs2:179016238-179016238;hs2:179009292-179009292,hs2:179020481-179020481;hs2:179014872-179014872,hs2:179016994-179016994;hs2:179015166-179015166,hs2:179020284-179020284;hs2:182273500-182273500,hs2:182273828-182273828;hs2:182273509-182273509,hs2:182273837-182273837;hs2:195923061-195923061,hs2:195923473-195923473;hs2:195923061-195923061,hs2:195923473-195923473;hs2:201854903-201854903,hs2:201857695-201857695;hs2:205451493-205451493,hs2:205452458-205452458;hs2:206439444-206439444,hs2:206439767-206439767;hs2:206439444-206439444,hs2:206439767-206439767;hs2:219760799-219760799,hs2:219764477-219764477;hs2:225001195-225001195,hs2:225001331-225001331;hs2:225001195-225001195,hs2:225002195-225002195;hs2:225001224-225001224,hs2:225002195-225002195;hs2:233118125-233118125,hs2:234413098-234413098;hs20:6098959-6098959,hs20:6099291-6099291;hs20:23051303-23051303,hs20:23051632-23051632;hs20:23051303-23051303,hs20:23051632-23051632;hs20:26136787-26136787,hsY:10644116-10644116;hs20:26158907-26158907,hs20:26159109-26159109;hs20:28252473-28252473,hs20:28254885-28254885;hs20:32579492-32579492,hs20:32579825-32579825;hs20:32579492-32579492,hs20:32579825-32579825;hs20:45956869-45956869,hs20:45957138-45957138;hs20:52726066-52726066,hs20:52726380-52726380;hs20:52726072-52726072,hs20:52726386-52726386;hs21:10058041-10058041,hs21:10058608-10058608;hs21:10111765-10111765,hs21:10114519-10114519;hs21:22548076-22548076,hs21:28215431-28215431;hs21:26296029-26296029,hs21:26296570-26296570;hs21:26296029-26296029,hs21:26296571-26296571;hs21:26942554-26942554,hs21:26943596-26943596;hs21:26942558-26942558,hs21:26943494-26943494;hs21:38798223-38798223,hs21:41779892-41779892;hs21:41775625-41775625,hs21:41786403-41786403;hs21:41779386-41779386,hs21:41793822-41793822;hs21:42099000-42099000,hs21:42099299-42099299;hs21:42099371-42099371,hs21:42100485-42100485;hs21:42099808-42099808,hs21:42100434-42100434;hs22:31625772-31625772,hs22:31626090-31626090;hs22:31625772-31625772,hs22:31626090-31626090;hs22:44119822-44119822,hs22:44120329-44120329;hs3:10372475-10372475,hs3:10372834-10372834;hs3:10372475-10372475,hs3:10372834-10372834;hs3:20388456-20388456,hs3:20391911-20391911;hs3:20388456-20388456,hs3:20392237-20392237;hs3:20391506-20391506,hs3:20392068-20392068;hs3:20391506-20391506,hs3:20392538-20392538;hs3:20391916-20391916,hs3:20392354-20392354;hs3:33048131-33048131,hs17:22921931-22921931;hs3:41337146-41337146,hs3:41338115-41338115;hs3:41337155-41337155,hs3:41338800-41338800;hs3:43666852-43666852,hs3:57815633-57815633;hs3:49469290-49469290,hs3:49469619-49469619;hs3:49469291-49469291,hs3:49469620-49469620;hs3:75779122-75779122,hs3:75779615-75779615;hs3:75876975-75876975,hs3:75884495-75884495;hs3:134331397-134331397,hs3:134331559-134331559;hs3:147867880-147867880,hs3:147873094-147873094;hs3:147867880-147867880,hs3:147877553-147877553;hs3:147873094-147873094,hs3:147877855-147877855;hs3:164008436-164008436,hs3:164030335-164030335;hs3:164028056-164028056,hs3:164030352-164030352;hs3:182980061-182980061,hs3:182981094-182981094;hs3:193338792-193338792,hs3:193339130-193339130;hs3:193338792-193338792,hs3:193339130-193339130;hs4:3568509-3568509,hs4:3597326-3597326;hs4:31709775-31709775,hs4:31714939-31714939;hs4:31714939-31714939,hs4:31718506-31718506;hs4:33523565-33523565,hs4:33524623-33524623;hs4:59627154-59627154,hs4:59633196-59633196;hs4:62854706-62854706,hs6:34810889-34810889;hs4:64414703-64414703,hs4:73309830-73309830;hs4:73246399-73246399,hs4:73310657-73310657;hs4:73299050-73299050,hs4:73299625-73299625;hs4:73299631-73299631,hs6:33327280-33327280;hs4:75101900-75101900,hs4:75102833-75102833;hs4:81107081-81107081,hs4:81113126-81113126;hs4:81273525-81273525,hs4:189905702-189905702;hs4:89066187-89066187,hs4:89077723-89077723;hs4:92150580-92150580,hs4:92154860-92154860;hs4:92152881-92152881,hs4:92155124-92155124;hs4:94526954-94526954,hs7:47885222-47885222;hs4:94526970-94526970,hs7:47885250-47885250;hs4:163324523-163324523,hs4:172573884-172573884;hs4:163918442-163918442,hs4:174047361-174047361;hs4:187461554-187461554,hs4:187817332-187817332;hs4:187717096-187717096,hs14:60071079-60071079;hs4:189878947-189878947,hs4:189905711-189905711;hs4:190528425-190528425,hs4:190528744-190528744;hs4:190772349-190772349,hs4:190772493-190772493;hs4:190772350-190772350,hs4:190775450-190775450;hs4:190772393-190772393,hs4:190774024-190774024;hs4:190772499-190772499,hs4:190773924-190773924;hs4:190772499-190772499,hs4:190775357-190775357;hs4:190822807-190822807,hs4:190850110-190850110;hs4:190844038-190844038,hs4:190847299-190847299;hs4:191129482-191129482,hs4:191129918-191129918;hs5:1716916-1716916,hs5:1717334-1717334;hs5:4088042-4088042,hs5:4088926-4088926;hs5:9464774-9464774,hs5:9465088-9465088;hs5:9464774-9464774,hs5:9465088-9465088;hs5:10809182-10809182,hs5:10809517-10809517;hs5:10809182-10809182,hs5:10809517-10809517;hs5:17652609-17652609,hs5:17666707-17666707;hs5:17653642-17653642,hs5:17703289-17703289;hs5:25857539-25857539,hs5:25859705-25859705;hs5:25859705-25859705,hs5:25862759-25862759;hs5:29105073-29105073,hs5:29105383-29105383;hs5:41464481-41464481,hs8:111701779-111701779;hs5:52549496-52549496,hs6:45075158-45075158;hs5:52812955-52812955,hs5:143453540-143453540;hs5:52910533-52910533,hs5:56172365-56172365;hs5:53212698-53212698,hs5:53213003-53213003;hs5:54856364-54856364,hs5:155098262-155098262;hs5:58502981-58502981,hs5:173341961-173341961;hs5:58675619-58675619,hs5:93092171-93092171;hs5:60392532-60392532,hs5:66107209-66107209;hs5:61554823-61554823,hs5:176715412-176715412;hs5:61972489-61972489,hs5:170112594-170112594;hs5:61972645-61972645,hs5:91970667-91970667;hs5:61972991-61972991,hs5:86652629-86652629;hs5:61973297-61973297,hs5:64913536-64913536;hs5:61973430-61973430,hs5:163958106-163958106;hs5:63102228-63102228,hs5:131105487-131105487;hs5:63102228-63102228,hs5:170068659-170068659;hs5:63102560-63102560,hs5:174610344-174610344;hs5:63102903-63102903,hs5:92709074-92709074;hs5:63477011-63477011,hs5:64922226-64922226;hs5:63477741-63477741,hs5:169372143-169372143;hs5:63719928-63719928,hs5:113531443-113531443;hs5:64227550-64227550,hs5:107556166-107556166;hs5:64227550-64227550,hs5:168455384-168455384;hs5:64357076-64357076,hs5:71526608-71526608;hs5:64476372-64476372,hs5:126215447-126215447;hs5:64476372-64476372,hs5:146138232-146138232;hs5:64650978-64650978,hs5:98686785-98686785;hs5:64701582-64701582,hs5:126846230-126846230;hs5:64708385-64708385,hs5:165512529-165512529;hs5:64908703-64908703,hs5:129219573-129219573;hs5:64913538-64913538,hs5:86652643-86652643;hs5:64922214-64922214,hs5:147615126-147615126;hs5:64922642-64922642,hs5:67139400-67139400;hs5:64922700-64922700,hs5:174610011-174610011;hs5:66088639-66088639,hs5:121185240-121185240;hs5:66297160-66297160,hs5:100992961-100992961;hs5:66980579-66980579,hs5:79885815-79885815;hs5:66980579-66980579,hs5:143977903-143977903;hs5:67051195-67051195,hs5:157422785-157422785;hs5:67138965-67138965,hs5:98042019-98042019;hs5:71526606-71526606,hs5:170289507-170289507;hs5:71526679-71526679,hs5:112420418-112420418;hs5:71526940-71526940,hs5:158171860-158171860;hs5:71527592-71527592,hs5:154905925-154905925;hs5:71527592-71527592,hs5:158171909-158171909;hs5:72768497-72768497,hs5:169198543-169198543;hs5:72776148-72776148,hs5:145921383-145921383;hs5:72790237-72790237,hs5:111369299-111369299;hs5:72790643-72790643,hs5:102910340-102910340;hs5:72790860-72790860,hs5:155631650-155631650;hs5:72791339-72791339,hs5:142805859-142805859;hs5:72791339-72791339,hs5:155490981-155490981;hs5:72791339-72791339,hs5:168933823-168933823;hs5:72810492-72810492,hs5:73140412-73140412;hs5:73140022-73140022,hs5:180207838-180207838;hs5:73797429-73797429,hs5:98348694-98348694;hs5:74558980-74558980,hs5:110183061-110183061;hs5:74576896-74576896,hs5:123906035-123906035;hs5:75240831-75240831,hs5:180521716-180521716;hs5:75262662-75262662,hs5:98019609-98019609;hs5:75263533-75263533,hs5:117495245-117495245;hs5:75865836-75865836,hs5:174088271-174088271;hs5:76028784-76028784,hs5:157996861-157996861;hs5:76028784-76028784,hs5:178166306-178166306;hs5:76543875-76543875,hs5:112170684-112170684;hs5:76544538-76544538,hs5:176287614-176287614;hs5:78313495-78313495,hs5:78313814-78313814;hs5:78313929-78313929,hs5:92747900-92747900;hs5:78313930-78313930,hs5:155632924-155632924;hs5:78373644-78373644,hs5:78619022-78619022;hs5:78709079-78709079,hs5:82949445-82949445;hs5:79035428-79035428,hs5:158515026-158515026;hs5:80395338-80395338,hs5:165353857-165353857;hs5:80396854-80396854,hs5:158561984-158561984;hs5:80535963-80535963,hs5:86977967-86977967;hs5:80598450-80598450,hs5:166240670-166240670;hs5:81121895-81121895,hs5:129543328-129543328;hs5:81122412-81122412,hs5:169587393-169587393;hs5:81122606-81122606,hs5:167798662-167798662;hs5:81127694-81127694,hs5:169242749-169242749;hs5:81128796-81128796,hs5:166235954-166235954;hs5:81131238-81131238,hs5:135783831-135783831;hs5:81749093-81749093,hs5:179075590-179075590;hs5:81749539-81749539,hs5:152992487-152992487;hs5:81750732-81750732,hs5:180571480-180571480;hs5:81750875-81750875,hs5:174202167-174202167;hs5:82947897-82947897,hs5:168704325-168704325;hs5:83042435-83042435,hs5:173931953-173931953;hs5:83183013-83183013,hs5:91970077-91970077;hs5:83183031-83183031,hs5:169589830-169589830;hs5:83183388-83183388,hs5:167799477-167799477;hs5:83183411-83183411,hs5:169589539-169589539;hs5:83183543-83183543,hs5:163958050-163958050;hs5:83183592-83183592,hs5:91828074-91828074;hs5:83187478-83187478,hs5:103991047-103991047;hs5:83187792-83187792,hs5:95592720-95592720;hs5:83755771-83755771,hs5:144450820-144450820;hs5:83756106-83756106,hs5:170114449-170114449;hs5:86404260-86404260,hs5:112880257-112880257;hs5:86642181-86642181,hs5:110537807-110537807;hs5:86642527-86642527,hs5:163891769-163891769;hs5:86652328-86652328,hs5:176937270-176937270;hs5:86652625-86652625,hs5:163961593-163961593;hs5:86652659-86652659,hs5:165368292-165368292;hs5:86652659-86652659,hs5:168159783-168159783;hs5:86977387-86977387,hs5:92708948-92708948;hs5:86977666-86977666,hs5:91970848-91970848;hs5:86978136-86978136,hs5:86981663-86981663;hs5:86981178-86981178,hs5:159481740-159481740;hs5:87496378-87496378,hs5:170113128-170113128;hs5:87496840-87496840,hs5:169586581-169586581;hs5:87633907-87633907,hs5:166038136-166038136;hs5:87634039-87634039,hs5:175219409-175219409;hs5:89446360-89446360,hs5:142805669-142805669;hs5:89446360-89446360,hs5:155490866-155490866;hs5:89446360-89446360,hs5:168933914-168933914;hs5:89902239-89902239,hs5:102912278-102912278;hs5:89902533-89902533,hs5:91636632-91636632;hs5:89902533-89902533,hs5:163891425-163891425;hs5:89902701-89902701,hs5:101792512-101792512;hs5:89903154-89903154,hs5:111368386-111368386;hs5:90251782-90251782,hs5:112577542-112577542;hs5:90251782-90251782,hs5:129977126-129977126;hs5:90280862-90280862,hs5:147650127-147650127;hs5:90877208-90877208,hs5:157794917-157794917;hs5:90901648-90901648,hs5:157422920-157422920;hs5:91230019-91230019,hs5:91230324-91230324;hs5:91230279-91230279,hs5:154387321-154387321;hs5:91405574-91405574,hs5:136378579-136378579;hs5:91611885-91611885,hs5:122952184-122952184;hs5:91828372-91828372,hs5:174383707-174383707;hs5:91833727-91833727,hs5:150367847-150367847;hs5:91833727-91833727,hs5:167276948-167276948;hs5:91834445-91834445,hs5:178437366-178437366;hs5:91970386-91970386,hs5:92707475-92707475;hs5:91970478-91970478,hs5:167799621-167799621;hs5:91973279-91973279,hs5:147615580-147615580;hs5:91973562-91973562,hs5:170917222-170917222;hs5:92377391-92377391,hs5:115565343-115565343;hs5:92707474-92707474,hs5:172843626-172843626;hs5:92707582-92707582,hs5:169590067-169590067;hs5:92707660-92707660,hs5:111906677-111906677;hs5:92707919-92707919,hs5:157611422-157611422;hs5:92707919-92707919,hs5:168045359-168045359;hs5:92707996-92707996,hs5:170112897-170112897;hs5:92708161-92708161,hs5:161598233-161598233;hs5:92708161-92708161,hs5:163959288-163959288;hs5:92708263-92708263,hs5:169589322-169589322;hs5:92708403-92708403,hs5:159442612-159442612;hs5:92708442-92708442,hs5:176935236-176935236;hs5:92708480-92708480,hs5:170118637-170118637;hs5:92708480-92708480,hs5:178437103-178437103;hs5:92708492-92708492,hs5:177924195-177924195;hs5:92708814-92708814,hs5:119865681-119865681;hs5:92708898-92708898,hs5:159841855-159841855;hs5:92708900-92708900,hs5:170110531-170110531;hs5:92708925-92708925,hs5:129496335-129496335;hs5:92709008-92709008,hs5:92709610-92709610;hs5:92709008-92709008,hs5:176937824-176937824;hs5:92709036-92709036,hs5:169586442-169586442;hs5:92709190-92709190,hs5:180190414-180190414;hs5:92709568-92709568,hs5:111478857-111478857;hs5:92709610-92709610,hs5:176937533-176937533;hs5:92747905-92747905,hs5:155632721-155632721;hs5:92748269-92748269,hs5:178325927-178325927;hs5:93123221-93123221,hs5:180522168-180522168;hs5:93126177-93126177,hs5:170113329-170113329;hs5:93579037-93579037,hs5:144910126-144910126;hs5:93579365-93579365,hs5:162329871-162329871;hs5:95369076-95369076,hs5:95369430-95369430;hs5:95369082-95369082,hs5:95369436-95369436;hs5:95593047-95593047,hs5:102564388-102564388;hs5:95816521-95816521,hs5:170834934-170834934;hs5:95816751-95816751,hs5:146044655-146044655;hs5:95817434-95817434,hs5:133061432-133061432;hs5:96706846-96706846,hs5:98281862-98281862;hs5:96997746-96997746,hs5:159718617-159718617;hs5:97880926-97880926,hs5:112883603-112883603;hs5:97882290-97882290,hs5:167798685-167798685;hs5:97882530-97882530,hs5:170113616-170113616;hs5:98019008-98019008,hs5:100991732-100991732;hs5:98019560-98019560,hs5:117494703-117494703;hs5:98019963-98019963,hs5:105016844-105016844;hs5:98193728-98193728,hs5:146005626-146005626;hs5:98193778-98193778,hs5:146002233-146002233;hs5:98282554-98282554,hs5:107191981-107191981;hs5:98328493-98328493,hs5:125030556-125030556;hs5:98506747-98506747,hs5:124111012-124111012;hs5:98685954-98685954,hs5:100992957-100992957;hs5:100991349-100991349,hs5:159479137-159479137;hs5:102268069-102268069,hs5:164821649-164821649;hs5:102321766-102321766,hs5:169423386-169423386;hs5:102364550-102364550,hs5:169589390-169589390;hs5:102369513-102369513,hs5:176935670-176935670;hs5:102698645-102698645,hs5:170113520-170113520;hs5:102717513-102717513,hs5:158455644-158455644;hs5:102722700-102722700,hs5:147651124-147651124;hs5:103106609-103106609,hs5:119704688-119704688;hs5:105017630-105017630,hs5:166240670-166240670;hs5:105018321-105018321,hs5:121574208-121574208;hs5:106120581-106120581,hs5:133067217-133067217;hs5:106294820-106294820,hs5:168140402-168140402;hs5:106295446-106295446,hs5:135090410-135090410;hs5:106934585-106934585,hs5:160981697-160981697;hs5:106935525-106935525,hs5:126853234-126853234;hs5:107191271-107191271,hs5:121642655-121642655;hs5:107204297-107204297,hs5:152646140-152646140;hs5:107221978-107221978,hs5:140601636-140601636;hs5:107321785-107321785,hs5:107373673-107373673;hs5:107321785-107321785,hs5:180050598-180050598;hs5:107343298-107343298,hs5:126506775-126506775;hs5:107373673-107373673,hs5:180050888-180050888;hs5:107673654-107673654,hs5:136377653-136377653;hs5:107981157-107981157,hs5:113344787-113344787;hs5:110023159-110023159,hs5:157992338-157992338;hs5:110553917-110553917,hs5:158248033-158248033;hs5:110554066-110554066,hs5:134319168-134319168;hs5:111112917-111112917,hs5:169587341-169587341;hs5:111367244-111367244,hs5:170289172-170289172;hs5:111367688-111367688,hs5:157600345-157600345;hs5:111478857-111478857,hs5:169427943-169427943;hs5:111906383-111906383,hs5:145921223-145921223;hs5:111906383-111906383,hs5:170067921-170067921;hs5:112042704-112042704,hs5:121699075-121699075;hs5:112371087-112371087,hs5:154405598-154405598;hs5:112420102-112420102,hs5:163889808-163889808;hs5:112420418-112420418,hs5:158172034-158172034;hs5:112577542-112577542,hs5:129977239-129977239;hs5:112878070-112878070,hs5:113836146-113836146;hs5:112878432-112878432,hs5:166042341-166042341;hs5:112914958-112914958,hs5:133281299-133281299;hs5:113573823-113573823,hs5:167115679-167115679;hs5:113823882-113823882,hs5:178323970-178323970;hs5:113826075-113826075,hs5:157600772-157600772;hs5:113836146-113836146,hs5:145561936-145561936;hs5:113836146-113836146,hs5:162525374-162525374;hs5:113839021-113839021,hs5:158090070-158090070;hs5:114106191-114106191,hs5:154405629-154405629;hs5:114625238-114625238,hs5:172845895-172845895;hs5:114895608-114895608,hs5:159716148-159716148;hs5:114899571-114899571,hs5:158222958-158222958;hs5:115229552-115229552,hs5:169536941-169536941;hs5:115229552-115229552,hs5:176710825-176710825;hs5:115236005-115236005,hs5:162528575-162528575;hs5:115565377-115565377,hs5:158474753-158474753;hs5:116289310-116289310,hs5:143453575-143453575;hs5:116290466-116290466,hs5:140540556-140540556;hs5:116770327-116770327,hs5:179835089-179835089;hs5:116770692-116770692,hs5:116771956-116771956;hs5:117494325-117494325,hs5:121699396-121699396;hs5:117666334-117666334,hs5:169427220-169427220;hs5:117669298-117669298,hs5:178700032-178700032;hs5:119113359-119113359,hs5:163890237-163890237;hs5:119703821-119703821,hs5:166305693-166305693;hs5:119708408-119708408,hs5:176267436-176267436;hs5:119710559-119710559,hs5:129263864-129263864;hs5:119710559-119710559,hs5:167800129-167800129;hs5:120619256-120619256,hs5:130209066-130209066;hs5:120834730-120834730,hs5:178433733-178433733;hs5:121194330-121194330,hs5:157914968-157914968;hs5:121642012-121642012,hs5:164036126-164036126;hs5:121699048-121699048,hs5:136377815-136377815;hs5:121699048-121699048,hs5:169587331-169587331;hs5:121713389-121713389,hs5:180424664-180424664;hs5:123711923-123711923,hs5:159718256-159718256;hs5:123906379-123906379,hs5:143979112-143979112;hs5:124360586-124360586,hs5:174384322-174384322;hs5:124361532-124361532,hs5:158987622-158987622;hs5:124361532-124361532,hs5:161597738-161597738;hs5:124362300-124362300,hs5:130120856-130120856;hs5:124406898-124406898,hs5:145921658-145921658;hs5:124406901-124406901,hs5:163958789-163958789;hs5:124406901-124406901,hs5:167979913-167979913;hs5:126215447-126215447,hs5:146138381-146138381;hs5:126239696-126239696,hs5:128072714-128072714;hs5:126486277-126486277,hs5:126486715-126486715;hs5:126486277-126486277,hs5:126486715-126486715;hs5:126844655-126844655,hs5:173939354-173939354;hs5:127629122-127629122,hs5:157426784-157426784;hs5:127629122-127629122,hs5:180498392-180498392;hs5:129263864-129263864,hs5:167799846-167799846;hs5:129264082-129264082,hs5:163962296-163962296;hs5:129543227-129543227,hs5:143364607-143364607;hs5:129543227-129543227,hs5:169586802-169586802;hs5:129543229-129543229,hs5:165495242-165495242;hs5:129543729-129543729,hs5:158708697-158708697;hs5:129543953-129543953,hs5:170112701-170112701;hs5:129958515-129958515,hs5:129958906-129958906;hs5:130120367-130120367,hs5:148065770-148065770;hs5:130259731-130259731,hs5:170504860-170504860;hs5:131105248-131105248,hs5:170068658-170068658;hs5:135115680-135115680,hs5:178524257-178524257;hs5:135116718-135116718,hs5:158001645-158001645;hs5:135143095-135143095,hs5:135148611-135148611;hs5:135784194-135784194,hs5:170916912-170916912;hs5:135906520-135906520,hs5:169589893-169589893;hs5:135906750-135906750,hs5:174384191-174384191;hs5:136425859-136425859,hs5:179237935-179237935;hs5:136518432-136518432,hs5:180064593-180064593;hs5:137050460-137050460,hs5:137051784-137051784;hs5:137050468-137050468,hs5:137051792-137051792;hs5:138381215-138381215,hs5:158223790-158223790;hs5:140601636-140601636,hs5:162318060-162318060;hs5:142295058-142295058,hs5:164042674-164042674;hs5:142767727-142767727,hs5:152504525-152504525;hs5:143377919-143377919,hs5:145921889-145921889;hs5:143443774-143443774,hs5:162318315-162318315;hs5:143474911-143474911,hs5:157100955-157100955;hs5:143978821-143978821,hs5:144346206-144346206;hs5:144450572-144450572,hs5:180211597-180211597;hs5:144711967-144711967,hs5:158165168-158165168;hs5:144740961-144740961,hs5:165777723-165777723;hs5:144878219-144878219,hs5:169436541-169436541;hs5:144881002-144881002,hs5:179392723-179392723;hs5:145562835-145562835,hs5:158755797-158755797;hs5:145876981-145876981,hs6:30218513-30218513;hs5:145876993-145876993,hs5:147783025-147783025;hs5:145921223-145921223,hs5:170068011-170068011;hs5:145921741-145921741,hs5:167979913-167979913;hs5:146044332-146044332,hs5:170835116-170835116;hs5:146963575-146963575,hs5:173939665-173939665;hs5:147533232-147533232,hs5:147534808-147534808;hs5:147534432-147534432,hs5:147534971-147534971;hs5:147781483-147781483,hs6:30218503-30218503;hs5:148066171-148066171,hs5:148070079-148070079;hs5:148069672-148069672,hs5:161598036-161598036;hs5:148359608-148359608,hs5:180571467-180571467;hs5:148359903-148359903,hs5:152995935-152995935;hs5:148359953-148359953,hs5:160963295-160963295;hs5:148360321-148360321,hs5:172783645-172783645;hs5:148360678-148360678,hs5:156125156-156125156;hs5:148360786-148360786,hs5:152993121-152993121;hs5:150247109-150247109,hs5:169407531-169407531;hs5:150249276-150249276,hs5:154589721-154589721;hs5:150368193-150368193,hs5:167276944-167276944;hs5:150368986-150368986,hs5:165389749-165389749;hs5:152356930-152356930,hs5:167107852-167107852;hs5:152991870-152991870,hs5:174200982-174200982;hs5:152991870-152991870,hs5:174201162-174201162;hs5:152992918-152992918,hs5:173308630-173308630;hs5:152992921-152992921,hs5:152994086-152994086;hs5:152992921-152992921,hs5:174200979-174200979;hs5:152993285-152993285,hs5:180571480-180571480;hs5:152993583-152993583,hs5:174200823-174200823;hs5:152993992-152993992,hs5:168416740-168416740;hs5:152994086-152994086,hs5:174201156-174201156;hs5:152994511-152994511,hs5:154620162-154620162;hs5:152995471-152995471,hs5:168416146-168416146;hs5:152995515-152995515,hs5:179075936-179075936;hs5:152995515-152995515,hs5:180571864-180571864;hs5:152995519-152995519,hs5:160962390-160962390;hs5:154620570-154620570,hs5:160962529-160962529;hs5:154620741-154620741,hs5:173307326-173307326;hs5:154890571-154890571,hs5:154908746-154908746;hs5:154905925-154905925,hs5:158172170-158172170;hs5:154906311-154906311,hs5:154919533-154919533;hs5:156127384-156127384,hs5:174204097-174204097;hs5:156131766-156131766,hs5:158475253-158475253;hs5:156132006-156132006,hs5:174610601-174610601;hs5:157426782-157426782,hs5:180498532-180498532;hs5:157611799-157611799,hs5:176938851-176938851;hs5:157996873-157996873,hs5:178166375-178166375;hs5:158054443-158054443,hs5:160268828-160268828;hs5:158112738-158112738,hs5:158438791-158438791;hs5:158222958-158222958,hs5:173954625-173954625;hs5:158247630-158247630,hs5:174609986-174609986;hs5:158248033-158248033,hs5:161126803-161126803;hs5:158474738-158474738,hs5:168139963-168139963;hs5:158693551-158693551,hs5:180211599-180211599;hs5:158864504-158864504,hs5:170112170-170112170;hs5:158901333-158901333,hs5:169589442-169589442;hs5:158901808-158901808,hs5:180250390-180250390;hs5:158901859-158901859,hs5:170111870-170111870;hs5:158904682-158904682,hs5:169429315-169429315;hs5:158913986-158913986,hs5:176938302-176938302;hs5:159439235-159439235,hs5:180058318-180058318;hs5:159841699-159841699,hs5:170110530-170110530;hs5:160962043-160962043,hs5:180572183-180572183;hs5:160962216-160962216,hs5:160962805-160962805;hs5:160962390-160962390,hs5:168415914-168415914;hs5:160962800-160962800,hs5:180571570-180571570;hs5:160962805-160962805,hs5:168415914-168415914;hs5:160963555-160963555,hs5:173307322-173307322;hs5:161124975-161124975,hs5:162329394-162329394;hs5:161597755-161597755,hs5:166042345-166042345;hs5:161597776-161597776,hs5:162527948-162527948;hs5:161598036-161598036,hs5:161916785-161916785;hs5:162676708-162676708,hs5:170118521-170118521;hs5:163958237-163958237,hs5:169587182-169587182;hs5:163959052-163959052,hs5:167979910-167979910;hs5:165368292-165368292,hs5:168160032-168160032;hs5:165410689-165410689,hs5:165482016-165482016;hs5:165413799-165413799,hs5:165416999-165416999;hs5:166038136-166038136,hs5:175219401-175219401;hs5:166306712-166306712,hs5:174202360-174202360;hs5:167798656-167798656,hs5:169587397-169587397;hs5:167798684-167798684,hs5:170113620-170113620;hs5:167799230-167799230,hs5:167800096-167800096;hs5:168044695-168044695,hs5:170112594-170112594;hs5:169159969-169159969,hs5:172481845-172481845;hs5:169448989-169448989,hs5:180057872-180057872;hs5:169537046-169537046,hs5:176710825-176710825;hs5:169564604-169564604,hs5:176937982-176937982;hs5:169586691-169586691,hs5:170112903-170112903;hs5:169588065-169588065,hs5:169590244-169590244;hs5:169589204-169589204,hs5:170110149-170110149;hs5:169589341-169589341,hs5:174384758-174384758;hs5:169589895-169589895,hs5:174384189-174384189;hs5:169589941-169589941,hs5:170110248-170110248;hs5:170105804-170105804,hs5:170118851-170118851;hs5:170110144-170110144,hs5:174384758-174384758;hs5:170110579-170110579,hs5:170113401-170113401;hs5:170112094-170112094,hs5:180249984-180249984;hs5:170114774-170114774,hs5:176935229-176935229;hs5:170200259-170200259,hs5:178522812-178522812;hs5:172535541-172535541,hs5:175189306-175189306;hs5:172784573-172784573,hs5:174202164-174202164;hs5:172784733-172784733,hs5:180571870-180571870;hs5:173308746-173308746,hs5:174202358-174202358;hs5:173308873-173308873,hs5:180571873-180571873;hs5:173940448-173940448,hs5:174610601-174610601;hs5:174200156-174200156,hs5:176590438-176590438;hs5:174200770-174200770,hs5:179077171-179077171;hs5:174201378-174201378,hs5:179077171-179077171;hs5:176286456-176286456,hs5:180498504-180498504;hs5:176935119-176935119,hs5:176935828-176935828;hs5:177560205-177560205,hs5:180036476-180036476;hs5:179076211-179076211,hs5:180571903-180571903;hs6:414115-414115,hs6:414659-414659;hs6:11076426-11076426,hs6:11077229-11077229;hs6:11181995-11181995,hs6:20755737-20755737;hs6:11182131-11182131,hs6:24446278-24446278;hs6:20115712-20115712,hs11:57492125-57492125;hs6:20285553-20285553,hs9:108385601-108385601;hs6:20371919-20371919,hs6:20605226-20605226;hs6:20602939-20602939,hs6:20605512-20605512;hs6:20604768-20604768,hs6:20605238-20605238;hs6:20659078-20659078,hs9:108495046-108495046;hs6:20666456-20666456,hs9:108502037-108502037;hs6:20727356-20727356,hs6:24467890-24467890;hs6:20923010-20923010,hs6:20923609-20923609;hs6:20923010-20923010,hs9:111199079-111199079;hs6:20923609-20923609,hs9:111199231-111199231;hs6:23793974-23793974,hs6:23794303-23794303;hs6:24270085-24270085,hs9:108437101-108437101;hs6:24466887-24466887,hs9:110584372-110584372;hs6:25755688-25755688,hs6:25755905-25755905;hs6:27697838-27697838,hs17:51286599-51286599;hs6:27740447-27740447,hs11:67799666-67799666;hs6:27833917-27833917,hs6:27835249-27835249;hs6:30210982-30210982,hs6:30222175-30222175;hs6:30217890-30217890,hs6:30219412-30219412;hs6:32558703-32558703,hs6:32666278-32666278;hs6:32562664-32562664,hs6:32649280-32649280;hs6:32568898-32568898,hs6:32576768-32576768;hs6:32569264-32569264,hs6:32576768-32576768;hs6:32577452-32577452,hs6:32615663-32615663;hs6:32588575-32588575,hs6:32589162-32589162;hs6:32603738-32603738,hs6:32646739-32646739;hs6:32702457-32702457,hs6:32704450-32704450;hs6:32728128-32728128,hs6:32827329-32827329;hs6:32732869-32732869,hs6:32733837-32733837;hs6:33255734-33255734,hs6:33257923-33257923;hs6:34807900-34807900,hs6:34809096-34809096;hs6:43321352-43321352,hs6:43326064-43326064;hs6:43328103-43328103,hs6:43351440-43351440;hs6:49623219-49623219,hs6:49624134-49624134;hs6:50192539-50192539,hs6:50193753-50193753;hs6:52759090-52759090,hs6:52760607-52760607;hs6:52760603-52760603,hs6:52799415-52799415;hs6:54032616-54032616,hs6:54036668-54036668;hs6:54032764-54032764,hs6:54042789-54042789;hs6:54036668-54036668,hs6:54042787-54042787;hs6:54888281-54888281,hs6:54888609-54888609;hs6:89980353-89980353,hs6:89980661-89980661;hs6:94797795-94797795,hs6:94798138-94798138;hs6:119459218-119459218,hs6:119459546-119459546;hs6:119459218-119459218,hs6:119459546-119459546;hs6:153790946-153790946,hs6:161126924-161126924;hs6:154488622-154488622,hs6:154488944-154488944;hs7:562216-562216,hs9:115083284-115083284;hs7:572598-572598,hs7:572788-572788;hs7:631367-631367,hs9:124718642-124718642;hs7:661721-661721,hs9:115346799-115346799;hs7:687318-687318,hs9:120360991-120360991;hs7:690814-690814,hs9:114865051-114865051;hs7:695811-695811,hs7:7037633-7037633;hs7:7032332-7032332,hs9:120255862-120255862;hs7:13894752-13894752,hs9:125026711-125026711;hs7:28180828-28180828,hs7:28181192-28181192;hs7:28180829-28180829,hs7:28181193-28181193;hs7:31553296-31553296,hs7:31558520-31558520;hs7:31553554-31553554,hs7:31556796-31556796;hs7:31556796-31556796,hs7:31558520-31558520;hs7:33865381-33865381,hs7:33865712-33865712;hs7:33865381-33865381,hs7:33865712-33865712;hs7:39248885-39248885,hs9:113959296-113959296;hs7:49522621-49522621,hs7:49522939-49522939;hs7:49522621-49522621,hs7:49522939-49522939;hs7:62750187-62750187,hs7:101475691-101475691;hs7:65831385-65831385,hs7:73020021-73020021;hs7:67273208-67273208,hs7:97921137-97921137;hs7:70058905-70058905,hs7:70076821-70076821;hs7:70064120-70064120,hs7:70076816-70076816;hs7:93379752-93379752,hs7:93380475-93380475;hs7:93380475-93380475,hs7:93383946-93383946;hs7:96360692-96360692,hs7:96361020-96361020;hs7:96360692-96360692,hs7:96361020-96361020;hs7:96381218-96381218,hs7:96384534-96384534;hs7:100400459-100400459,hs7:100401199-100401199;hs7:116629253-116629253,hs7:116629564-116629564;hs7:116629253-116629253,hs7:116629564-116629564;hs7:139828055-139828055,hs7:139835689-139835689;hs7:139828327-139828327,hs7:139836887-139836887;hs7:158080571-158080571,hs7:158080740-158080740;hs8:16866251-16866251,hs8:16866621-16866621;hs8:16866251-16866251,hs8:16866621-16866621;hs8:24713813-24713813,hs8:52865927-52865927;hs8:25911691-25911691,hs12:93210753-93210753;hs8:25956265-25956265,hs12:19633800-19633800;hs8:35712502-35712502,hs8:41746283-41746283;hs8:35733895-35733895,hs20:31723038-31723038;hs8:35733895-35733895,hs8:35754948-35754948;hs8:35751430-35751430,hs8:41769099-41769099;hs8:35754948-35754948,hs20:31722782-31722782;hs8:38274986-38274986,hs8:38307010-38307010;hs8:38297802-38297802,hs8:38298492-38298492;hs8:39026627-39026627,hs8:39030703-39030703;hs8:39145422-39145422,hs8:39146819-39146819;hs8:39920673-39920673,hs8:39920766-39920766;hs8:41597728-41597728,hs8:41599613-41599613;hs8:41598059-41598059,hs8:41598838-41598838;hs8:41598059-41598059,hs8:41598838-41598838;hs8:52771758-52771758,hs8:52771983-52771983;hs8:58278874-58278874,hs8:58285598-58285598;hs8:58279451-58279451,hs8:58280825-58280825;hs8:58280822-58280822,hs8:58290572-58290572;hs8:58285600-58285600,hs8:58289981-58289981;hs8:58285605-58285605,hs8:58289986-58289986;hs8:59241015-59241015,hs8:59241351-59241351;hs8:59241018-59241018,hs8:59241354-59241354;hs8:61367551-61367551,hs8:61367868-61367868;hs8:61367551-61367551,hs8:61367868-61367868;hs8:73186173-73186173,hs8:73186418-73186418;hs8:82207573-82207573,hs8:82209179-82209179;hs8:97167254-97167254,hs8:97167606-97167606;hs8:97167264-97167264,hs8:97167616-97167616;hs8:103504783-103504783,hs8:103505063-103505063;hs8:108638506-108638506,hs8:108638790-108638790;hs8:113154612-113154612,hs8:113154942-113154942;hs8:118781983-118781983,hs8:118782314-118782314;hs8:118942919-118942919,hs8:118944518-118944518;hs8:118942919-118942919,hs8:118944774-118944774;hs8:118944399-118944399,hs8:118944778-118944778;hs8:121750866-121750866,hs8:121751185-121751185;hs8:121750866-121750866,hs8:121751185-121751185;hs8:122062249-122062249,hs8:137918607-137918607;hs8:122558592-122558592,hs8:138076265-138076265;hs8:122989896-122989896,hs8:137467023-137467023;hs8:126664306-126664306,hs8:126670319-126670319;hs8:126664307-126664307,hs8:126670320-126670320;hs8:128968305-128968305,hs8:129221714-129221714;hs8:132898421-132898421,hs8:132899455-132899455;hs8:142858882-142858882,hs8:142859000-142859000;hs9:3770631-3770631,hs9:3770957-3770957;hs9:16379401-16379401,hs9:16379737-16379737;hs9:16379407-16379407,hs9:16379743-16379743;hs9:42405991-42405991,hs9:42406117-42406117;hs9:42405991-42405991,hs9:44010660-44010660;hs9:44010660-44010660,hs9:67564237-67564237;hs9:44010661-44010661,hs9:44010787-44010787;hs9:66195511-66195511,hs9:67903916-67903916;hs9:67901310-67901310,hs9:67903828-67903828;hs9:67912226-67912226,hs9:67913632-67913632;hs9:67912561-67912561,hs9:67913635-67913635;hs9:67914447-67914447,hs9:67914753-67914753;hs9:68286395-68286395,hs9:68287398-68287398;hs9:76087958-76087958,hs9:76088209-76088209;hs9:88344377-88344377,hs9:88345750-88345750;hs9:88344377-88344377,hs9:88345766-88345766;hs9:88345662-88345662,hs9:88345767-88345767;hs9:108232169-108232169,hs9:108256064-108256064;hs9:114976918-114976918,hs9:114977213-114977213;hs9:114976918-114976918,hs9:114977213-114977213;hs9:118516896-118516896,hs9:118517230-118517230;hs9:118516898-118516898,hs9:118517232-118517232;hs9:129940624-129940624,hs9:129941899-129941899;hs9:131198490-131198490,hs9:131198957-131198957;hs9:135369043-135369043,hs9:135369385-135369385;hs9:135403926-135403926,hs9:135404250-135404250;hs9:135403937-135403937,hs9:135404261-135404261;hs9:139892490-139892490,hs9:139897015-139897015;hs9:139893433-139893433,hs9:139897017-139897017;hsX:2709476-2709476,hsX:2709598-2709598;hsX:29179069-29179069,hsX:29180119-29180119;hsX:55189472-55189472,hsX:55202293-55202293;hsX:55565754-55565754,hsX:67262958-67262958;hsX:55569150-55569150,hsX:55570232-55570232;hsX:65944801-65944801,hsX:65945770-65945770;hsX:66182841-66182841,hsX:66185133-66185133;hsX:66994190-66994190,hsX:66995534-66995534;hsY:10629089-10629089,hsY:10632012-10632012;hsY:10639950-10639950,hsY:10641232-10641232;hsY:11714592-11714592,hsY:11715838-11715838;hsY:11764075-11764075,hsY:11783506-11783506;hsY:11923514-11923514,hsY:11938155-11938155;hsY:11924661-11924661,hsY:11950110-11950110;hsY:11924877-11924877,hsY:11939594-11939594;hsY:11932544-11932544,hsY:11949955-11949955;hsY:11937049-11937049,hsY:11947822-11947822;hsY:11939293-11939293,hsY:11950065-11950065;hsY:11948404-11948404,hsY:11949665-11949665;hsY:57392793-57392793,hsY:57397707-57397707 The VCaP cell line is widely used in prostate cancer research as it is a unique model to study castrate resistant disease expressing high levels of the wild type androgen receptor and the TMPRSS2-ERG fusion transcript. Using next generation sequencing, we assembled the structural variations in VCaP genomic DNA and observed a massive number of genomic rearrangements along the q arm of chromosome 5, characteristic of chromothripsis. Chromothripsis is a recently recognized phenomenon characterized by extensive chromosomal shattering in a single catastrophic event, mainly detected in cancer cells. Various structural events identified on chromosome 5q of VCaP resulted in gene fusions. Out of the 18 gene fusion candidates tested, 15 were confirmed on genomic level. In our set of gene fusions, only rarely we observe microhomology flanking the breakpoints. On RNA level, only five transcripts were detected and NDUFAF2-MAST4 was the only resulting in an in-frame fusion transcript. Our data indicate that although a marker of genomic instability, chromothripsis might lead to only a limited number of functionally relevant fusion genes. NCBI 36/hg18 CPLX2,UBXD8;EBF1,FBXL17;EBF1,FEM1C;EFNA5,PCDHB7;JMY,DMGDH;KCNN2,EBF1;LMAN2,AP3S1;NDUFAF2,MAST4;PDE4D,C5orf47;PDE4D,FAM172A;PDE4D,PPP2R2B;PDE8B,UIMC1;PPP2R2B,FAM172A;RASGRF2,RNF145;TMPRSS2,ERG;TRIM40,FBXO38;YTHDC2,PPP2R2B;ZFP62,RGNEF CTDB0022 Research 23860044 Lusine Nazaryan, Eunice G Stefanou, Claus Hansen, Nadezda Kosyakova, Mads Bak, Freddie H Sharkey, Theodora Mantziou, Anastasios D Papanastasiou, Voula Velissariou, Thomas Liehr, Maria Syrrou, and Niels Tommerup The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2 Eur J Hum Genet 2013 Jul 2,5,7,16 Developmental delay Next Generation Sequencing Homo sapiens 23860044_1 Roche- Nimblegen 12x135K wholegenome array + Illumina Genome Analyzer IIx chr7:12814117-14251879:1;chr7:13505886-114129050:1 hs2:56842021-56843702,hs5:14939951-14942072;hs5:14937322-14939104,hs7:114129941-114130585;hs2:41655927-41657380,hs5:17605465-17606575;hs16:12911097-12911134,hs18:7850070-7850105;hs5:150566906-150566941,hs14:59017557-59017594;hs2:41654255-41655319,hs2:60301348-60302967;hs5:12445869-12447205,hs5:24398254-24399503;hs5:15076731-15078724,hs5:22227821-22229757;hs2:56844026-56845886,hs2:60304057-60305174;hs5:12444115-12445044,hs5:15074553-15076007;hs7:12810996-12811974,hs7:13503520-13504608;hs2:161019051-161022248,hs2:164128044-164131466 CDH12;DGKB;FOXP2 Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. However, only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could we delineate the precise structure of the derivative chromosomes. GRCh37/hg19 No NA CTDB0041 Research 23991058 Valentina Boeva, Stephanie Jouannet, Romain Daveau, Valerie Combaret, Cecile Pierre-Eugene, Alex Cazes, Caroline Louis-Brennetot, Gudrun Schleiermacher, Sandrine Ferrand, Gaelle Pierron, Alban Lermine, Thomas Rio Frio, Virginie Raynal, Gilles Vassal, Emma Breakpoint Features of Genomic Rearrangements in Neuroblastoma with Unbalanced Translocations and Chromothripsis PLoS One 2013 Aug 2,3 Neuroblastoma Next Generation Sequencing Homo sapiens CLB-Re Illumina Genome Analyzer Iix + SOLiD V4/5500 chr10:105458121-105464131:-1;chr10:105723280-105737556:-1;chr10:24942178-24948838:-1;chr10:29709684-29715523:-1;chr10:45155220-45161771:-1;chr10:53469515-53476392:-1;chr10:54013499-54021406:-1;chr10:5509847-5521886:-1;chr10:64705114-64710201:-1;chr10:65506075-65514595:-1;chr11:10257824-10264178:-1;chr11:113529905-113545953:-1;chr11:130223206-130233552:-1;chr11:24627305-24768846:-1;chr11:25560956-25567755:-1;chr11:25604815-25631706:-1;chr11:31390641-31400907:-1;chr11:55780728-55789968:-1;chr11:60848734-60856340:-1;chr11:7131991-7139274:-1;chr12:1025663-1032616:-1;chr12:102833102-102841446:-1;chr12:105677603-105684530:-1;chr12:126780604-126792551:-1;chr12:126786844-126805742:-1;chr12:132062023-132067915:-1;chr12:1435294-1441841:-1;chr12:18720743-18727832:-1;chr12:28092509-28100965:-1;chr12:29841786-29849559:-1;chr12:74364859-74379696:-1;chr12:86424120-86436366:-1;chr13:24810564-24816480:-1;chr13:65348987-65356665:-1;chr13:83163270-83175249:-1;chr13:90860112-90867745:-1;chr14:30837800-30857770:-1;chr14:31033049-31043342:-1;chr14:70014035-70025613:-1;chr14:83432196-83439242:-1;chr14:85136095-85142294:-1;chr15:100413465-100425713:-1;chr15:39039098-39058721:-1;chr15:40819382-40826641:-1;chr15:54197026-54205944:-1;chr15:62130354-62765116:1;chr15:67402307-67408739:-1;chr15:71471579-71480909:-1;chr15:92673464-92680008:-1;chr16:13291703-13299257:-1;chr16:46893200-46904565:-1;chr16:57363619-57369724:-1;chr16:69464955-69478078:-1;chr16:89018234-89024674:-1;chr16:89147348-89152830:-1;chr17:1210174-1217327:-1;chr17:12619669-12627223:-1;chr17:41909446-41921444:-1;chr17:48424192-48430182:-1;chr17:48870524-48887434:-1;chr17:49620560-49629892:-1;chr17:57121377-57134048:-1;chr17:65431353-65702059:1;chr17:79285394-79352771:1;chr18:22889412-22896120:-1;chr18:37808749-37815358:-1;chr18:46964186-46970605:-1;chr18:47995190-48002820:-1;chr18:4810726-4817614:-1;chr18:49213979-49230237:-1;chr18:57451084-57459047:-1;chr18:67207145-67220815:-1;chr18:68843786-68850876:-1;chr18:74294471-74300856:-1;chr18:77054662-77062050:-1;chr19:10822851-10839405:-1;chr19:11466215-11481125:-1;chr19:19746599-19762597:-1;chr19:29166628-29179071:-1;chr19:37528181-37538930:-1;chr19:4615558-4622411:-1;chr19:8816349-8830388:-1;chr1:10450349-10460635:-1;chr1:150357425-150363998:-1;chr1:152758022-152773660:-1;chr1:187293972-187304422:-1;chr1:20495958-20500886:-1;chr1:205234411-205251644:-1;chr1:20929404-20935698:-1;chr1:209619370-209630317:-1;chr1:22200590-22209496:-1;chr1:22355818-22365883:-1;chr1:24955919-24972856:-1;chr1:28548906-28556599:-1;chr1:30735555-30742966:-1;chr1:39081097-39087826:-1;chr1:75329730-75338768:-1;chr1:9762183-9775792:-1;chr20:24386079-24392002:-1;chr20:42522897-42542087:-1;chr20:50648936-50657822:-1;chr20:5430490-5437212:-1;chr20:60543779-60548947:-1;chr20:7602509-7610411:-1;chr21:18099736-18106212:-1;chr21:19892318-19952705:-1;chr21:36069697-36076185:-1;chr21:45827507-45833716:-1;chr22:36610426-36617446:-1;chr22:49382832-49396194:-1;chr2:10034150-18916038:1;chr2:107923218-107928076:-1;chr2:1093350-39259159:-1;chr2:113413521-113433115:-1;chr2:11708510-23148143:-1;chr2:118033649-118045033:-1;chr2:126366733-126373216:-1;chr2:12851378-37913001:1;chr2:12855133-21201704:-1;chr2:132531297-132536832:-1;chr2:135278552-135285771:-1;chr2:13924948-43205226:-1;chr2:154892914-154901512:-1;chr2:15822934-16460194:1;chr2:15847288-15998209:-1;chr2:15897929-16364768:-1;chr2:15907966-15938573:-1;chr2:15949556-16227028:-1;chr2:15976358-16045752:1;chr2:15976647-16025251:1;chr2:15996881-16451508:1;chr2:16004290-16268180:-1;chr2:16004913-16332415:-1;chr2:16081455-16424933:-1;chr2:160852650-160859146:-1;chr2:16187730-16267065:1;chr2:16194730-16212391:-1;chr2:16211558-16408349:1;chr2:173177212-173189060:-1;chr2:175115585-175128133:-1;chr2:1760878-19052052:1;chr2:182842513-182857861:-1;chr2:183493013-184099332:-1;chr2:18780480-39379203:-1;chr2:18801998-23528365:1;chr2:19000380-19006785:-1;chr2:19949321-43257742:-1;chr2:19955896-30326069:1;chr2:20817719-30355624:-1;chr2:21455352-33172052:1;chr2:216204225-216218114:-1;chr2:21678160-42227848:1;chr2:225290248-225296907:-1;chr2:2288292-38563375:-1;chr2:23145457-31746023:-1;chr2:23391003-39059066:-1;chr2:234473440-234478961:-1;chr2:23534404-37037624:1;chr2:238550840-238562264:-1;chr2:23863094-34468960:-1;chr2:239987772-239993987:-1;chr2:24032752-38061822:1;chr2:24202767-40081098:-1;chr2:24259681-32547024:-1;chr2:24287458-25160824:1;chr2:25013692-40473754:1;chr2:25347050-42971111:-1;chr2:26155286-26597203:-1;chr2:26370277-39048305:1;chr2:27171754-43580748:1;chr2:27419636-42106481:-1;chr2:28220205-30346273:1;chr2:28891317-36011905:-1;chr2:29254836-39613817:1;chr2:2926879-35703077:1;chr2:29727956-29740502:-1;chr2:29790720-37043309:-1;chr2:31001400-43152413:1;chr2:32118224-39011124:-1;chr2:32572467-42770824:-1;chr2:3294938-24790708:1;chr2:33221519-33230299:-1;chr2:33451530-42314228:1;chr2:34693372-34738659:-1;chr2:34733067-34750213:-1;chr2:36362070-36692846:1;chr2:36652366-36690450:1;chr2:38733128-42962902:1;chr2:39365345-43014298:1;chr2:3975228-31899912:1;chr2:41236855-41253460:-1;chr2:42844555-42968590:-1;chr2:43652893-43659928:-1;chr2:4483508-33617072:-1;chr2:4989937-10830972:1;chr2:585954-34043156:1;chr2:674395-15119647:-1;chr2:70189045-70202428:-1;chr2:7348550-19056544:-1;chr2:76016601-76036004:-1;chr2:77522512-77537300:-1;chr2:78320733-78331279:-1;chr2:8113106-16936056:-1;chr2:8114318-12306404:1;chr2:8628714-21880137:1;chr2:9163294-31904146:-1;chr2:9172957-42358530:1;chr3:107327170-107334876:-1;chr3:137069308-137076000:-1;chr3:182133954-182152632:-1;chr3:18753010-18758187:-1;chr3:192301989-192315730:-1;chr3:192387430-192394798:-1;chr3:194552495-194559298:-1;chr3:20308641-20320796:-1;chr3:2492772-2499243:-1;chr3:58822363-64635286:-1;chr3:58884645-75615580:1;chr3:59772523-78992768:1;chr3:60426623-60446574:-1;chr3:64016169-64673306:1;chr3:64146880-65729422:1;chr3:65668779-74648067:1;chr3:68358494-77013690:-1;chr3:68509083-73801788:1;chr3:69653134-69669786:-1;chr3:76465839-76485092:-1;chr3:84697244-84705989:-1;chr4:104796736-104814062:-1;chr4:108507845-108517376:-1;chr4:113577029-113589718:-1;chr4:138962879-138970126:-1;chr4:146616825-146627290:-1;chr4:148215754-148232005:-1;chr4:150157720-150164183:-1;chr4:159002405-159020686:-1;chr4:159796862-159804270:-1;chr4:162446226-162454836:-1;chr4:171299806-171313417:-1;chr4:177383920-184910806:-1;chr4:183750366-183757906:-1;chr4:184653978-184660945:-1;chr4:185378396-185657522:1;chr4:186975331-186981450:-1;chr4:187029101-187048849:-1;chr4:60549116-60579876:1;chr4:60703948-60941727:1;chr4:62082448-62090380:-1;chr4:78056639-78075060:-1;chr4:79041004-79052653:-1;chr4:80358101-80365823:-1;chr5:108864505-108874017:-1;chr5:117378442-117385059:-1;chr5:119035802-119044702:-1;chr5:126078590-126086510:-1;chr5:132916247-132927734:-1;chr5:139090250-139200290:1;chr5:143928619-143937655:-1;chr5:151512181-151522033:-1;chr5:16921132-16933098:-1;chr5:176384862-176393270:-1;chr5:179367037-179378526:-1;chr5:30912783-30919280:-1;chr5:42626937-42633515:-1;chr5:57774624-57780912:-1;chr5:60857251-61052299:1;chr5:65024932-65033014:-1;chr5:65265717-65273284:-1;chr5:75053076-75068863:-1;chr5:80683157-80689104:-1;chr5:81562941-81572309:-1;chr6:141545963-141552225:-1;chr6:151384468-151401463:-1;chr6:161000141-161007291:-1;chr6:1666602-1678955:-1;chr6:23524647-23539457:-1;chr6:40362594-40372223:-1;chr6:56755451-56763807:-1;chr6:69139384-69145564:-1;chr6:7090783-7098872:-1;chr6:72523269-72538633:-1;chr6:73219019-73225495:-1;chr6:84089162-84098267:-1;chr6:86023164-86028765:-1;chr6:95190206-95197331:-1;chr7:107461033-107467909:-1;chr7:113151793-113166648:-1;chr7:119351329-119473895:-1;chr7:121580747-121595207:-1;chr7:130743909-130759438:-1;chr7:148061369-148066088:-1;chr7:150392163-150399605:-1;chr7:151227404-151234299:-1;chr7:153763616-153946452:1;chr7:26134090-26147984:-1;chr7:31521579-31528191:-1;chr7:38505238-38516946:-1;chr7:4155423-4163074:-1;chr7:46110874-46118490:-1;chr7:52799854-52813661:-1;chr7:7580747-7587875:-1;chr7:79502448-79517767:-1;chr7:83694280-83712993:-1;chr7:87617991-87626846:-1;chr8:11225409-11231832:-1;chr8:114054172-114061438:-1;chr8:115078302-115083347:-1;chr8:120151395-120163948:-1;chr8:127189033-127197607:-1;chr8:131847619-131855484:-1;chr8:15282842-15295655:-1;chr8:16199163-16210113:-1;chr8:1834063-1840937:-1;chr8:76377499-76383904:-1;chr8:8282925-8293798:-1;chr9:103525092-103544692:-1;chr9:104216877-104222734:-1;chr9:123254379-123262592:-1;chr9:125684895-125700821:-1;chr9:130178668-130188950:-1;chr9:130842616-130853014:-1;chr9:132921076-132930375:-1;chr9:139996298-140017337:1;chr9:29090397-29099781:-1;chr9:29258348-29275562:-1;chr9:72101829-72109353:-1;chr9:73035538-73046381:-1;chr9:74802074-74818113:-1;chr9:77960552-77971260:-1;chrX:74899525-74914959:-1;chrX:81981139-81991007:-1;chrY:22541163-22546799:-1 hs1:55966057-55968218,hs17:81103377-81105679;hs1:223883823-223886244,hs7:126064537-126067125;hs1:223986682-223988946,hs7:126005149-126007421;hs2:486445-487871,hs3:59820161-59821840;hs2:606085-608411,hs3:63899068-63901112;hs2:957722-960230,hs3:64089643-64091938;hs2:964544-967193,hs3:76517860-76520172;hs2:2197174-2199055,hs3:60006616-60008685;hs2:2278011-2280106,hs3:59591487-59593404;hs2:2649790-2652659,hs3:65183050-65185549;hs2:2704986-2708076,hs3:69226494-69229215;hs2:2768789-2771402,hs3:75600747-75603475;hs2:2839621-2841699,hs3:72594846-72597052;hs2:2847991-2850768,hs3:60901762-60904827;hs2:3257423-3260765,hs3:67272579-67275725;hs2:3290095-3292953,hs3:77802901-77805974;hs2:3351183-3353596,hs3:59236917-59239457;hs2:3433953-3436632,hs3:63862782-63865215;hs2:3680814-3683112,hs3:76585187-76587503;hs2:4646621-4648635,hs3:73888496-73890705;hs2:6535820-6538430,hs3:69804187-69806818;hs2:7264629-7267603,hs3:63611482-63614320;hs2:7401984-7403351,hs3:69705577-69707408;hs2:9345306-9348356,hs3:65389257-65390768;hs2:10153000-10155339,hs3:74300858-74303546;hs2:10162897-10165789,hs3:76344663-76347565;hs2:11212468-11215100,hs3:60255763-60258796;hs2:11691390-11694136,hs3:74653417-74655752;hs2:13813541-13816146,hs3:66581249-66583483;hs2:14115772-14118579,hs3:69989775-69992494;hs2:14772885-14775849,hs3:60000360-60003269;hs2:15189041-15191794,hs3:59851626-59854168;hs2:15548795-15551143,hs3:65732754-65734748;hs2:15684792-15687331,hs3:59726000-59728901;hs2:16058677-16061511,hs3:65558675-65561352;hs2:16125417-16127850,hs3:69135121-69137521;hs2:16513681-16515804,hs3:66553845-66556237;hs2:17345934-17348521,hs3:59487857-59490072;hs2:18288341-18291407,hs3:73021750-73024500;hs2:19548608-19551297,hs3:59445449-59448282;hs2:20790540-20793082,hs3:77783725-77786478;hs2:21465376-21467486,hs3:59483830-59485948;hs2:22984940-22986929,hs3:63747794-63749666;hs2:23738297-23740489,hs3:77215896-77218165;hs2:24111879-24113665,hs3:69912436-69914109;hs2:25907279-25910337,hs3:65318021-65320358;hs2:26250118-26252143,hs3:61930846-61932945;hs2:26327961-26330511,hs3:58727613-58729823;hs2:26333510-26335241,hs3:64504406-64506376;hs2:26548319-26550042,hs3:69132982-69134750;hs2:26667839-26670783,hs3:76235686-76238835;hs2:26695079-26697722,hs3:75377691-75380138;hs2:27187355-27189497,hs19:42743153-42745528;hs2:27665209-27666226,hs3:71453763-71455133;hs2:28464933-28467807,hs3:65700015-65702813;hs2:28646027-28648711,hs3:72146218-72149274;hs2:29095517-29098468,hs3:66696588-66699578;hs2:29492561-29494889,hs3:61202830-61205686;hs2:29570213-29572635,hs3:65183191-65185750;hs2:29704659-29707035,hs3:74522714-74525270;hs2:29757959-29759731,hs3:63685853-63687508;hs2:30189224-30191694,hs3:73628572-73630938;hs2:33180673-33183308,hs3:69983213-69985691;hs2:33828651-33830849,hs3:77109229-77110946;hs2:34172898-34175825,hs3:59437354-59440266;hs2:35003297-35005537,hs3:64096746-64099101;hs2:35048714-35051665,hs3:60003021-60005869;hs2:35197552-35199069,hs3:69054283-69055437;hs2:36462232-36465260,hs3:75077897-75080929;hs2:36586319-36588758,hs3:60969660-60971895;hs2:37814034-37815917,hs3:64589128-64591457;hs2:38088577-38091085,hs3:73498048-73500690;hs2:38868907-38870606,hs3:76349897-76351702;hs2:39251170-39253170,hs3:59421928-59423719;hs2:39359575-39361968,hs3:59100508-59102768;hs2:40487140-40490077,hs3:74425937-74429196;hs2:40602840-40604321,hs3:65956482-65958445;hs2:40974111-40976388,hs3:64522322-64524554;hs2:41514683-41516444,hs3:59505157-59507008;hs2:42283303-42285598,hs3:67275059-67277483;hs2:42734344-42735623,hs3:59925262-59926700;hs2:42742863-42744417,hs3:66989612-66991577;hs2:43168177-43169941,hs3:67344169-67345880;hs2:43309319-43311605,hs3:66139399-66141438;hs2:43525981-43527468,hs3:63761368-63763207;hs2:43639870-43642070,hs3:60907713-60909583;hs2:43803569-43806538,hs3:62824116-62827097;hs2:43808427-43810620,hs3:76179358-76181879;hs2:43964036-43966750,hs3:58587126-58589851;hs2:67067365-67069477,hs5:1321130-1323418;hs4:60575252-60577773,hs19:14946000-14948449;hs6:26553121-26555461,hs11:134943989-134945996;hs8:26635858-26638740,hs10:34230363-34233579;hs11:78541734-78544314,hs14:104177979-104180310;hs17:37803564-37805532,hs19:4790411-4792511;hs1:2036754-2038195,hs1:2038951-2040408;hs1:5218640-5219963,hs1:5220717-5222100;hs1:11029926-11031142,hs1:11031210-11032248;hs1:25854127-25855916,hs1:25856045-25857950;hs1:55466766-55468680,hs1:55468924-55470743;hs1:60104121-60106230,hs1:60107346-60110410;hs1:64670979-64673633,hs1:64701317-64704176;hs1:83123332-83125951,hs1:83127820-83130360;hs1:111800532-111802314,hs1:111802587-111804339;hs1:179649516-179650980,hs1:179651453-179653157;hs2:485268-487953,hs2:6812035-6815175;hs2:496193-497583,hs2:15290746-15292091;hs2:521805-524490,hs2:2333220-2336050;hs2:921203-923561,hs2:42177811-42180352;hs2:1308481-1310849,hs2:41614104-41616350;hs2:1525992-1528114,hs2:43545064-43547492;hs2:1796112-1799072,hs2:3101701-3104276;hs2:1879146-1881427,hs2:38074643-38077316;hs2:1993703-1995551,hs2:3888475-3890073;hs2:2145924-2148600,hs2:19653347-19656128;hs2:2263844-2264782,hs2:16246659-16247526;hs2:2657702-2660536,hs2:10949807-10953102;hs2:2699211-2701752,hs2:22620322-22623186;hs2:3693857-3696067,hs2:25623938-25626490;hs2:4498628-4499672,hs2:4500808-4501782;hs2:4646751-4648965,hs2:4649000-4651049;hs2:4902090-4904385,hs2:24606040-24608429;hs2:5827467-5830076,hs2:39718013-39720646;hs2:8127440-8129885,hs2:20735495-20737860;hs2:8671381-8672763,hs2:26366876-26368225;hs2:8988767-8991506,hs2:38643697-38646632;hs2:9405927-9408698,hs2:10684591-10686869;hs2:9441222-9443883,hs2:11518433-11521450;hs2:9915195-9916988,hs2:9917202-9919050;hs2:10044223-10047098,hs2:42362628-42365449;hs2:10156964-10159930,hs2:39146984-39150139;hs2:10409324-10411709,hs2:37310719-37313176;hs2:10468498-10470862,hs2:31713650-31716004;hs2:10496360-10497780,hs2:29234110-29235879;hs2:10653755-10656323,hs2:23608471-23611303;hs2:11251846-11253712,hs2:11253903-11255223;hs2:11633283-11634771,hs2:30025446-30026740;hs2:11682445-11683987,hs2:24028991-24030520;hs2:11756192-11758174,hs2:11758330-11760289;hs2:12189881-12192828,hs2:43893764-43896073;hs2:12546328-12549608,hs2:30439346-30442678;hs2:14116089-14118630,hs2:17921605-17924152;hs2:14886758-14889439,hs2:33628719-33631540;hs2:15542668-15545160,hs2:28647561-28650414;hs2:15695413-15698424,hs2:42063959-42066869;hs2:15838413-15840618,hs2:15891624-15893866;hs2:15864700-15868063,hs2:16223162-16226138;hs2:15868128-15871005,hs2:15891803-15894278;hs2:15952313-15955099,hs2:16052630-16055433;hs2:15973167-15975399,hs2:16140544-16142862;hs2:15979169-15981351,hs2:16208457-16210573;hs2:15991745-15994940,hs2:16349524-16352453;hs2:16002009-16004688,hs2:16037263-16040143;hs2:16008026-16010674,hs2:16138806-16141026;hs2:16059663-16061464,hs2:16107178-16108439;hs2:16062319-16065364,hs2:16417194-16420310;hs2:16077514-16079560,hs2:16249092-16250883;hs2:16084491-16087179,hs2:16166370-16168703;hs2:16160331-16163543,hs2:16420706-16423833;hs2:16179460-16181785,hs2:16359008-16361051;hs2:16183878-16186429,hs2:16391463-16394220;hs2:16253585-16254877,hs2:16378947-16380619;hs2:17468334-17470453,hs2:18189914-18191938;hs2:17516253-17518625,hs2:42801544-42803761;hs2:18837219-18839841,hs2:33539836-33542320;hs2:20643150-20645875,hs2:25483139-25485789;hs2:21143836-21146558,hs2:35477826-35480355;hs2:22045493-22046252,hs2:22046553-22047342;hs2:22232654-22234118,hs2:27515388-27516741;hs2:22786752-22788801,hs2:24238727-24240874;hs2:23150056-23152413,hs2:37563294-37565969;hs2:23264924-23265939,hs2:42276128-42277214;hs2:23290508-23291540,hs2:30375175-30376386;hs2:23705388-23708433,hs2:42231165-42234315;hs2:24021752-24024647,hs2:42749006-42751380;hs2:24575935-24578496,hs2:33607721-33610251;hs2:24649861-24652469,hs2:42515770-42518243;hs2:24909325-24911993,hs2:25428825-25431405;hs2:25901155-25903876,hs2:32227547-32230056;hs2:26274217-26276568,hs2:28803091-28805073;hs2:26402699-26405612,hs2:39346133-39349110;hs2:26823270-26825932,hs2:29754187-29756689;hs2:26927940-26930161,hs2:29524619-29526999;hs2:27510710-27513167,hs2:32958525-32961111;hs2:27984034-27986595,hs2:29905651-29908574;hs2:28811168-28813802,hs2:33296358-33298772;hs2:29487806-29490828,hs2:33302728-33305113;hs2:29747307-29750326,hs2:42156154-42158826;hs2:30052989-30054071,hs2:30055109-30056137;hs2:30414481-30416783,hs2:42098158-42100927;hs2:32578441-32581028,hs2:36812170-36814944;hs2:39152842-39155113,hs2:43494403-43496871;hs2:42070462-42073380,hs2:43550303-43553381;hs2:42140522-42143126,hs2:43251318-43254099;hs2:68132675-68133721,hs2:68134077-68135578;hs2:98812030-98815210,hs2:98826633-98829326;hs2:105601391-105603916,hs2:105708147-105710881;hs2:137153636-137157039,hs2:137154627-137157906;hs2:217086882-217089925,hs2:217092520-217095748;hs3:1678600-1679998,hs3:1680061-1682135;hs3:3230723-3232311,hs3:3232463-3234045;hs3:21778264-21781083,hs3:21782654-21785131;hs3:26448454-26450720,hs3:26452334-26454212;hs3:38123908-38126081,hs3:38126135-38128321;hs3:39213933-39216030,hs3:39216048-39218277;hs3:58733519-58736230,hs3:64343216-64345848;hs3:59586547-59589243,hs3:64123601-64126295;hs3:59616141-59618134,hs3:64115578-64117324;hs3:60535269-60536918,hs3:60537318-60538805;hs3:66566962-66569090,hs3:69136415-69138230;hs3:66589708-66592665,hs3:69613992-69616833;hs3:67266961-67269364,hs3:76871792-76874505;hs3:67280907-67283686,hs3:68365167-68368267;hs3:69036723-69039481,hs3:73100386-73103348;hs3:84591599-84592420,hs3:84593506-84594439;hs3:101355168-101357535,hs3:101360029-101362863;hs3:103467293-103468197,hs3:103468860-103470036;hs3:126089043-126089906,hs3:126089852-126091469;hs3:137311559-137314419,hs3:137316539-137319507;hs3:140541408-140544203,hs3:140547156-140549873;hs3:167716952-167718548,hs3:167718751-167720553;hs3:178565061-178567325,hs3:178568369-178570477;hs3:193991687-193993353,hs3:193993547-193995585;hs4:3814866-3816768,hs4:3817049-3818644;hs4:5666268-5667492,hs4:5668227-5669699;hs4:62281919-62283982,hs4:62285381-62288054;hs4:77346896-77347856,hs4:77348924-77350086;hs4:80273645-80274932,hs4:80273734-80276586;hs4:138176102-138177283,hs4:138177681-138179024;hs5:1538110-1540035,hs5:1540050-1541839;hs5:6447371-6448736,hs5:6448937-6450310;hs5:7935445-7936763,hs5:7937361-7938968;hs5:43539348-43541237,hs5:43541474-43543020;hs5:62499634-62500756,hs5:62501885-62502833;hs5:96656259-96658721,hs5:96843168-96845125;hs5:103924846-103926998,hs5:103926809-103928587;hs5:118199057-118199756,hs5:118199790-118200579;hs5:121572790-121576026,hs5:121580887-121583604;hs5:168151362-168153003,hs5:168153558-168155037;hs5:174476210-174477308,hs5:174478310-174479342;hs5:179020219-179021402,hs5:179021773-179023210;hs5:179560203-179561470,hs5:179560744-179563455;hs6:1925454-1927320,hs6:1927502-1929211;hs6:3775317-3776452,hs6:3777454-3778411;hs6:24925295-24927478,hs6:24927417-24929518;hs6:26571737-26574397,hs6:26594023-26596699;hs6:35135364-35137432,hs6:35137315-35139290;hs6:35679585-35680811,hs6:35680856-35682875;hs6:46309619-46310270,hs6:46310375-46311293;hs6:70276058-70277077,hs6:70277225-70278980;hs6:149799619-149800808,hs6:149800730-149804617;hs6:160876242-160877800,hs6:160877993-160879653;hs6:166827364-166828293,hs6:166828241-166830402;hs7:8190952-8191878,hs7:8193082-8194068;hs7:16169446-16171657,hs7:16174097-16177005;hs7:22879091-22880690,hs7:22881333-22882924;hs7:97870393-97871554,hs7:97872518-97873737;hs7:106410905-106411877,hs7:106412625-106413706;hs7:131756426-131758257,hs7:131758433-131760420;hs7:158106036-158107544,hs7:158107700-158109483;hs8:1112375-1114019,hs8:1114231-1116092;hs8:2030538-2034285,hs8:2034154-2035333;hs8:14379596-14381973,hs8:14383988-14387183;hs8:19317117-19319139,hs8:19319197-19321262;hs8:27774427-27776498,hs8:27776562-27778544;hs8:37500855-37502856,hs8:37503027-37504944;hs8:41756004-41758131,hs8:41758218-41760313;hs8:70070596-70074137,hs8:70072820-70074477;hs8:85872691-85874254,hs8:85874508-85876353;hs8:102696180-102696791,hs8:102697856-102698412;hs8:133918717-133920596,hs8:133920682-133921947;hs8:143511602-143513577,hs8:143513584-143515116;hs8:145060957-145063148,hs8:145063174-145064637;hs8:145286299-145288105,hs8:145288288-145289750;hs9:20972728-20973691,hs9:20974836-20975559;hs9:36762423-36764137,hs9:36764458-36766127;hs9:95968995-95970072,hs9:95971109-95971647;hs9:101356144-101357802,hs9:101358039-101359388;hs9:104566519-104569464,hs9:104570502-104573187;hs9:135686394-135688205,hs9:135688137-135689697;hs9:136248258-136249029,hs9:136249601-136250470;hs9:139525115-139526749,hs9:139527253-139528409;hs9:139927303-139928681,hs9:139929517-139930871;hs10:2433553-2434524,hs10:2434876-2436596;hs10:3301256-3301805,hs10:3302358-3302872;hs10:5617550-5618802,hs10:5619747-5620973;hs10:28936697-28938489,hs10:28938926-28940660;hs10:31974182-31975929,hs10:31976089-31978066;hs10:35898920-35899750,hs10:35900285-35900872;hs10:35953990-35956044,hs10:35956068-35957406;hs10:44684726-44687060,hs10:44687966-44691189;hs10:98173405-98174077,hs10:98173646-98176127;hs10:103613447-103614851,hs10:103614904-103616597;hs10:105794132-105795983,hs10:105796206-105798208;hs10:129511663-129512698,hs10:129513454-129514012;hs11:36074884-36076593,hs11:36076844-36078617;hs11:44570773-44572185,hs11:44572914-44574379;hs11:47391903-47392843,hs11:47392969-47394296;hs11:48991108-48993214,hs11:48993347-48995326;hs11:67703296-67704257,hs11:67705024-67705911;hs11:72960795-72962599,hs11:72962961-72964754;hs11:89682170-89684240,hs11:89690557-89692893;hs11:119517858-119519038,hs11:119519107-119521153;hs11:120136641-120137868,hs11:120138801-120139991;hs11:131993973-131995112,hs11:131995639-131997036;hs11:133222890-133223858,hs11:133224685-133225818;hs11:133700860-133702537,hs11:133703088-133704777;hs12:1229577-1231827,hs12:1231829-1232859;hs12:1681804-1683553,hs12:1683578-1685634;hs12:5588822-5590516,hs12:5590934-5592670;hs12:7000763-7002119,hs12:7002630-7004004;hs12:12932419-12933682,hs12:12933723-12934865;hs12:15197628-15199196,hs12:15199299-15201195;hs12:57584301-57585440,hs12:57586445-57587537;hs12:69252974-69255388,hs12:69256522-69258626;hs12:110097579-110099359,hs12:110099540-110101443;hs12:111316708-111318526,hs12:111318705-111320729;hs12:116235635-116237524,hs12:116237744-116239769;hs12:121489035-121490522,hs12:121491079-121492626;hs12:123385163-123386963,hs12:123386993-123388699;hs12:130862858-130864704,hs12:130864762-130866782;hs13:104294284-104295937,hs13:104296222-104298092;hs13:113828707-113830809,hs13:113830955-113832993;hs14:44885321-44886262,hs14:44887499-44888426;hs14:69332010-69332805,hs14:69332955-69333806;hs14:82114234-82115623,hs14:82116091-82117726;hs14:89175882-89177434,hs14:89177757-89179009;hs14:91757870-91759867,hs14:91759673-91761770;hs14:104696086-104697521,hs14:104698223-104699701;hs15:24870528-24871706,hs15:24871991-24873094;hs15:83549271-83551604,hs15:83557766-83560863;hs15:86555379-86556196,hs15:86556795-86557776;hs15:100929609-100931043,hs15:100931144-100932873;hs16:1162006-1164002,hs16:1163889-1165723;hs16:7946405-7948049,hs16:7948531-7949918;hs16:17164055-17165395,hs16:17166147-17167414;hs16:23786033-23787159,hs16:23787566-23788798;hs16:25637039-25639246,hs16:25640514-25643097;hs16:81736380-81737720,hs16:81738540-81739893;hs16:87770826-87772689,hs16:87772753-87774513;hs16:89110497-89112426,hs16:89112745-89114619;hs17:10748237-10750223,hs17:10750474-10752100;hs17:17361260-17363389,hs17:17363433-17365242;hs17:36273855-36277042,hs17:36292439-36295211;hs18:14358560-14360259,hs18:14360550-14362402;hs18:24569704-24571516,hs18:24572489-24575088;hs18:34862653-34863696,hs18:34864877-34865922;hs18:35358933-35360275,hs18:35361051-35362062;hs18:55874379-55876217,hs18:55876508-55878332;hs18:58670609-58671983,hs18:58672967-58675606;hs18:60883878-60885965,hs18:60885852-60887978;hs18:74677516-74679562,hs18:74679724-74681322;hs19:14948988-14951799,hs19:14951908-14954434;hs19:33948548-33949758,hs19:33950470-33951857;hs19:42774948-42777136,hs19:42783478-42785519;hs19:57452342-57453361,hs19:57454298-57455337;hs20:24508928-24510705,hs20:24511030-24512937;hs20:30909471-30910688,hs20:30911281-30912521;hs20:31149113-31150902,hs20:31151152-31153019;hs20:36750745-36751722,hs20:36752987-36753943;hs20:36982577-36984543,hs20:36984572-36986688;hs20:38083723-38086575,hs20:38108258-38110982;hs20:42268741-42271857,hs20:42274696-42277338;hs20:51819220-51820463,hs20:51821422-51822596;hs21:18662734-18664468,hs21:18664612-18666655;hs21:39430214-39431963,hs21:39432136-39433942;hs21:43347296-43350072,hs21:43353577-43356312;hs21:43895273-43896989,hs21:43897144-43899197;hs22:23475510-23478215,hs22:23479675-23482121;hs22:46864727-46865782,hs22:46865869-46866569;hsX:117451678-117454032,hsX:117455089-117457048;hsX:136091199-136092964,hsX:136093039-136094957;hsX:147660963-147662170,hsX:147663153-147664307 ACOT12;ADAM22;ADAMTS9;ADAMTS9-AS2;ADCY8;ADRA1A;AFF2;AK8;ALK;AMPH;ANK1;APBA1;APOLD1;ARHGAP21;ARHGEF10;ARHGEF33;ARL6IP5;ASAP2;ASPRV1;ATAD2B;ATIC;ATL2;ATP13A1;ATP9B;ATXN7;BBX;BCL2;BRE;BSND;C10orf76;C1orf127;C2CD2;C2orf44;C3orf64;C3orf67;C4orf51;C8orf12;C9orf139;C9orf96;CADPS;CAPN13;CBFA2T3;CCDC164;CCDC63;CCDC75;CCDC88C;CDA;CDK5RAP2;CELF4;CELSR1;CHST9;CIB4;CLIC6;CLPTM1L;CMIP;CNTN3;CNTN4;CNTNAP2;COL17A1;COLEC11;CPM;CRIM1;CSGALNACT1;CSMD3;CYB5B;DCDC1;DHX57;DLEC1;DNAJC24;DNAJC8;DNM2;DNMT3A;DOK6;DPP6;DPYSL5;DSCR4;DTNB;DTWD2;DYM;EFR3B;EML4;EML5;EPT1;ERBB2IP;ERC1;EVC2;FAM179A;FAM19A1;FAM59B;FAM84A;FBXL14;FEZ2;FGF12;FGGY;FHIT;FKBP5;FLJ33534;FLJ43663;FNIP2;FOXP1;FRAS1;FRMD4B;FSTL4;FSTL5;G2E3;GABBR2;GALNT13;GDA;GHR;GMDS;GMIP;GPR113;GREB1;GRINA;GSK3A;GXYLT2;HAAO;HDAC4;HEATR7A;HOMER2;HPCAL1;HS1BP3;HSPG2;ICA1;IFT52;IGF1;IRF2;ISPD;ITSN2;KCNK3;KIAA1797;KIF3B;KIF3C;KLHDC4;KLHL29;KRTCAP3;LARP7;LBP;LCE1E;LDLRAD3;LINC00339;LOC100128590;LOC100271832;LOC339788;LOC387647;LOC388942;LOC400950;LOC440970;LOC641365;LOC649133;LOC728730;LPA;LPPR2;LRFN2;LRP1;LRRFIP1;LRRTM4;LTBP1;LUZP2;MAGI1;MAN1B1;MAP4K3;ME1;MEMO1;MFSD2B;MGAT4C;MIR4757;MITF;MLF1IP;MPP3;MRPL42P5;MRPS9;MTA3;MTHFD1L;MYCN;MYCNOS;MYO10;MYOCD;MYOM2;MYT1L;NBAS;NCOA1;NEDD4L;NLN;NOL10;NTF3;NTM;ODZ4;OPCML;OR7A10;OTOF;PAIP1;PARP10;PCBP1-AS1;PDIA6;PDZRN3;PEPD;PGD;PIK3C2G;PIK3CD;PITPNC1;PKDCC;PLA2G2C;PLA2R1;PLB1;PLEKHH2;POU2F3;PPP1R1C;PPP4R2;PRICKLE2;PRKCZ;PRKG1;PSD2;PTPRG;PTPRN2;PTPRZ1;PTRHD1;PVRL1;QTRT1;RAB10;RAD52;RASGEF1C;RCAN2;ROBO1;ROBO2;RPRD2;RPS23;RPS6KA2;RSPH1;RTDR1;RUFY1;SBF2;SCARA5;SDK1;SEMA3A;SGCZ;SH3PXD2A;SHISA9;SLC20A1;SLC25A25;SLC25A26;SLC8A1;SLCO3A1;SLIT3;SLK;SMAD3;SMC6;SNTG2;SOS1;SPATA13;SPI1;SRRM1;STARD3;STOX2;SYNDIG1;TAF1B;TBC1D3;TDH;TDRD5;TECPR1;TG;THADA;THSD4;TLL2;TMCC2;TMEM105;TMEM163;TMEM18;TMTC1;TP53BP2;TPO;TRIB2;TRIM37;TRIM54;TRPM2;TSHZ2;TSSC1;TTC15;TTC27;UBE2QL1;UBE2U;UBXN2A;UIMC1;USP40;VIT;VWA3B;WNK2;XRCC3;XYLT2;YPEL5;ZBTB26;ZC3H12D;ZNF236;ZNF385D;ZNF521;ZNF79 Inserm, U900, Paris, France Neuroblastoma is a pediatric cancer of the peripheral nervous system in which structural chromosome aberrations are emblematic of aggressive tumors. In this study, we performed an in-depth analysis of somatic rearrangements in two neuroblastoma cell lines and two primary tumors using paired-end sequencing of mate-pair libraries and RNA-seq. The cell lines presented with typical genetic alterations of neuroblastoma and the two tumors belong to the group of neuroblastoma exhibiting a profile of chromothripsis. Inter and intra-chromosomal rearrangements were identified in the four samples, allowing in particular characterization of unbalanced translocations at high resolution. Using complementary experiments, we further characterized 51 rearrangements at the base pair resolution that revealed 59 DNA junctions. In a subset of cases, complex rearrangements were observed with templated insertion of fragments of nearby sequences. Although we did not identify known particular motifs in the local environment of the breakpoints, we documented frequent microhomologies at the junctions in both chromothripsis and non-chromothripsis associated breakpoints. RNA-seq experiments confirmed expression of several predicted chimeric genes and genes with disrupted exon structure including ALK, NBAS, FHIT, PTPRD and ODZ4. Our study therefore indicates that both non-homologous end joining-mediated repair and replicative processes may account for genomic rearrangements in neuroblastoma. RNA-seq analysis allows the identification of the subset of abnormal transcripts expressed from genomic rearrangements that may be involved in neuroblastoma oncogenesis. GRCh37/hg19 ERP001414;ERP001988 Yes ALK,CNTN3;ALK,LTBP1;ARHGEF33,THADA;ASAP2,MAGI1;ASPRV1,PCBP1-AS1;ATAD2B,MITF;BRE,MAGI1;C3orf64,PPP4R2;C3orf67,ADAMTS9;CIB4,ALK;CRIM1,FHIT;DPYSL5,THADA;FAM179A,MAP4K3;FAM59B,SOS1;FAM84A,FHIT;FHIT,ROBO1;GREB1,ATAD2B;HPCAL1,FAM179A;ITSN2,LTBP1;KCNK3,ALK;KIF3C,EPT1;KLHL29,ROBO2;KRTCAP3,FOXP1;LTBP1,MITF;MYT1L,ATL2;MYT1L,FHIT;NBAS,MAGI1;PLB1,LTBP1;PRICKLE2,MAGI1;PTRHD1,LOC100128590;RAB10,ADAMTS9;RAB10,PLB1;SLC8A1,CNTN3;SLC8A1,MAGI1;SNTG2,PRICKLE2;SNTG2,SOS1;THADA,CADPS;THADA,FHIT;TPO,THADA;TRIM54,TTC27;TTC15,ATXN7 CTDB0042 Research 23991058 Valentina Boeva, Stephanie Jouannet, Romain Daveau, Valerie Combaret, Cecile Pierre-Eugene, Alex Cazes, Caroline Louis-Brennetot, Gudrun Schleiermacher, Sandrine Ferrand, Gaelle Pierron, Alban Lermine, Thomas Rio Frio, Virginie Raynal, Gilles Vassal, Emma Breakpoint Features of Genomic Rearrangements in Neuroblastoma with Unbalanced Translocations and Chromothripsis PLoS One 2013 Aug 1,2 Neuroblastoma Next Generation Sequencing Homo sapiens NB1141 Illumina Genome Analyzer Iix + SOLiD V4/5500 chr10:15529190-15534526:-1;chr10:82748693-82755344:-1;chr10:83881117-83891684:-1;chr11:11820549-11826177:-1;chr11:21844990-21851266:-1;chr11:80897522-80954853:-1;chr12:117084488-117091290:-1;chr12:59934068-59949389:-1;chr12:80154933-80162240:1;chr14:29115847-29121527:-1;chr14:41606973-41672179:-1;chr14:84040576-84053462:-1;chr15:44134089-44140792:-1;chr15:98839166-98846740:-1;chr16:19942815-19970111:-1;chr16:58671655-58679585:-1;chr16:8063663-8070034:-1;chr18:40051191-40060344:-1;chr19:1947496-1954243:-1;chr19:35358488-35364082:-1;chr19:57472684-57478735:-1;chr1:1008696-33428101:1;chr1:102981985-118210856:1;chr1:104333229-160069178:-1;chr1:10532535-52086062:-1;chr1:10593721-22544984:-1;chr1:11000544-210352595:-1;chr1:11168798-210037600:-1;chr1:150207282-216546090:-1;chr1:150262096-220965516:-1;chr1:150267833-187360931:1;chr1:153924857-168223449:-1;chr1:173971109-186325486:-1;chr1:176021366-244022618:-1;chr1:176027486-210743602:1;chr1:176232171-183415615:-1;chr1:176662006-197116025:1;chr1:177243880-247265613:1;chr1:182809129-186315259:-1;chr1:182814024-245905715:1;chr1:186233169-186321810:1;chr1:187242483-223923379:-1;chr1:192433020-211838849:1;chr1:193312809-244172296:1;chr1:198301572-198313291:-1;chr1:203535803-241184504:-1;chr1:203660375-207790855:1;chr1:203738238-241394532:1;chr1:205493732-206227778:-1;chr1:2068550-227749001:1;chr1:208061423-212065304:1;chr1:22539918-26402564:-1;chr1:24470636-65806923:1;chr1:26491823-48278955:-1;chr1:27818230-53385947:1;chr1:30854615-76564199:-1;chr1:32828029-223917154:1;chr1:33387731-222083256:-1;chr1:33392618-228002678:1;chr1:35206835-186228869:1;chr1:41732082-208440994:1;chr1:42174094-62123246:-1;chr1:43711284-172794913:-1;chr1:43715503-116711705:1;chr1:44021796-46794418:-1;chr1:46869357-110734126:-1;chr1:47080149-57895203:1;chr1:48268839-70823296:-1;chr1:53388571-203532748:1;chr1:65434646-214126453:1;chr1:68578726-236343140:-1;chr1:70600665-227181629:1;chr1:71544272-187249590:-1;chr1:78381334-174930142:1;chr1:78438651-247270878:-1;chr1:82290565-226955829:-1;chr1:85083954-93405396:-1;chr1:86677932-86684957:-1;chr1:88286998-211865281:-1;chr1:92136276-102979292:1;chr1:9383812-115549141:1;chr1:94361854-173979899:-1;chr1:9649603-11175913:-1;chr22:19098103-19103450:-1;chr22:19568850-19575804:-1;chr22:22703334-22752441:1;chr2:108852881-108859177:-1;chr2:140990927-140997449:-1;chr2:163663230-163668712:-1;chr2:16940093-16949702:-1;chr2:196169811-196176361:-1;chr2:38956022-38972572:1;chr3:131986063-131998357:-1;chr3:165038483-165086313:-1;chr3:189222922-189227688:-1;chr3:189734079-189743455:-1;chr3:26447844-26454823:-1;chr3:41086972-41147816:-1;chr3:53024162-53041943:-1;chr3:84102144-84110568:-1;chr3:89391108-89422305:-1;chr4:175622591-175629943:-1;chr4:64131648-64157031:-1;chr4:71192597-71202301:-1;chr4:77835705-77840925:-1;chr5:150788348-150795389:-1;chr5:170127275-170133922:-1;chr5:179273528-179279633:-1;chr5:82479176-82485709:-1;chr5:88039999-88046084:-1;chr6:110393354-110417123:-1;chr6:132704943-132715688:-1;chr6:67005854-67050972:-1;chr6:74610890-74623068:-1;chr6:77433996-77461537:-1;chr7:127212044-127220658:-1;chr7:157730840-157736827:-1;chr8:5592539-5607475:-1;chr8:63032223-63043589:-1;chr8:87185470-87196722:-1;chr9:35978649-35984566:-1;chrX:11950774-11961984:-1;chrX:19463498-19472538:-1;chrX:91675313-91682189:-1;chrY:15715619-15733808:-1 hs1:54948487-54951659,hs2:16471642-16474882;hs1:168420447-168423941,hs8:30104833-30105849;hs1:215363951-215367234,hs2:15382398-15385750;hs2:808016-810857,hs3:15938261-15938856;hs2:39633376-39636378,hs5:126611809-126614967;hs5:21901609-21902330,hs13:61461250-61462231;hs5:80098576-80099975,hsX:29351349-29353077;hs1:1004867-1007660,hs1:48276716-48279021;hs1:1685962-1688147,hs1:159504785-159507102;hs1:4202418-4204433,hs1:4204549-4206063;hs1:6408891-6411178,hs1:44046003-44049001;hs1:6853393-6855834,hs1:8436418-8438863;hs1:6859214-6861316,hs1:47451425-47453557;hs1:8713341-8715164,hs1:163725403-163727518;hs1:9653601-9656094,hs1:235001227-235003141;hs1:10538687-10541143,hs1:39547723-39550155;hs1:10598035-10600813,hs1:184466137-184469221;hs1:10706786-10709474,hs1:227749851-227752064;hs1:10975755-10978962,hs1:82296483-82299429;hs1:11008495-11010874,hs1:211841853-211844204;hs1:15062466-15065058,hs1:202893997-202896280;hs1:21891623-21894398,hs1:211855786-211858232;hs1:21959686-21962265,hs1:85009249-85011179;hs1:23243501-23245597,hs1:76492376-76494808;hs1:23291097-23294022,hs1:175245472-175247940;hs1:24465977-24468106,hs1:33167271-33169437;hs1:25156470-25158623,hs1:25161550-25164564;hs1:26395646-26398296,hs1:165169781-165172145;hs1:35005180-35006837,hs1:35007277-35009059;hs1:36639361-36641627,hs1:97428248-97430881;hs1:38973578-38975999,hs1:161359375-161361020;hs1:41406644-41408702,hs1:98932089-98934354;hs1:41475631-41478286,hs1:156479673-156482383;hs1:42178727-42181808,hs1:207549769-207552778;hs1:43279431-43282744,hs1:203732827-203736051;hs1:44198440-44200976,hs1:240852477-240854708;hs1:46810408-46813517,hs1:113418964-113421203;hs1:46861784-46864050,hs1:65810159-65812168;hs1:47447402-47449515,hs1:48055381-48057310;hs1:48059069-48061876,hs1:113423955-113426449;hs1:50705802-50708301,hs1:62003696-62006009;hs1:53782147-53784713,hs1:76238814-76240931;hs1:55024717-55027806,hs1:215735300-215738315;hs1:55701481-55704600,hs1:76242348-76245089;hs1:61858804-61861319,hs1:94369291-94371710;hs1:64635805-64638456,hs1:226583614-226586623;hs1:68097936-68100112,hs1:70817359-70819775;hs1:70327974-70330950,hs1:244246462-244249416;hs1:72615148-72618081,hs1:246576838-246579890;hs1:73049431-73052384,hs1:236398123-236401242;hs1:75770238-75772935,hs1:78445665-78448617;hs1:76499406-76502397,hs1:240285872-240288865;hs1:76555857-76557237,hs1:237231736-237233711;hs1:78374901-78377887,hs1:92130283-92133150;hs1:78870580-78873140,hs1:178466998-178469379;hs1:80109221-80111717,hs1:88293864-88296162;hs1:84708839-84711939,hs1:84715987-84718926;hs1:85004459-85006940,hs1:93397676-93400417;hs1:88273632-88276022,hs1:97433161-97435773;hs1:93381390-93383805,hs1:244465944-244468810;hs1:94346331-94348199,hs1:179195487-179197811;hs1:94366009-94367677,hs1:197548454-197550704;hs1:94366294-94367355,hs1:98926766-98927640;hs1:106113682-106115553,hs1:106113951-106117041;hs1:109813759-109815933,hs1:245579744-245582304;hs1:110573636-110576667,hs1:178527725-178530659;hs1:110727325-110729699,hs1:160589953-160592924;hs1:118215481-118218147,hs1:156339580-156342638;hs1:150211557-150214395,hs1:156659555-156662086;hs1:155824451-155826686,hs1:180811219-180813792;hs1:159508808-159510890,hs1:160920750-160923290;hs1:159861791-159864377,hs1:213924590-213927331;hs1:160061261-160063540,hs1:193278572-193280998;hs1:175242224-175245013,hs1:200179915-200182628;hs1:176839096-176841881,hs1:246572417-246575095;hs1:179192516-179194607,hs1:186308734-186310863;hs1:179698201-179700026,hs1:239180603-239182426;hs1:183407808-183410091,hs1:246883310-246885658;hs1:184461077-184463465,hs1:222075227-222077066;hs1:197544101-197547147,hs1:247997819-248001009;hs1:202206778-202209116,hs1:203526291-203528710;hs1:207010746-207012201,hs1:244177339-244178891;hs1:207544188-207546320,hs1:216564593-216567900;hs1:209135301-209136518,hs1:209136699-209138725;hs1:210029323-210031999,hs1:244461948-244464370;hs1:210346789-210348711,hs1:246990991-246993596;hs1:210822879-210825489,hs1:244250873-244253356;hs1:233469009-233470734,hs1:233471044-233472495;hs1:241398998-241401329,hs1:246886656-246888921;hs1:245770553-245772243,hs1:246998019-246999570;hs1:245908135-245910787,hs1:248004857-248007286;hs2:1955381-1958265,hs2:1956487-1959062;hs2:6647982-6649365,hs2:6650200-6651393;hs2:12329264-12332171,hs2:12913976-12916959;hs2:12336024-12338403,hs2:16688374-16691199;hs2:16477178-16479753,hs2:16790801-16793554;hs2:16683391-16685511,hs2:16785467-16787685;hs2:17989511-17992112,hs2:17989477-17993459;hs2:24701899-24703548,hs2:24703653-24705579;hs2:27902226-27903731,hs2:27903741-27905317;hs2:33786062-33787088,hs2:33787326-33789079;hs2:34693030-34695774,hs2:34736592-34739132;hs2:116148701-116150175,hs2:116150399-116152155;hs2:170103924-170104725,hs2:170111152-170113635;hs2:194337596-194338905,hs2:194339579-194340321;hs2:206859333-206860348,hs2:206861070-206861947;hs2:241722455-241726263,hs2:241724618-241727887;hs3:10264287-10265503,hs3:10266393-10267298;hs3:21940103-21940839,hs3:21941237-21942512;hs3:182887667-182889159,hs3:182889590-182891274;hs3:192193122-192194795,hs3:192195192-192196836;hs4:7449442-7450211,hs4:7451514-7452390;hs4:12787560-12789186,hs4:12789223-12791393;hs4:29320749-29321478,hs4:29321999-29322835;hs4:83383405-83385172,hs4:83385265-83387216;hs4:108476106-108477333,hs4:108477791-108479150;hs4:151723485-151725174,hs4:151725185-151727143;hs4:166001127-166002556,hs4:166005082-166007856;hs4:166461090-166462609,hs4:166462523-166464428;hs4:173422375-173425022,hs4:173433624-173436300;hs4:173966683-173969901,hs4:173968108-173971188;hs5:14633524-14635264,hs5:14635359-14637049;hs5:83945384-83947933,hs5:83954903-83957608;hs5:86295853-86299812,hs5:86297718-86301231;hs5:91230527-91232071,hs5:91232551-91234015;hs5:114288441-114290549,hs5:114289048-114292731;hs5:118834421-118836079,hs5:118836613-118838299;hs5:145552445-145553844,hs5:145554135-145555699;hs6:2692806-2694838,hs6:2694759-2696011;hs6:35623647-35626235,hs6:35629812-35631162;hs6:53926271-53928740,hs6:53934807-53937634;hs6:85315475-85318184,hs6:85324329-85327036;hs6:105942262-105943811,hs6:105944066-105945755;hs6:156027142-156028443,hs6:156029333-156030501;hs6:160618547-160621975,hs6:160620186-160623996;hs6:160876145-160878035,hs6:160877688-160879934;hs6:165722187-165724689,hs6:165732116-165735298;hs6:168714935-168716965,hs6:168718746-168721093;hs7:44198880-44200567,hs7:44200672-44201762;hs7:54798692-54799866,hs7:54800391-54801424;hs7:109565017-109568792,hs7:109566187-109569526;hs7:123478248-123478797,hs7:123479739-123480685;hs7:148069549-148072803,hs7:148076323-148079104;hs8:11243901-11245456,hs8:11247278-11249947;hs8:17288594-17291420,hs8:17563830-17566379;hs8:24332976-24335870,hs8:24687257-24690111;hs8:75086663-75088327,hs8:75090940-75093499;hs8:88378593-88379554,hs8:88379949-88381515;hs8:117760738-117762045,hs8:117762091-117763829;hs8:143581949-143583688,hs8:143583883-143585793;hs9:6379668-6381105,hs9:6387719-6389027;hs9:14679198-14680487,hs9:14680854-14682041;hs9:136888982-136890229,hs9:136891121-136892427;hs9:137353705-137357195,hs9:137358135-137361462;hs10:6934861-6938294,hs10:6936531-6938559;hs10:64009586-64012305,hs10:64011094-64013037;hs10:111142103-111144247,hs10:111142838-111145865;hs11:5781536-5784427,hs11:5809325-5811807;hs11:67265086-67266716,hs11:67267018-67268925;hs11:93967487-93969838,hs11:93969736-93973473;hs11:98270753-98272419,hs11:98272602-98274480;hs12:7106121-7107423,hs12:7108387-7109342;hs12:131264374-131266514,hs12:131266547-131268502;hs12:132070874-132073090,hs12:132073104-132074954;hs13:85819530-85820361,hs13:85820808-85822429;hs13:113812712-113816523,hs13:113814855-113816880;hs14:59907761-59909025,hs14:59909057-59910575;hs14:86841030-86844584,hs14:86843137-86846405;hs14:99581720-99583798,hs14:99583906-99585245;hs15:39369611-39372318,hs15:39373646-39376151;hs16:67622903-67626347,hs16:67624909-67627458;hs16:75097273-75101172,hs16:75098506-75102161;hs16:76713713-76716211,hs16:76719205-76721612;hs16:89110492-89112929,hs16:89112643-89114280;hs17:46165604-46166797,hs17:46167118-46168492;hs17:55870749-55871735,hs17:55871818-55873921;hs17:67203543-67204889,hs17:67205459-67206715;hs17:71399614-71401392,hs17:71401643-71402954;hs17:73068481-73070434,hs17:73070645-73072269;hs18:1790538-1791925,hs18:1792494-1794103;hs18:10148809-10150891,hs18:10150760-10152711;hs19:51437103-51438234,hs19:51438541-51440246;hs20:32812685-32815962,hs20:32819267-32822057;hs20:57403493-57405434,hs20:57405728-57407379;hs20:61385018-61387032,hs20:61387173-61388672;hs21:22177282-22177971,hs21:22178347-22179403;hs21:38998378-38999172,hs21:39000470-39001302;hs22:17767992-17770384,hs22:17779129-17782116;hs22:33777986-33780343,hs22:33783339-33785347;hs22:34993604-34995795,hs22:34995840-34997424;hs22:35871259-35872771,hs22:35872800-35874992;hsX:92793640-92796227,hsX:92801775-92804228 ABCA10;ABL2;ACOT11;ACOT7;ADAM7;ALPL;ANKRD13C;ANP32E;ASPM;ASTN1;ATP2B4;AVPR1B;BAI1;C1orf127;C1orf21;C5orf45;C6orf118;C8orf12;CABS1;CAMTA1;CAPN2;CASZ1;CBX1;CCDC19;CCDC23;CD34;CDC42BPA;CDH12;CDK18;CELSR2;CLIC4;CNBD1;CNTNAP2;CR1;CRTC2;CSNK1G2;CTCF;CTPS;DAB1;DACT2;DENND1B;DFFA;DGCR2;DHX9;DIEXF;DNAJC6;DNTTIP2;DPP10;ECHDC2;EIF3H;EPHA3;ERO1LB;FAAH;FAM49A;FAM5B;FAM69A;FGF12;FKBP5;FMN2;FUBP1;GALM;GALNTL6;GCK;GCLM;GLRA3;GNAS-AS1;GON4L;GPR137B;HHAT;HHLA3;HIVEP3;HSD17B4;IGSF8;IL19;IL1RAPL1;IL22RA1;INO80D;IRAK2;ITLN2;KAZN;KCNH7;KCNIP1;KCNJ6;KCNK2;KIAA1804;KIF1A;KIF26B;KLHL12;LARGE;LARS;LAX1;LEPREL1;LGR6;LINC00094;LINC00320;LOC100505832;LOC339529;LOC339822;LOC388630;LPCAT3;LPHN2;LRBA;LRP1B;LRP2;LRP8;LRRC7;MACF1;MAP3K15;MAP4K3;MAP7D1;MARC1;MEF2C;MIR548F1;MIR548O2;MLIP;MOB3C;MOXD1;MRPS21;MSH3;MTOR;MTUS1;MYLK4;MYT1L;NADK;NBAS;NEGR1;NEK2;NEXN;NFIA;NRG3;NSUN4;NTSR1;OR11L1;OR52N1;OSBPL9;PAPPA2;PARP1;PCDH11X;PEX14;PITPNM1;PRKCZ;PROZ;PTPRF;PTPRN2;RABGAP1L;RAP1GAP;RASGRP3;RERE;RFWD2;RGS7;RHBG;RNF19B;RNF223;ROR1;RTKN2;RYR2;SDK2;SFMBT1;SLAMF1;SLC44A5;SLC4A1AP;SLC6A17;SMYD3;SORCS2;SPSB1;ST3GAL3;ST6GALNAC3;SYNC;TMEM192;TMEM201;TPR;TRIM63;TSSK3;USH2A;WASF2;WDR65;WDR76;WLS;XPR1;XRCC4;ZDHHC21;ZNRF1;ZRANB2 Inserm, U900, Paris, France Neuroblastoma is a pediatric cancer of the peripheral nervous system in which structural chromosome aberrations are emblematic of aggressive tumors. In this study, we performed an in-depth analysis of somatic rearrangements in two neuroblastoma cell lines and two primary tumors using paired-end sequencing of mate-pair libraries and RNA-seq. The cell lines presented with typical genetic alterations of neuroblastoma and the two tumors belong to the group of neuroblastoma exhibiting a profile of chromothripsis. Inter and intra-chromosomal rearrangements were identified in the four samples, allowing in particular characterization of unbalanced translocations at high resolution. Using complementary experiments, we further characterized 51 rearrangements at the base pair resolution that revealed 59 DNA junctions. In a subset of cases, complex rearrangements were observed with templated insertion of fragments of nearby sequences. Although we did not identify known particular motifs in the local environment of the breakpoints, we documented frequent microhomologies at the junctions in both chromothripsis and non-chromothripsis associated breakpoints. RNA-seq experiments confirmed expression of several predicted chimeric genes and genes with disrupted exon structure including ALK, NBAS, FHIT, PTPRD and ODZ4. Our study therefore indicates that both non-homologous end joining-mediated repair and replicative processes may account for genomic rearrangements in neuroblastoma. RNA-seq analysis allows the identification of the subset of abnormal transcripts expressed from genomic rearrangements that may be involved in neuroblastoma oncogenesis. GRCh37/hg19 ERP001414;ERP001988 Yes ANP32E,USH2A;ATP2B4,CR1;CDK18,AVPR1B;DFFA,OSBPL9;DHX9,TPR;FAAH,SLC6A17;IL22RA1,DNAJC6;KCNK2,NBAS;LAX1,RGS7;LOC388630,HHLA3;MIR548F1,TPR;MOB3C,DAB1;NEXN,RABGAP1L;PAPPA2,ASPM;RFWD2,HHAT;TMEM201,MTOR;TSSK3,CAPN2;WASF2,ECHDC2;WLS,GPR137B CTDB0043 Research 23991058 Valentina Boeva, Stephanie Jouannet, Romain Daveau, Valerie Combaret, Cecile Pierre-Eugene, Alex Cazes, Caroline Louis-Brennetot, Gudrun Schleiermacher, Sandrine Ferrand, Gaelle Pierron, Alban Lermine, Thomas Rio Frio, Virginie Raynal, Gilles Vassal, Emma Breakpoint Features of Genomic Rearrangements in Neuroblastoma with Unbalanced Translocations and Chromothripsis PLoS One 2013 Aug 6,19 Neuroblastoma Next Generation Sequencing Homo sapiens NB1142 Illumina Genome Analyzer Iix + SOLiD V4/5500 chr10:132985660-132995251:-1;chr10:1579059-1588908:-1;chr10:15954855-15968097:-1;chr10:71277735-71295026:-1;chr10:81721053-81731645:-1;chr11:124771072-124781839:-1;chr11:7807484-7837743:-1;chr12:56912991-56959884:1;chr13:106702169-106722732:-1;chr14:25905886-25916204:-1;chr16:52409891-52418832:-1;chr16:83667149-83679289:-1;chr17:69601715-69610672:-1;chr19:15539293-51327008:-1;chr19:19726050-33382212:-1;chr19:19730038-59064493:1;chr19:39272147-51322273:1;chr19:47844171-59068942:-1;chr19:54189926-55853550:1;chr19:562142-11115016:-1;chr19:781621-21513741:-1;chr1:155589112-155726967:1;chr1:199107104-199117349:-1;chr1:248150477-248159424:-1;chr1:60043981-60054277:-1;chr1:66020112-66033875:-1;chr20:12454760-12479026:-1;chr21:18101423-18108767:-1;chr21:25254696-25267775:-1;chr21:45615676-45624372:-1;chr2:143453088-143465894:-1;chr2:208347634-208363143:-1;chr2:227558825-227568040:-1;chr2:235838370-235846454:-1;chr2:35577680-35620309:-1;chr2:79330714-79343389:1;chr3:107034072-107044826:-1;chr3:196930241-196943330:-1;chr3:2023912-2032848:-1;chr3:25026175-25036053:-1;chr3:46791915-46854633:-1;chr4:115504089-115517922:-1;chr4:122279125-122293394:-1;chr4:164610228-164619218:-1;chr4:17198756-17207600:-1;chr4:32514066-32524007:-1;chr5:150877792-150886768:-1;chr5:26792444-26806239:-1;chr5:7639502-7649315:-1;chr5:86965343-86976794:-1;chr5:9896902-9928889:-1;chr6:100534810-100542871:-1;chr6:108911690-108920587:-1;chr6:126097658-150070724:1;chr6:136006752-170470886:-1;chr6:219613-107430301:1;chr6:23738625-23748789:-1;chr6:33736589-111279330:1;chr6:35335168-67817228:-1;chr6:35754594-35766766:1;chr6:39435171-108400197:-1;chr6:52174676-52932227:-1;chr6:52924112-87848352:-1;chr6:53924807-53938573:-1;chr6:62450477-159553363:1;chr6:73332512-160539393:1;chr6:99365311-168647732:1;chr7:13274204-13284668:-1;chr8:16259283-16277307:-1;chr8:2253552-2268331:1;chr9:96218633-96229100:-1;chrX:146034707-146045627:-1 hs2:138746679-138747353,hsX:76651556-76652306;hs6:215500-218685,hs19:55556975-55560020;hs6:35142422-35145938,hs19:55596935-55599944;hs6:37524902-37528250,hs19:55573613-55577027;hs6:45986874-45990519,hs19:55577842-55581128;hs6:125180750-125184366,hs19:55654991-55658179;hs6:136611902-136612700,hs19:55560202-55560883;hs6:152045747-152048420,hs19:55013679-55017070;hs6:157558280-157559463,hs19:55552600-55554363;hs6:157640190-157641292,hs19:55553991-55555948;hs6:160530367-160533917,hs19:55649962-55653924;hs17:21195702-21196569,hs18:15165041-15165590;hs1:3497291-3500128,hs1:3500363-3502804;hs1:28546763-28551211,hs1:28554059-28557093;hs1:106112685-106113998,hs1:106114598-106116634;hs1:113540719-113541837,hs1:113543186-113545023;hs1:219159258-219161464,hs1:219160830-219164490;hs1:227598318-227600253,hs1:227600264-227602390;hs1:246680458-246683437,hs1:246685322-246689142;hs2:71842780-71845722,hs2:71845556-71847897;hs2:104041156-104042668,hs2:104043987-104045472;hs2:108850805-108855426,hs2:108856247-108859628;hs2:166011059-166014630,hs2:166016836-166020285;hs2:180998391-181000046,hs2:181000523-181001747;hs2:194922032-194923154,hs2:194924830-194926182;hs2:195293240-195297166,hs2:195298592-195302232;hs3:3476764-3481012,hs3:3483369-3487391;hs3:18828208-18829399,hs3:18830672-18832075;hs3:22859858-22862035,hs3:22862828-22863813;hs3:32715304-32716156,hs3:32717142-32718337;hs3:39759108-39761179,hs3:39762318-39764259;hs3:42834260-42838401,hs3:42840869-42844527;hs3:174478186-174479914,hs3:174480147-174482224;hs3:183376919-183379044,hs3:183379086-183381759;hs4:1037556-1040435,hs4:1039753-1041425;hs4:10207226-10211271,hs4:10234580-10238735;hs4:19076032-19079475,hs4:19085750-19090524;hs4:137070698-137073394,hs4:137076171-137079269;hs4:152786696-152789884,hs4:152794800-152799109;hs4:189956531-189957543,hs4:189958600-189959209;hs5:21232204-21237237,hs5:21238515-21242985;hs5:109565750-109567478,hs5:109568734-109570623;hs5:114320517-114325263,hs5:114334985-114339220;hs6:35146380-35149594,hs6:71696846-71700967;hs6:35339473-35343551,hs6:52179146-52183214;hs6:37520118-37523236,hs6:108432031-108435299;hs6:39045094-39048407,hs6:62444279-62448067;hs6:39401847-39404731,hs6:160535975-160539067;hs6:49593450-49597312,hs6:170725950-170729952;hs6:52174742-52177612,hs6:64986030-64990307;hs6:64982285-64985665,hs6:126222575-126226244;hs6:64999063-65000516,hs6:65000972-65003277;hs6:67004893-67008689,hs6:67048927-67052957;hs6:67808955-67812730,hs6:95859383-95863573;hs6:71691783-71695322,hs6:122279176-122282712;hs6:73713582-73715765,hs6:73716078-73718288;hs6:73991925-73996338,hs6:126227352-126231084;hs6:84569987-84573247,hs6:90539496-90543057;hs6:87840419-87844059,hs6:99355361-99359121;hs6:90535144-90538047,hs6:99276177-99279776;hs6:95865284-95868629,hs6:159241278-159244471;hs6:99271810-99275631,hs6:126092793-126096866;hs6:108435896-108440138,hs6:111280630-111284071;hs6:109694349-109698659,hs6:156445677-156449341;hs6:151888147-151891900,hs6:168197596-168201129;hs6:160527913-160531976,hs6:170730583-170734012;hs7:23093513-23096892,hs7:23105700-23109552;hs7:89806779-89810419,hs7:89812589-89817401;hs8:4977765-4979757,hs8:4980529-4982653;hs8:16197107-16201271,hs8:16207525-16211327;hs8:20899338-20900657,hs8:20901268-20903383;hs8:87172224-87173897,hs8:87175253-87176798;hs8:109134409-109135774,hs8:109135988-109137515;hs8:131039045-131041191,hs8:131041638-131043476;hs8:133919998-133920718,hs8:133922004-133923155;hs9:1802653-1804668,hs9:1805774-1807266;hs9:6726101-6728026,hs9:6728674-6730171;hs9:17397400-17401383,hs9:17407033-17411101;hs9:20590634-20591705,hs9:20592586-20593798;hs9:22492851-22496249,hs9:22504340-22507637;hs9:35492814-35494813,hs9:35495808-35497072;hs9:138240701-138241833,hs9:138242008-138243104;hs9:139928004-139929109,hs9:139931191-139931918;hs10:12452751-12457959,hs10:12455503-12459309;hs10:65504243-65509088,hs10:65511385-65515104;hs10:94130431-94134544,hs10:94137823-94141682;hs10:121711462-121713232,hs10:121714452-121716243;hs11:12657307-12661483,hs11:12662483-12664084;hs11:18398708-18399786,hs11:18400400-18401844;hs11:29963166-29967574,hs11:29968718-29972808;hs11:31389408-31393799,hs11:31397791-31402349;hs11:35267273-35270363,hs11:35270272-35273033;hs11:41829657-41831543,hs11:41831921-41834084;hs11:47448092-47452190,hs11:47450993-47453769;hs11:60380863-60384604,hs11:60424422-60428555;hs11:66160946-66164420,hs11:66162090-66164415;hs11:78588395-78590314,hs11:78591095-78593463;hs11:102599019-102602022,hs11:102601578-102604617;hs12:13107584-13109278,hs12:13109781-13111872;hs12:25740157-25742633,hs12:25741010-25745706;hs12:33293303-33296552,hs12:33307675-33309156;hs12:72184687-72189140,hs12:72190579-72193446;hs12:75007328-75008701,hs12:75010204-75011759;hs12:121950420-121952916,hs12:121953040-121955408;hs12:132398693-132401848,hs12:132400522-132404849;hs13:99255912-99257184,hs13:99258928-99260132;hs13:108944261-108946841,hs13:108951780-108955425;hs14:34672092-34673914,hs14:34675174-34676937;hs14:65838664-65843138,hs14:65842788-65846787;hs14:86769656-86772801,hs14:86784991-86789162;hs14:89148654-89150216,hs14:89150865-89152505;hs15:59128046-59129248,hs15:59130206-59132032;hs15:99629234-99630148,hs15:99630360-99631834;hs15:100928509-100931556,hs15:100931318-100932355;hs16:87019239-87019956,hs16:87020696-87022476;hs17:2254327-2259504,hs17:2260492-2263649;hs17:7204607-7205843,hs17:7205999-7207026;hs17:28395571-28398084,hs17:28398425-28400597;hs17:51406845-51409338,hs17:51409729-51412054;hs17:54867150-54868893,hs17:54870207-54871705;hs17:75641693-75642704,hs17:75644358-75645659;hs17:79324700-79325820,hs17:79326896-79327785;hs18:54727608-54728861,hs18:54730491-54731891;hs18:69614804-69616515,hs18:69617466-69618256;hs19:568253-571413,hs19:47848514-47852973;hs19:785786-789292,hs19:43966380-43970074;hs19:15543728-15548327,hs19:43962211-43965834;hs19:18549935-18552093,hs19:18552794-18554984;hs19:33373668-33377310,hs19:39267187-39271185;hs20:8640806-8642403,hs20:8643720-8645207;hs20:15297703-15301746,hs20:15303839-15308063;hs20:46817371-46818628,hs20:46819137-46820358;hs20:56547335-56549934,hs20:56550007-56553092;hs21:27161687-27163437,hs21:27163613-27165657;hs21:31940863-31941546,hs21:31943899-31944758;hs21:46642249-46644429,hs21:46645270-46647624;hs22:27163628-27168056,hs22:27169893-27173887;hsX:77523668-77525048,hsX:77525576-77528157;hsX:81993917-81995014,hsX:81993861-81996861;hsX:106834525-106835691,hsX:106836039-106837415;hsX:111950965-111952863,hsX:111953697-111955739;hsX:121873675-121875935,hsX:121875797-121877521;hsX:136395767-136397144,hsX:136398768-136399997;hsX:147506452-147509429,hsX:147511230-147515724;hsX:152194567-152195283,hsX:152197532-152198274 ADARB1;ADARB2;ADCY2;BCLAF1;BEND3;C17orf67;C6orf127;C6orf97;C9orf139;CAMK1D;CASP8AP2;CD164;CDH13;CEP89;CHMP2A;CLIC5;CLPS;CNTLN;CYB5R4;DCDC1;DLG1;DNAJC24;DNAJC8;DYSF;EFCAB5;EML5;EPS8L1;ESR1;EYS;EZR;FAM120A;FAM63B;FAT2;FBXL4;FBXO9;FGGY;FOXO3;GLP1R;GON4L;GPR77;GTF3C6;HIGD1A;HNMT;ICK;IFLTD1;ISYNA1;KCNQ5;KDM2B;KDM4C;KHDC1;KHDRBS2;KIF6;KLHL24;KLK1;LEPR;LINC00271;LINC00301;LOC255654;LOC285692;LOC344595;LYPD3;MACROD2;MAP2K3;MARCH1;MEGF6;MIR1283-1;MIR4462;MLIP;MLLT3;NCOA7;NUP43;ODZ4;OR2L13;PBX4;PLCB1;PPARD;PSMC3;QRFPR;RBMS2;RDH13;RHAG;RUSC2;SCN3A;SGSM2;SMARCA4;TCERG1L;TG;TNFSF13B;TNNT1;TRIM28;ULK1;WIZ;ZNF708 Inserm, U900, Paris, France Neuroblastoma is a pediatric cancer of the peripheral nervous system in which structural chromosome aberrations are emblematic of aggressive tumors. In this study, we performed an in-depth analysis of somatic rearrangements in two neuroblastoma cell lines and two primary tumors using paired-end sequencing of mate-pair libraries and RNA-seq. The cell lines presented with typical genetic alterations of neuroblastoma and the two tumors belong to the group of neuroblastoma exhibiting a profile of chromothripsis. Inter and intra-chromosomal rearrangements were identified in the four samples, allowing in particular characterization of unbalanced translocations at high resolution. Using complementary experiments, we further characterized 51 rearrangements at the base pair resolution that revealed 59 DNA junctions. In a subset of cases, complex rearrangements were observed with templated insertion of fragments of nearby sequences. Although we did not identify known particular motifs in the local environment of the breakpoints, we documented frequent microhomologies at the junctions in both chromothripsis and non-chromothripsis associated breakpoints. RNA-seq experiments confirmed expression of several predicted chimeric genes and genes with disrupted exon structure including ALK, NBAS, FHIT, PTPRD and ODZ4. Our study therefore indicates that both non-homologous end joining-mediated repair and replicative processes may account for genomic rearrangements in neuroblastoma. RNA-seq analysis allows the identification of the subset of abnormal transcripts expressed from genomic rearrangements that may be involved in neuroblastoma oncogenesis. GRCh37/hg19 ERP001414;ERP001988 Yes BCLAF1,RDH13;C6orf127,CLPS;CLIC5,RDH13;GPR77,CHMP2A;MIR4462,RDH13;PBX4,CEP89;PBX4,TRIM28;WIZ,KLK1 CTDB0046 Research 23612016 Bassaganyas L, Bea S, Escaramis G, Tornador C, Salaverria I, Zapata L, Drechsel O, Ferreira PG, Rodriguez-Santiago B, Tubio JM, Navarro A, Martin-Garcia D, Lopez C, Martinez-Trillos A, Lopez-Guillermo A, Gut M, Ossowski S, Lopez-Otin C, Campo E, Estivill Sporadic and reversible chromothripsis in chronic lymphocytic leukemia revealed by longitudinal genomic analysis Leukemia 2013 May 1,6,10,12 Chronic lymphocytic leukemia Next Generation Sequencing Homo sapiens 016-T02 Illumina HiSeq 2000 + Illumina Genome Analyzer Iix chr1:158916616-162228238:-1;chr1:204884807-207098441:-1;chr1:245750841-245754210:1;chr2:57538505-57546240:-1;chr3:66307700-66848190:-1;chr4:92032232-92035673:-1;chr4:55259599-190916819:1;chr6:21165446-21202889:-1;chr6:42655943-44314131:-1;chr6:87787340-87937492:-1;chr6:87831293-92372455:-1;chr6:98726379-1009453032:-1;chr6:105121236-107322576:-1;chr6:135571668-137893724:-1;chr7:142493998-142495773:-1;chr9:19557108-19559274:-1;chr10:103329084-105060989:-1;chr12:6174700-8452800:-1;chr12:10781231-13107215:-1;chr14:106330475-107178831:-1;chr18:118560-14978275:-1 hs1:158895420-158895420,hs12:9009852-9009852;hs1:158895935-158895935,hs1:207100978-207100978;hs1:158908565-158908565,hs1:204868609-204868609;hs1:162273578-162273578,hs10:103313969-103313969;hs1:162299645-162299645,hs1:207110393-207110393;hs1:204873185-204873185,hs1:13128829-13128829;hs1:204884852-204884852,hs6:87790817,87790817;hs1:204885286-204885286,hs10:103311319-103311319;hs1:207109744-207109744,hs6:98720478-98720478;hs4:49275540-49275540,hs18:14983384-14983384;hs6:87823275-87823275,hs6:98688205-98688205;hs6:92369212-92369212,hs6:100987026-100987026;hs6:92405452-92405452,hs10:103302215-103302215;hs6:92106400-92406400,hs6:137889638-137889638;hs6:92407820-92407820,hs6:100973954-100973954;hs6:137871508-137871508,hs12:10749843-10749843;hs10:70172296-70172296,hs3:168885793-168885793;hs10:101290756-101290756,hs2:89132330-89132330;hs10:103308280-103308280,hs6:98688129-98688129;hs10:103310475-103310475,hs6:100949176-100949176;hs10:103328997-103328997,hs6:100987263-100987263;hs10:105080595-105080595,hs6:137868980-137868980;hs12:5988079-5988079,hs6:92374031-92374031;hs12:5998576-5998576,hs6:87786886-87786886;hs12:10749697-10749697,hs10:105073574-105073574;hs12:10766354-10766354,hs6:87823973-87823973;hs12:13102811-13102811,hs12:13123781-13123781;hs12:13127322-13127322,hs1:162299794;hs17:61565839-61565839,hs5:100389381 NFKB2;UBR2;SPATS1 Center for Genomic Regulation (CRG), Barcelona, Spain GRCh37/hg19 Yes UBR2,SPATS1 CTDB0051 Research 23738515 Mehine M, Kaasinen E, Makinen N, Katainen R, Kampjarvi K, Pitkanen E, Heinonen HR, Butzow R, Kilpivaara O, Kuosmanen A, Ristolainen H, Gentile M, Sjoberg J, Vahteristo P, Aaltonen LA Characterization of Uterine Leiomyomas by Whole-Genome Sequencing N Engl J Med 2013 Jun 1,17 Uterine leiomyoma Next Generation Sequencing Homo sapiens MY10m3 Illumina + Complete Genomics TP53;NF1 Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland BACKGROUND: Uterine leiomyomas are benign but affect the health of millions of women. A better understanding of the molecular mechanisms involved may provide clues to the prevention and treatment of these lesions. METHODS: We performed whole-genome sequencing and gene-expression profiling of 38 uterine leiomyomas and the corresponding myometrium from 30 women. RESULTS: Identical variants observed in some separate tumor nodules suggested that these nodules have a common origin. Complex chromosomal rearrangements resembling chromothripsis were a common feature of leiomyomas. These rearrangements are best explained by a single event of multiple chromosomal breaks and random reassembly. The rearrangements created tissue-specific changes consistent with a role in the initiation of leiomyoma, such as translocations of the HMGA2 and RAD51B loci and aberrations at the COL4A5-COL4A6 locus, and occurred in the presence of normal TP53 alleles. In some cases, separate events had occurred more than once in single tumor-cell lineages. CONCLUSIONS: Chromosome shattering and reassembly resembling chromothripsis (a single genomic event that results in focal losses and rearrangements in multiple genomic regions) is a major cause of chromosomal abnormalities in uterine leiomyomas; we propose that tumorigenesis occurs when tissue-specific tumor-promoting changes are formed through these events. Chromothripsis has previously been associated with aggressive cancer; its common occurrence in leiomyomas suggests that it also has a role in the genesis and progression of benign tumors. We observed that multiple separate tumors could be seeded from a single lineage of uterine leiomyoma cells. GRCh37/hg19 ERP004006 Yes NA CTDB0052 Research 23738515 Mehine M, Kaasinen E, Makinen N, Katainen R, Kampjarvi K, Pitkanen E, Heinonen HR, Butzow R, Kilpivaara O, Kuosmanen A, Ristolainen H, Gentile M, Sjoberg J, Vahteristo P, Aaltonen LA Characterization of Uterine Leiomyomas by Whole-Genome Sequencing N Engl J Med 2013 Jun 2,5,7,22,X Uterine leiomyoma Next Generation Sequencing Homo sapiens MY23m4 Illumina + Complete Genomics COL4A5;COL4A6;CUX1 Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland BACKGROUND: Uterine leiomyomas are benign but affect the health of millions of women. A better understanding of the molecular mechanisms involved may provide clues to the prevention and treatment of these lesions. METHODS: We performed whole-genome sequencing and gene-expression profiling of 38 uterine leiomyomas and the corresponding myometrium from 30 women. RESULTS: Identical variants observed in some separate tumor nodules suggested that these nodules have a common origin. Complex chromosomal rearrangements resembling chromothripsis were a common feature of leiomyomas. These rearrangements are best explained by a single event of multiple chromosomal breaks and random reassembly. The rearrangements created tissue-specific changes consistent with a role in the initiation of leiomyoma, such as translocations of the HMGA2 and RAD51B loci and aberrations at the COL4A5-COL4A6 locus, and occurred in the presence of normal TP53 alleles. In some cases, separate events had occurred more than once in single tumor-cell lineages. CONCLUSIONS: Chromosome shattering and reassembly resembling chromothripsis (a single genomic event that results in focal losses and rearrangements in multiple genomic regions) is a major cause of chromosomal abnormalities in uterine leiomyomas; we propose that tumorigenesis occurs when tissue-specific tumor-promoting changes are formed through these events. Chromothripsis has previously been associated with aggressive cancer; its common occurrence in leiomyomas suggests that it also has a role in the genesis and progression of benign tumors. We observed that multiple separate tumors could be seeded from a single lineage of uterine leiomyoma cells. GRCh37/hg19 ERP004006 Yes COL4A5,COL4A6 CTDB0053 Research 23738515 Mehine M, Kaasinen E, Makinen N, Katainen R, Kampjarvi K, Pitkanen E, Heinonen HR, Butzow R, Kilpivaara O, Kuosmanen A, Ristolainen H, Gentile M, Sjoberg J, Vahteristo P, Aaltonen LA Characterization of Uterine Leiomyomas by Whole-Genome Sequencing N Engl J Med 2013 Jun 1,4,22 Uterine leiomyoma Next Generation Sequencing Homo sapiens MY46m1 Illumina + Complete Genomics Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland BACKGROUND: Uterine leiomyomas are benign but affect the health of millions of women. A better understanding of the molecular mechanisms involved may provide clues to the prevention and treatment of these lesions. METHODS: We performed whole-genome sequencing and gene-expression profiling of 38 uterine leiomyomas and the corresponding myometrium from 30 women. RESULTS: Identical variants observed in some separate tumor nodules suggested that these nodules have a common origin. Complex chromosomal rearrangements resembling chromothripsis were a common feature of leiomyomas. These rearrangements are best explained by a single event of multiple chromosomal breaks and random reassembly. The rearrangements created tissue-specific changes consistent with a role in the initiation of leiomyoma, such as translocations of the HMGA2 and RAD51B loci and aberrations at the COL4A5-COL4A6 locus, and occurred in the presence of normal TP53 alleles. In some cases, separate events had occurred more than once in single tumor-cell lineages. CONCLUSIONS: Chromosome shattering and reassembly resembling chromothripsis (a single genomic event that results in focal losses and rearrangements in multiple genomic regions) is a major cause of chromosomal abnormalities in uterine leiomyomas; we propose that tumorigenesis occurs when tissue-specific tumor-promoting changes are formed through these events. Chromothripsis has previously been associated with aggressive cancer; its common occurrence in leiomyomas suggests that it also has a role in the genesis and progression of benign tumors. We observed that multiple separate tumors could be seeded from a single lineage of uterine leiomyoma cells. GRCh37/hg19 ERP004006 Yes NA CTDB0054 Research 23738515 Mehine M, Kaasinen E, Makinen N, Katainen R, Kampjarvi K, Pitkanen E, Heinonen HR, Butzow R, Kilpivaara O, Kuosmanen A, Ristolainen H, Gentile M, Sjoberg J, Vahteristo P, Aaltonen LA Characterization of Uterine Leiomyomas by Whole-Genome Sequencing N Engl J Med 2013 Jun 1,2,11,15,X Uterine leiomyoma Next Generation Sequencing Homo sapiens MY47m1 Illumina + Complete Genomics chr1:215048026-223440603:1;chr1:31282315-44432520:1;chr22:42110013-42176601:-1;chr2:38218515-61540231:-1 hs1:19539160-19539160,hs2:217077076-217077076;hs1:31299824-31299824,hs11:118397268-118397268;hs1:32820625-32820625,hs11:114620180-114620180;hs1:33506263-33506263,hs1:44820517-44820517;hs1:33506872-33506872,hs1:220044420-220044420;hs1:52870556-52870556,hs6:151805925-151805925;hs1:52871037-52871037,hs11:12381161-12381161;hs1:67456934-67456934,hs11:17806872-17806872;hs1:93896730-93896730,hs1:97107552-97107552;hs1:97064269-97064269,hs6:161230570-161230570;hs1:97107169-97107169,hs5:6689935-6689935;hs1:100368634-100368634,hs15:86207345-86207345;hs1:100454228-100454228,hs2:63807137-63807137;hs1:114474067-114474067,hs2:12647369-12647369;hs1:145455240-145455240,hs1:156695207-156695207;hs1:145455307-145455307,hs1:150516696-150516696;hs1:145498335-145498335,hs1:168054990-168054990;hs1:145498420-145498420,hs1:150516666-150516666;hs1:145575509-145575509,hs1:156655269-156655269;hs1:145576476-145576476,hs1:156655352-156655352;hs1:150516666-150516666,hs1:150516747-150516747;hs1:151386388-151386388,hs22:42066919-42066919;hs1:220309075-220309075,hs2:61486886-61486886;hs2:3404675-3404675,hs2:62048799-62048799;hs2:5620094-5620094,hs2:62048871-62048871;hs2:5620209-5620209,hs2:5644328-5644328;hs2:5644274-5644274,hs2:28618421-28618421;hs2:12648413-12648413,hs2:15596270-15596270;hs2:17878699-17878699,hs2:61545621-61545621;hs2:17878813-17878813,hs2:64344610-64344610;hs2:28461740-28461740,hs15:86388593-86388593;hs2:28462611-28462611,hs15:86388847-86388847;hs2:28478069-28478069,hs11:118397907-118397907;hs2:61368528-61368528,hs2:61487406-61487406;hs2:61538447-61538447,hs2:64344463-64344463;hs2:61546020-61546020,hs2:63808163-63808163;hs2:217077076-217077076,hs11:65061312-65061312;hs2:217077154-217077154,hs15:57223400-57223400;hs6:137661579-137661579,hs22:19144224-19144224;hs6:161146302-161146302,hs6:161150567-161150567;hs8:75087899-75087899,hs8:75095377-75095377;hs11:1570862-1570862,hs11:1591488-1591488;hs11:12396199-12396199,hs11:65061640-65061640;hs11:17807056-17807056,hs11:28105191-28105191;hs11:17836821-17836821,hs11:28280080-28280080;hs11:18046070-18046070,hs11:28165047-28165047;hs11:18058151-18058151,hs11:18099512-18099512;hs11:18058423-18058423,hs11:28369161-28369161;hs11:18101635-18101635,hs11:20655414-20655414;hs11:18168973-18168973,hs11:28164502-28164502;hs11:18169076-18169076,hs11:28650047-28650047;hs11:69240671-69240671,hs15:86472754-86472754;hs11:85367580-85367580,hs11:85368252-85368252;hs11:85367591-85367591,hs11:85367851-85367851;hs11:113178251-113178251,hs15:86471229-86471229;hs21:46222881-46222881,hs22:24203554-24203554;hs22:43084148-43084148,hs22:43087160-43087160;hsX:10879936-10879936,hsX:107677238-107677238;hsX:10880027-10880027,hsX:107743206-107743206;hsX:10944804-10944804,hsX:107743234-107743234;hsX:10944950-10944950,hsX:107726147-107726147 COL4A5;COL4A6;CCND1 Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland BACKGROUND: Uterine leiomyomas are benign but affect the health of millions of women. A better understanding of the molecular mechanisms involved may provide clues to the prevention and treatment of these lesions. METHODS: We performed whole-genome sequencing and gene-expression profiling of 38 uterine leiomyomas and the corresponding myometrium from 30 women. RESULTS: Identical variants observed in some separate tumor nodules suggested that these nodules have a common origin. Complex chromosomal rearrangements resembling chromothripsis were a common feature of leiomyomas. These rearrangements are best explained by a single event of multiple chromosomal breaks and random reassembly. The rearrangements created tissue-specific changes consistent with a role in the initiation of leiomyoma, such as translocations of the HMGA2 and RAD51B loci and aberrations at the COL4A5-COL4A6 locus, and occurred in the presence of normal TP53 alleles. In some cases, separate events had occurred more than once in single tumor-cell lineages. CONCLUSIONS: Chromosome shattering and reassembly resembling chromothripsis (a single genomic event that results in focal losses and rearrangements in multiple genomic regions) is a major cause of chromosomal abnormalities in uterine leiomyomas; we propose that tumorigenesis occurs when tissue-specific tumor-promoting changes are formed through these events. Chromothripsis has previously been associated with aggressive cancer; its common occurrence in leiomyomas suggests that it also has a role in the genesis and progression of benign tumors. We observed that multiple separate tumors could be seeded from a single lineage of uterine leiomyoma cells. GRCh37/hg19 ERP004006 Yes COL4A5,COL4A6 CTDB0055 Research 23738515 Mehine M, Kaasinen E, Makinen N, Katainen R, Kampjarvi K, Pitkanen E, Heinonen HR, Butzow R, Kilpivaara O, Kuosmanen A, Ristolainen H, Gentile M, Sjoberg J, Vahteristo P, Aaltonen LA Characterization of Uterine Leiomyomas by Whole-Genome Sequencing N Engl J Med 2013 Jun 6,8,12,14 Uterine leiomyoma Next Generation Sequencing Homo sapiens MY64m1 Illumina + Complete Genomics hs1:15735163-15735163,hs3:194489954-194489954;hs1:194721032-194721032,hs1:196290033-196290033;hs1:215599195-215599195,hs1:215599663-215599663;hs3:33644813-33644813,hs19:12274466-12274466;hs3:49074459-49074459,hs10:80831180-80831180;hs3:52745459-52745459,hs22:39922071-39922071;hs3:180156793-180156793,hs3:180157535-180157535;hs3:194490234-194490234,hs3:194493153-194493153;hs4:6584525-6584525,hs4:34998329-34998329;hs6:1943008-1943008,hs6:2489341-2489341;hs6:11156592-11156592,hs7:84183676-84183676;hs6:31058593-31058593,hs6:31059135-31059135;hs6:53137916-53137916,hs6:53201720-53201720;hs6:53145310-53145310,hs6:53203374-53203374;hs6:66868428-66868428,hs6:66870032-66870032;hs6:70162245-70162245,hs6:99829857-99829857;hs6:70175391-70175391,hs6:99787202-99787202;hs6:76745802-76745802,hs6:76746261-76746261;hs6:81852454-81852454,hs6:128469968-128469968;hs6:88875408-88875408,hs12:25545729-25545729;hs6:109995770-109995770,hs6:109996343-109996343;hs6:112035549-112035549,hs6:113078054-113078054;hs6:112036919-112036919,hs6:113841690-113841690;hs6:112419542-112419542,hs6:114208063-114208063;hs6:131747203-131747203,hs6:131794379-131794379;hs7:83853697-83853697,hs7:83854456-83854456;hs7:112249350-112249350,hs7:113118707-113118707;hs7:112249511-112249511,hs7:113124180-113124180;hs7:113923991-113923991,hs7:113924617-113924617;hs7:117113777-117113777,hs7:117114825-117114825;hs7:122019607-122019607,hs7:122019982-122019982;hs7:136616071-136616071,hs7:136658639-136658639;hs7:148391040-148391040,hs7:148550062-148550062;hs8:93147079-93147079,hs8:94323704-94323704;hs8:93534914-93534914,hs6:88875071-88875071;hs8:93535474-93535474,hs12:92634896-92634896;hs8:93978876-93978876,hs14:89023605-89023605;hs11:24998979-24998979,hs11:25993614-25993614;hs12:25545779-25545779,hs12:48018996-48018996;hs12:65562575-65562575,hs8:93149069-93149069;hs12:66627402-66627402,hs12:66653581-66653581;hs12:92419990-92419990,hs12:92420090-92420090;hs12:92634041-92634041,hs14:93599917-93599917;hs14:68772909-68772909,hs12:65992890-65992890;hs14:68921193-68921193,hs12:67255815-67255815;hs14:97338363-97338363,hs14:97338802-97338802;hsX:83913042-83913042,hsX:98148639-98148639 RAD51B;HMGA2;CUL1;EZH2 Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland BACKGROUND: Uterine leiomyomas are benign but affect the health of millions of women. A better understanding of the molecular mechanisms involved may provide clues to the prevention and treatment of these lesions. METHODS: We performed whole-genome sequencing and gene-expression profiling of 38 uterine leiomyomas and the corresponding myometrium from 30 women. RESULTS: Identical variants observed in some separate tumor nodules suggested that these nodules have a common origin. Complex chromosomal rearrangements resembling chromothripsis were a common feature of leiomyomas. These rearrangements are best explained by a single event of multiple chromosomal breaks and random reassembly. The rearrangements created tissue-specific changes consistent with a role in the initiation of leiomyoma, such as translocations of the HMGA2 and RAD51B loci and aberrations at the COL4A5-COL4A6 locus, and occurred in the presence of normal TP53 alleles. In some cases, separate events had occurred more than once in single tumor-cell lineages. CONCLUSIONS: Chromosome shattering and reassembly resembling chromothripsis (a single genomic event that results in focal losses and rearrangements in multiple genomic regions) is a major cause of chromosomal abnormalities in uterine leiomyomas; we propose that tumorigenesis occurs when tissue-specific tumor-promoting changes are formed through these events. Chromothripsis has previously been associated with aggressive cancer; its common occurrence in leiomyomas suggests that it also has a role in the genesis and progression of benign tumors. We observed that multiple separate tumors could be seeded from a single lineage of uterine leiomyoma cells. GRCh37/hg19 ERP004006 Yes NA CTDB0056 Research 23738515 Mehine M, Kaasinen E, Makinen N, Katainen R, Kampjarvi K, Pitkanen E, Heinonen HR, Butzow R, Kilpivaara O, Kuosmanen A, Ristolainen H, Gentile M, Sjoberg J, Vahteristo P, Aaltonen LA Characterization of Uterine Leiomyomas by Whole-Genome Sequencing N Engl J Med 2013 Jun 1,5,14 Uterine leiomyoma Next Generation Sequencing Homo sapiens MY18m3 Illumina + Complete Genomics chr14:63744555-68216937:-1;chr19:27681783-141213431:-1;chr1:882685-29447281:-1;chr4:1-49660117:-1;chr5:149752077-158199892:-1 hs1:882685-882685,hs1:31085347-31085347;hs1:29447281-29447281,hs20:34130261-34130261;hs1:31085225-31085225,hs2:27270624-27270624;hs1:87129957-87129957,hs1:87131702-87131702;hs5:98538029-98538029,hs5:98780516-98780516;hs5:98774085-98774085,hs5:100605647-100605647;hs5:98780238-98780238,hs5:99577432-99577432;hs5:100534516-100534516,hs5:149570825-149570825;hs5:100607932-100607932,hs5:158551243-158551243;hs5:100611427-100611427,hs5:158199892-158199892;hs5:100881397-100881397,hs5:100882761-100882761;hs5:107392713-107392713,hs5:149752077-149752077;hs8:29056894-29056894,hs8:29049690-29049690;hs12:66200468-66200468,hs14:69025073-69025073;hs12:66336514-66336514,hs12:66336991-66336991;hs12:121190353-121190353,hs12:121190839-121190839;hs14:19162878-19162878,hs14:69524710-69524710;hs14:24720540-24720540,hs14:75769241-75769241;hs14:39424193-39424193,hs14:63744555-63744555;hs14:43740449-43740449,hs14:69021171-69021171;hs14:69020643-69020643,hs12:66201378-66201378;hs14:69025181-69025181,hs14:92959674-92959674;hs14:69524711-69524711,hs14:68216937-68216937;hs14:69624170-69624170,hs14:93149131-93149131;hs14:69624603-69624603,hs14:93160067-93160067;hs14:92957591-92957591,hs14:24720863-24720863;hs20:34130689-34130689,hs2:27316575-27316575 RAD51B;HMGA2 Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland BACKGROUND: Uterine leiomyomas are benign but affect the health of millions of women. A better understanding of the molecular mechanisms involved may provide clues to the prevention and treatment of these lesions. METHODS: We performed whole-genome sequencing and gene-expression profiling of 38 uterine leiomyomas and the corresponding myometrium from 30 women. RESULTS: Identical variants observed in some separate tumor nodules suggested that these nodules have a common origin. Complex chromosomal rearrangements resembling chromothripsis were a common feature of leiomyomas. These rearrangements are best explained by a single event of multiple chromosomal breaks and random reassembly. The rearrangements created tissue-specific changes consistent with a role in the initiation of leiomyoma, such as translocations of the HMGA2 and RAD51B loci and aberrations at the COL4A5-COL4A6 locus, and occurred in the presence of normal TP53 alleles. In some cases, separate events had occurred more than once in single tumor-cell lineages. CONCLUSIONS: Chromosome shattering and reassembly resembling chromothripsis (a single genomic event that results in focal losses and rearrangements in multiple genomic regions) is a major cause of chromosomal abnormalities in uterine leiomyomas; we propose that tumorigenesis occurs when tissue-specific tumor-promoting changes are formed through these events. Chromothripsis has previously been associated with aggressive cancer; its common occurrence in leiomyomas suggests that it also has a role in the genesis and progression of benign tumors. We observed that multiple separate tumors could be seeded from a single lineage of uterine leiomyoma cells. GRCh37/hg19 ERP004006 Yes RAD51B,HMGA2 CTDB0058 Research 24469795 Morrison CD, Liu P, Woloszynska-Read A, Zhang J, Luo W, Qin M, Bshara W, Conroy JM, Sabatini L, Vedell P, Xiong D, Liu S, Wang J, Shen H, Li Y, Omilian AR, Hill A, Head K, Guru K, Kunnev D, Leach R, Eng KH, Darlak C, Hoeflich C, Veeranki S, Glenn S, You M Whole-genome sequencing identifies genomic heterogeneity at a nucleotide and chromosomal level in bladder cancer PNAS 2014 Jan 4,5,6 Bladder cancer Next Generation Sequencing Homo sapiens 18195 Illumina HiSeq 2000 chr12:15868221-15869407:-1;chr13:25958271-25982948:-1;chr13:47357937-47895151:-1;chr13:50576609-51283899:-1;chr16:89347877-89355605:-1;chr17:15396178-15984150:-1;chr18:8064603-8079939:-1;chr2:141248335-141377828:-1;chr2:141682019-142033558:-1;chr2:141800301-141865698:-1;chr2:166207909-166746319:-1;chr2:212365974-212497679:-1;chr2:55702844-57945495:-1;chr2:76235801-76236576:-1;chr3:60647686-61150861:-1;chr4:143858104-150512751:-1;chr5:24639248-24829428:-1;chr7:51514678-51523200:-1;chr7:78339452-78352430:-1;chr9:13417895-14381409:-1 hs1:189182665-189182665,hs2:4522643-4522643;hs4:123484083-123484083,hs6:24118632-24118632;hs4:123561315-123561315,hs6:24122385-24122385;hs4:124664946-124664946,hs6:10407849-10407849;hs4:125115818-125115818,hs4:169013589-169013589;hs4:128690025-128690025,hs4:128690444-128690444;hs4:143860688-143860688,hs6:10407009-10407009;hs4:145338318-145338318,hs4:151076217-151076217;hs4:169007852-169007852,hs5:40050668-40050668;hs4:169014029-169014029,hs6:20697120-20697120;hs4:185413107-185413107,hs6:50112900-50112900;hs4:185717832-185717832,hs6:49786067-49786067;hs4:185720119-185720119,hs5:41232937-41232937;hs4:185727981-185727981,hs6:49787649-49787649;hs4:185879694-185879694,hs6:10408205-10408205;hs5:14499897-14499897,hs6:10400566-10400566;hs5:14503114-14503114,hs5:24902285-24902285;hs5:14511701-14511701,hs6:24347839-24347839;hs5:24625080-24625080,hs13:50006548-50006548;hs5:25237830-25237830,hs5:40040222-40040222;hs5:29690933-29690933,hs6:49784660-49784660;hs5:37251584-37251584,hs6:10424400-10424400;hs5:37295108-37295108,hs6:49782746-49782746;hs5:40062440-40062440,hs6:20736167-20736167;hs6:24325453-24325453,hs6:49597606-49597606;hs6:37516484-37516484,hs6:37530727-37530727;hs12:63150384-63150384,hs12:63602159-63602159;hs13:25957850-25957850,hs13:25961756-25961756;hs13:25963023-25963023,hs13:25984817-25984817 CDH10;CAB39L Center for Personalized Medicine and Departments of Pharmacology and Therapeutics, Cancer Genetics, Biostatistics and Bioinformatics, Pathology, Urology, Molecular and Cellular Biology, and Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263. Using complete genome analysis, we sequenced five bladder tumors accrued from patients with muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) and identified a spectrum of genomic aberrations. In three tumors, complex genotype changes were noted. All three had tumor protein p53 mutations and a relatively large number of single-nucleotide variants (SNVs; average of 11.2 per megabase), structural variants (SVs; average of 46), or both. This group was best characterized by chromothripsis and the presence of subclonal populations of neoplastic cells or intratumoral mutational heterogeneity. Here, we provide evidence that the process of chromothripsis in TCC-UB is mediated by nonhomologous end-joining using kilobase, rather than megabase, fragments of DNA, which we refer to as stitchers, to repair this process. We postulate that a potential unifying theme among tumors with the more complex genotype group is a defective replication-licensing complex. A second group (two bladdertumors) had no chromothripsis, and a simpler genotype, WT tumor protein p53, had relatively few SNVs (average of 5.9 per megabase) and only a single SV. There was no evidence of a subclonal population of neoplastic cells. In this group, we used a preclinical model of bladder carcinoma cell lines to study a unique SV (translocation and amplification) of the gene glutamate receptor ionotropic N-methyl D-aspertate as a potential new therapeutic target in ladder cancer. NCBI 36/hg18 ERP004006 Yes CDH10,CAB39L CTDB0059 Research 24469795 Morrison CD, Liu P, Woloszynska-Read A, Zhang J, Luo W, Qin M, Bshara W, Conroy JM, Sabatini L, Vedell P, Xiong D, Liu S, Wang J, Shen H, Li Y, Omilian AR, Hill A, Head K, Guru K, Kunnev D, Leach R, Eng KH, Darlak C, Hoeflich C, Veeranki S, Glenn S, You M Whole-genome sequencing identifies genomic heterogeneity at a nucleotide and chromosomal level in bladder cancer PNAS 2014 Jan 11,12,17 Bladder cancer Next Generation Sequencing Homo sapiens 18698 Illumina HiSeq 2000 chr11:66504877-68461658:-1;chr12:46214421-47093283:-1;chr17:36915522-37804427:-1;chr1:47231278-87529442:-1;chr9:21868718-24184888:-1 hs1:105326347-105326347,hs1:105326669-105326669;hs3:13593328-13593328,hs3:21559260-21559260;hs3:18242480-18242480,hs3:18256751-18256751;hs4:180787743-180787743,hs4:181469774-181469774;hs7:107728025-107728025,hs7:115159186-115159186;hs8:34012822-34012822,hs17:37894488-37894488;hs11:69603563-69603563,hs11:71258963-71258963;hs11:119315586-119315586,hs12:47939157-47939157;hs12:46210326-46210326,hs12:46211370-46211370;hs12:47797901-47797901,hs12:47801447-47801447;hs13:22319164-22319164,hs13:22331301-22331301;hs17:36656397-36656397,hs17:36658640-36658640;hs17:59424176-59424176,hs17:59623009-59623009;hs18:27135323-27135323,hs18:28064691-28064691;hs18:29094661-29094661,hs18:29095531-29095531 Center for Personalized Medicine and Departments of Pharmacology and Therapeutics, Cancer Genetics, Biostatistics and Bioinformatics, Pathology, Urology, Molecular and Cellular Biology, and Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263. Using complete genome analysis, we sequenced five bladder tumors accrued from patients with muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) and identified a spectrum of genomic aberrations. In three tumors, complex genotype changes were noted. All three had tumor protein p53 mutations and a relatively large number of single-nucleotide variants (SNVs; average of 11.2 per megabase), structural variants (SVs; average of 46), or both. This group was best characterized by chromothripsis and the presence of subclonal populations of neoplastic cells or intratumoral mutational heterogeneity. Here, we provide evidence that the process of chromothripsis in TCC-UB is mediated by nonhomologous end-joining using kilobase, rather than megabase, fragments of DNA, which we refer to as stitchers, to repair this process. We postulate that a potential unifying theme among tumors with the more complex genotype group is a defective replication-licensing complex. A second group (two bladdertumors) had no chromothripsis, and a simpler genotype, WT tumor protein p53, had relatively few SNVs (average of 5.9 per megabase) and only a single SV. There was no evidence of a subclonal population of neoplastic cells. In this group, we used a preclinical model of bladder carcinoma cell lines to study a unique SV (translocation and amplification) of the gene glutamate receptor ionotropic N-methyl D-aspertate as a potential new therapeutic target in ladder cancer. NCBI 36/hg18 Yes NA CTDB0060 Research 24469795 Morrison CD, Liu P, Woloszynska-Read A, Zhang J, Luo W, Qin M, Bshara W, Conroy JM, Sabatini L, Vedell P, Xiong D, Liu S, Wang J, Shen H, Li Y, Omilian AR, Hill A, Head K, Guru K, Kunnev D, Leach R, Eng KH, Darlak C, Hoeflich C, Veeranki S, Glenn S, You M Whole-genome sequencing identifies genomic heterogeneity at a nucleotide and chromosomal level in bladder cancer PNAS 2014 Jan 2,4,5,6,10,18,19 Bladder cancer Next Generation Sequencing Homo sapiens 19685 Illumina HiSeq 2000 chr13:21067952-42227057:-1;chr13:46269197-70851443:-1;chr14:102894735-102918992:-1;chr14:41437002-41437905:-1;chr15:89778081-89851425:-1;chr17:47113498-47114554:-1;chr19:14031700-16386190:-1;chr19:14038991-14211307:-1;chr19:18740629-19009858:-1;chr19:28721949-31837160:-1;chr21:27419049-30352374:-1;chr21:27494111-31693492:-1;chr2:142808431-142817549:-1;chr2:194004736-201221178:-1;chr2:62687819-97678586:-1;chr4:19934716-19936610:-1;chr4:81774226-87306782:-1;chr4:87310129-99601329:-1;chr5:142492704-142543234:-1;chr5:31171782-31261268:-1;chr5:33835925-33841123:-1;chr5:61432448-160401023:-1;chr5:62106393-140375046:-1;chr6:20062895-20063651:-1;chr6:49699773-49701405:-1;chr6:62545122-66578795:-1;chr7:120306456-120308862:-1;chr7:44924241-46068829:-1;chr8:140348207-140367209:-1;chr8:141005164-141024666:-1;chr9:89734221-89750048:-1;chrX:24535818-24536939:-1 hs2:74496729-74496729,hs2:88536586-88536586;hs2:84278098-84278098,hs13:74531816-74531816;hs2:177602102-177602102,hs2:180425416-180425416;hs2:177850934-177850934,hs4:134021859-134021859;hs3:2231340-2231340,hs5:163882786-163882786;hs3:2239599-2239599,hs21:31420630-31420630;hs3:2271739-2271739,hs5:163488040-163488040;hs4:80876697-80876697,hs4:90969695-90969695;hs4:88965722-88965722,hs5:159136178-159136178;hs4:90784690-90784690,hs4:111017791-111017791;hs4:98230738-98230738,hs4:98298792-98298792;hs4:110318503-110318503,hs4:115783941-115783941;hs4:114352224-114352224,hs5:53118673-53118673;hs4:117358105-117358105,hs4:118357230-118357230;hs4:137613428-137613428,hs4:139064982-139064982;hs4:179409744-179409744,hs4:183350902-183350902;hs4:190851149-190851149,hs4:190852682-190852682;hs4:190864028-190864028,hs4:190864840-190864840;hs5:29794592-29794592,hs5:39986499-39986499;hs5:44712327-44712327,hs22:44760032-44760032;hs5:159938168-159938168,hs5:159939342-159939342;hs5:163482561-163482561,hs21:30411608-30411608;hs5:163862906-163862906,hs21:31057408-31057408;hs5:163930283-163930283,hs21:14760263-14760263;hs6:38642057-38642057,hs6:123531219-123531219;hs6:95495247-95495247,hs6:95507186-95507186;hs6:123664417-123664417,hs6:168228563-168228563;hs7:39122539-39122539,hs7:43488983-43488983;hs7:51782883-51782883,hs14:49749698-49749698;hs8:54044492-54044492,hs8:54056801-54056801;hs10:14590169-14590169,hs10:17339901-17339901;hs10:14920218-14920218,hs10:19462426-19462426;hs10:20488666-20488666,hs10:82241782-82241782;hs10:77971215-77971215,hs10:77972984-77972984;hs10:81226556-81226556,hs10:81227461-81227461;hs10:82529858-82529858,hs10:82531949-82531949;hs11:6055332-6055332,hs11:30222215-30222215;hs11:39205130-39205130,hs11:46336487-46336487;hs13:25465821-25465821,hs13:25482780-25482780;hs16:33611973-33611973,hs16:33614235-33614235;hs18:24946647-24946647,hs18:24946982-24946982;hs18:26240178-26240178,hs18:57422314-57422314;hs18:34109579-34109579,hs18:58799580-58799580;hs18:57416350-57416350,hs18:58358748-58358748;hs19:17136916-17136916,hs19:17348961-17348961;hs19:46716153-46716153,hs19:50384324-50384324;hs20:44543514-44543514,hs20:44545696-44545696 Center for Personalized Medicine and Departments of Pharmacology and Therapeutics, Cancer Genetics, Biostatistics and Bioinformatics, Pathology, Urology, Molecular and Cellular Biology, and Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263. Using complete genome analysis, we sequenced five bladder tumors accrued from patients with muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) and identified a spectrum of genomic aberrations. In three tumors, complex genotype changes were noted. All three had tumor protein p53 mutations and a relatively large number of single-nucleotide variants (SNVs; average of 11.2 per megabase), structural variants (SVs; average of 46), or both. This group was best characterized by chromothripsis and the presence of subclonal populations of neoplastic cells or intratumoral mutational heterogeneity. Here, we provide evidence that the process of chromothripsis in TCC-UB is mediated by nonhomologous end-joining using kilobase, rather than megabase, fragments of DNA, which we refer to as stitchers, to repair this process. We postulate that a potential unifying theme among tumors with the more complex genotype group is a defective replication-licensing complex. A second group (two bladdertumors) had no chromothripsis, and a simpler genotype, WT tumor protein p53, had relatively few SNVs (average of 5.9 per megabase) and only a single SV. There was no evidence of a subclonal population of neoplastic cells. In this group, we used a preclinical model of bladder carcinoma cell lines to study a unique SV (translocation and amplification) of the gene glutamate receptor ionotropic N-methyl D-aspertate as a potential new therapeutic target in ladder cancer. NCBI 36/hg18 Yes NA CTDB0061 Research 25799107 de Pagter MS, van Roosmalen MJ, Baas AF, Renkens I, Duran KJ, van Binsbergen E, Tavakoli-Yaraki M, Hochstenbach R, van der Veken LT, Cuppen E, Kloosterman WP Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring Am J Hum Genet 2015 Apr 9,10,14,16 Congenital abnormality Next Generation Sequencing Homo sapiens Mother1 AB SOLiD 4 System hs9:10640282-10641388,hg9:12067163-12069048;hs10:85708440-85709723,hs16:62811907-62813013;hs9:10643066-10645130,hs14:87959160-87960589;hs9:9874447-9875887,hs9:10397725-10400216;hs9:9877636-9880121,hs9:10184962-10187413;hs16:62814654-62819507,hs16:62837225-62840110;hs9:9039041-9043602,hs9:12069501-12073773;hs9:633474-636448,hs9:9043966-9046015;hs9:9043986-9045832,hs10:84550840-84554624;hs10:85704055-85707766,hs16:62832514-62837165;hs14:87956251-87957402,hs9:630972-632755;hs10:84549834-84549834,hs9:9048033-9048033;hs9:10182312-10184604,hs9:10400974-10404035 PTPRD;KANK1;NRG3 Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht 3584 CG, the Netherlands Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across three to five chromosomes. Two mothers did not show any phenotypic abnormalities, although 3-13 protein-coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy-number changes in two children. This resulted in gene-dosage changes, which are probably responsible for the severe congenital phenotypes of these two children. In contrast, the third child, who has a severe congenital disease, harbored all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy-number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein-coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals affects reproduction and is expected to substantially increase the risk of miscarriages, abortions, and severe congenital disease. GRCh37/hg19 GSE65454 No NA CTDB0062 Research 25799107 de Pagter MS, van Roosmalen MJ, Baas AF, Renkens I, Duran KJ, van Binsbergen E, Tavakoli-Yaraki M, Hochstenbach R, van der Veken LT, Cuppen E, Kloosterman WP Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring Am J Hum Genet 2015 Apr 6,7,9,10,12 Congenital abnormality Next Generation Sequencing Homo sapiens Mother2 AB SOLiD 4 System hs7:36718108-36721671,hs12:99787831-99790893;hs9:11739802-11742710,hs9:31460247-31463007;hs9:11758195-11759972,hs12:110263742-110266538;hs9:7104763-7106960,hs12:103464346-103466774;hs9:12236188-12238989,hs9:26965673-26968013;hs9:13236665-13239425,hs12:101859464-101861141;hs6:123750357-123752276,hs9:11743072-11746336;hs6:123765872-123766384,hs12:101856510-101856537;hs9:31433337-31436333,hs9:31463517-31465231;hs9:31471300-31473229,hs12:99435218-99436825;hs6:123748945-123750012,hs6:123768304-123769906;hs10:66227201-66230197,hs12:99785257-99787355;hs9:8118030-8119888,hs10:65848657-65850658;hs7:36714976-36717979,hs12:103467238-103470137;hs9:7107641-7109780,hs9:35723601-35726283;hs9:13334672-13337076,hs9:31473792-31476201;hs9:13240004-13241557,hs9:26962041-26964677;hs9:7116561-7120299,hs9:31436447-31440029;hs9:8121313-8122780,hs9:11760865-11763707;hs9:12233990-12236078,hs12:99431406-99434124;hs9:7113602-7116395,hs12:110267135-110269429;hs9:13337440-13340068,hs12:99636114-99638904;hs10:65844061-65847557,hs10:66230913-66234003;hs12:99634461-99634461,hs9:35727377-35727377 AOAH;ANKS1B;TRPV4;KDM4C;MPDZ;IFT74;TRDN;TLN1;CREB3 Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht 3584 CG, the Netherlands Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across three to five chromosomes. Two mothers did not show any phenotypic abnormalities, although 3-13 protein-coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy-number changes in two children. This resulted in gene-dosage changes, which are probably responsible for the severe congenital phenotypes of these two children. In contrast, the third child, who has a severe congenital disease, harbored all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy-number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein-coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals affects reproduction and is expected to substantially increase the risk of miscarriages, abortions, and severe congenital disease. GRCh37/hg19 GSE65454 No NA CTDB0063 Research 25799107 de Pagter MS, van Roosmalen MJ, Baas AF, Renkens I, Duran KJ, van Binsbergen E, Tavakoli-Yaraki M, Hochstenbach R, van der Veken LT, Cuppen E, Kloosterman WP Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring Am J Hum Genet 2015 Apr 1,3,5 Congenital abnormality Next Generation Sequencing Homo sapiens Mother3 AB SOLiD 4 System hs3:158384939-158388876,hs3:195632595-195635632;hs1:154441965-154444308,hs3:195630328-195631725;hs1:154445895-154448216,hs3:156530510-156533437;hs1:153155549-153158347,hs5:29436496-29438223;hs1:151021102-151023743,hs5:29433067-29436167;hs3:128911732-128913422,hs3:156534632-156536932;hs1:153746565-153748730,hs3:158389428-158392531;hs1:151018679-151020295,hs1:153151785-153154013 GFM1;LXN;TNK2;SHE;IL6R;C1orf56;BNIPL;CDC42SE1;MLLT11;LEKR1;PA2G4P4;SLC27A3;INTS3 Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht 3584 CG, the Netherlands Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across three to five chromosomes. Two mothers did not show any phenotypic abnormalities, although 3-13 protein-coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy-number changes in two children. This resulted in gene-dosage changes, which are probably responsible for the severe congenital phenotypes of these two children. In contrast, the third child, who has a severe congenital disease, harbored all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy-number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein-coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals affects reproduction and is expected to substantially increase the risk of miscarriages, abortions, and severe congenital disease. GRCh37/hg19 GSE65454 No NA CTDB0064 Research 25662009 McDermott DH, Gao JL, Liu Q, Siwicki M, Martens C, Jacobs P, Velez D, Yim E, Bryke CR, Hsu N, Dai Z, Marquesen MM, Stregevsky E, Kwatemaa N, Theobald N, Long Priel DA, Pittaluga S, Raffeld MA, Calvo KR, Maric I, Desmond R, Holmes KL, Kuhns DB, Balabanian Chromothriptic cure of WHIM syndrome Cell 2015 Feb 2 WHIM syndrome Next Generation Sequencing Homo sapiens WHIM-09 Illumina HiSeq 2000 chr2:9500000-22000000:-1;chr2:24000000-26000000:-1;chr2:102000000-106000000:-1;chr2:132000000-133500000:-1;chr2:134000000-137000000:-1;chr2:155000000-157000000:-1;chr2:158000000-165000000:-1 hs2:9650469-9650469,hs2:92323543-92323543,HH;hs2:26227289-26227289,hs2:102167978-102167978,TT;hs2:102168450-102168450,hs2:156704625-156704625,HT;hs2:157479872-157479872,hs2:134383040-134383040,HH;hs2:134379440-134379440,hs2:18013669-18013669,TT;hs2:18014058-18014058,hs2:137413687-137413687,HH;hs2:137402471-137402471,hs2:155186295-155186295,TH;hs2:137413696-137413696,hs2:134383068-134383068,TT;hs2:134384129-134384129,hs2:134208472-134208472,HH;hs2:133712996-133712996,hs2:132361705-132361705,TH;hs2:106220579-106220579,hs2:24238501-24238501,TH;hs2:22647206-22647206,hs2:137344145-137344145,TT;hs2:137350425-137350425,hs2:92314297-92314297,HT;hs2:102176282-102176282,hs2:13364053-13364053,HH;hs2:13332820-13332820,hs2:133689046-133689046,TT;hs2:133712975-133712975,hs2:134248797-134248797,HH;hs2:134208529-134208529,hs2:164835205-164835205,TT ACMSD;ACVR1;ACVR1C;ADAM17;ADCY3;ANKRD30BL;APOB;ASXL2;ATP6V1C2;BAZ2B;C2orf27A;C2orf27B;C2orf43;C2orf44;C2orf48;C2orf49;C2orf50;C2orf84;CCDC148;CCNT2;CD302;CENPO;CXCR4;CYS1;CYTIP;DAPL1;DARS;DDX1;DNAJC27;DNAJC27-AS1;DNMT3A;DPP4;DTNB;E2F6;EFR3B;ERMN;FAM49A;FAM84A;FAP;FHL2;FIGN;FKBP1B;FLJ12334;FLJ33534;GALNT13;GALNT5;GCA;GCG;GDF7;GEN1;GPR39;GPR45;GREB1;GRHL1;HPCAL1;HS1BP3;IFIH1;IL18R1;IL18RAP;IL1R1;IL1R2;IL1RL1;IL1RL2;ITGB6;ITSN2;KCNF1;KCNH7;KCNJ3;KCNS3;KIF3C;KLF11;LAPTM4A;LCT;LOC100129961;LOC100144595;LOC100287010;LOC100506421;LOC100506474;LOC100507600;LOC150568;LOC284998;LOC285000;LOC375190;LOC554201;LOC645949;LPIN1;LY75;LY75-CD302;LYPD1;MAP4K4;MARCH7;MATN3;MCM6;MFSD2B;MFSD9;MGAT5;MIR128-1;MIR1301;MIR3125;MIR3679;MIR4261;MIR4262;MIR4429;MIR4757;MIR4772;MIR4785;MIR663B;MRPS9;MSGN1;MYCN;MYCNOS;NBAS;NCKAP5;NCOA1;NOL10;NT5C1B;NT5C1B-RDH14;NTSR2;ODC1;OSR1;PDIA6;PFN4;PKP4;PLA2R1;POMC;POTEKP;POU3F3;PQLC3;PSMD14;PTRHD1;PUM2;R3HDM1;RAB3GAP1;RAD51AP2;RBMS1;RDH14;RHOB;ROCK2;RRM2;SDC1;SF3B14;SLC4A10;SLC9A2;SLC9A4;SMC6;SNORA80B;TAF1B;TANC1;TANK;TBR1;TGFBRAP1;TMEM163;TMEM182;TP53I3;TRIB2;TTC32;UBXN4;UPP2;VSNL1;WDR35;WDSUB1;YSK4;YWHAQ;ZRANB3 Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA Chromothripsis is a catastrophic cellular event recently described in cancer in which chromosomes undergo massive deletion and rearrangement. Here, we report a case in which chromothripsis spontaneously cured a patient with WHIM syndrome, an autosomal dominant combined immunodeficiency disease caused by gain-of-function mutation of the chemokine receptor CXCR4. In this patient, deletion of the disease allele, CXCR4(R334X), as well as 163 other genes from one copy of chromosome 2 occurred in a hematopoietic stem cell (HSC) that repopulated the myeloid but not the lymphoid lineage. In competitive mouse bone marrow (BM) transplantation experiments, Cxcr4 haploinsufficiency was sufficient to confer a strong long-term engraftment advantage of donor BM over BM from either wild-type or WHIM syndrome model mice, suggesting a potential mechanism for the patient's cure. Our findings suggest that partial inactivation of CXCR4 may have general utility as a strategy to promote HSC engraftment in transplantation. GRCh37/hg19 No MFSD2B,LOC258000;POTEKP,NCKAP5 CTDB0065 Research 25517748 Garsed DW, Marshall OJ, Corbin VD, Hsu A, Di Stefano L, Schroder J, Li J, Feng ZP, Kim BW, Kowarsky M, Lansdell B, Brookwell R, Myklebost O, Meza-Zepeda L, Holloway AJ, Pedeutour F, Choo KH, Damore MA, Deans AJ, Papenfuss AT, Thomas DM The Architecture and Evolution of Cancer Neochromosomes Cancer Cell 2014 Nov 1,4,5,7,9,10,12,13,15,16,20,21,22 Liposarcoma Next Generation Sequencing Homo sapiens 778 Illumina HiSeq 2000 Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia We isolated and analyzed, at single-nucleotide resolution, cancer-associated neochromosomes from well- and/or dedifferentiated liposarcomas. Neochromosomes, which can exceed 600 Mb in size, initially arise as circular structures following chromothripsis involving chromosome 12. The core of the neochromosome is amplified, rearranged, and corroded through hundreds of breakage-fusion-bridge cycles. Under selective pressure, amplified oncogenes are overexpressed, while coamplified passenger genes may be silenced epigenetically. New material may be captured during punctuated chromothriptic events. Centromeric corrosion leads to crisis, which is resolved through neocentromere formation or native centromere capture. Finally, amplification terminates, and the neochromosome core is stabilized in linear form by telomere capture. This study investigates the dynamic mutational processes underlying the life history of a special form of cancer mutation. GRCh37/hg19 Yes YEATS4,TAF3 CTDB0066 Research 25517748 Garsed DW, Marshall OJ, Corbin VD, Hsu A, Di Stefano L, Schroder J, Li J, Feng ZP, Kim BW, Kowarsky M, Lansdell B, Brookwell R, Myklebost O, Meza-Zepeda L, Holloway AJ, Pedeutour F, Choo KH, Damore MA, Deans AJ, Papenfuss AT, Thomas DM The Architecture and Evolution of Cancer Neochromosomes Cancer Cell 2014 Nov 1,4,5,9,10,12,13,15,16,20,21 Liposarcoma Next Generation Sequencing Homo sapiens 449 Illumina HiSeq 2000 Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia We isolated and analyzed, at single-nucleotide resolution, cancer-associated neochromosomes from well- and/or dedifferentiated liposarcomas. Neochromosomes, which can exceed 600 Mb in size, initially arise as circular structures following chromothripsis involving chromosome 12. The core of the neochromosome is amplified, rearranged, and corroded through hundreds of breakage-fusion-bridge cycles. Under selective pressure, amplified oncogenes are overexpressed, while coamplified passenger genes may be silenced epigenetically. New material may be captured during punctuated chromothriptic events. Centromeric corrosion leads to crisis, which is resolved through neocentromere formation or native centromere capture. Finally, amplification terminates, and the neochromosome core is stabilized in linear form by telomere capture. This study investigates the dynamic mutational processes underlying the life history of a special form of cancer mutation. GRCh37/hg19 Yes NA CTDB0067 Research 25517748 Garsed DW, Marshall OJ, Corbin VD, Hsu A, Di Stefano L, Schroder J, Li J, Feng ZP, Kim BW, Kowarsky M, Lansdell B, Brookwell R, Myklebost O, Meza-Zepeda L, Holloway AJ, Pedeutour F, Choo KH, Damore MA, Deans AJ, Papenfuss AT, Thomas DM The Architecture and Evolution of Cancer Neochromosomes Cancer Cell 2014 Nov 1,12,13,X Liposarcoma Next Generation Sequencing Homo sapiens GOT3 Illumina HiSeq 2000 Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia We isolated and analyzed, at single-nucleotide resolution, cancer-associated neochromosomes from well- and/or dedifferentiated liposarcomas. Neochromosomes, which can exceed 600 Mb in size, initially arise as circular structures following chromothripsis involving chromosome 12. The core of the neochromosome is amplified, rearranged, and corroded through hundreds of breakage-fusion-bridge cycles. Under selective pressure, amplified oncogenes are overexpressed, while coamplified passenger genes may be silenced epigenetically. New material may be captured during punctuated chromothriptic events. Centromeric corrosion leads to crisis, which is resolved through neocentromere formation or native centromere capture. Finally, amplification terminates, and the neochromosome core is stabilized in linear form by telomere capture. This study investigates the dynamic mutational processes underlying the life history of a special form of cancer mutation. GRCh37/hg19 Yes NA CTDB0068 Research 25517748 Garsed DW, Marshall OJ, Corbin VD, Hsu A, Di Stefano L, Schroder J, Li J, Feng ZP, Kim BW, Kowarsky M, Lansdell B, Brookwell R, Myklebost O, Meza-Zepeda L, Holloway AJ, Pedeutour F, Choo KH, Damore MA, Deans AJ, Papenfuss AT, Thomas DM The Architecture and Evolution of Cancer Neochromosomes Cancer Cell 2014 Nov 2,10,12 Liposarcoma Next Generation Sequencing Homo sapiens T1000 Illumina HiSeq 2000 Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia We isolated and analyzed, at single-nucleotide resolution, cancer-associated neochromosomes from well- and/or dedifferentiated liposarcomas. Neochromosomes, which can exceed 600 Mb in size, initially arise as circular structures following chromothripsis involving chromosome 12. The core of the neochromosome is amplified, rearranged, and corroded through hundreds of breakage-fusion-bridge cycles. Under selective pressure, amplified oncogenes are overexpressed, while coamplified passenger genes may be silenced epigenetically. New material may be captured during punctuated chromothriptic events. Centromeric corrosion leads to crisis, which is resolved through neocentromere formation or native centromere capture. Finally, amplification terminates, and the neochromosome core is stabilized in linear form by telomere capture. This study investigates the dynamic mutational processes underlying the life history of a special form of cancer mutation. GRCh37/hg19 Yes NA CTDB0069 Research 25517748 Garsed DW, Marshall OJ, Corbin VD, Hsu A, Di Stefano L, Schroder J, Li J, Feng ZP, Kim BW, Kowarsky M, Lansdell B, Brookwell R, Myklebost O, Meza-Zepeda L, Holloway AJ, Pedeutour F, Choo KH, Damore MA, Deans AJ, Papenfuss AT, Thomas DM The Architecture and Evolution of Cancer Neochromosomes Cancer Cell 2014 Nov 1,2,3,5,7,8,9,12,14,15 Liposarcoma Next Generation Sequencing Homo sapiens LPS141 Illumina HiSeq 2000 Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia We isolated and analyzed, at single-nucleotide resolution, cancer-associated neochromosomes from well- and/or dedifferentiated liposarcomas. Neochromosomes, which can exceed 600 Mb in size, initially arise as circular structures following chromothripsis involving chromosome 12. The core of the neochromosome is amplified, rearranged, and corroded through hundreds of breakage-fusion-bridge cycles. Under selective pressure, amplified oncogenes are overexpressed, while coamplified passenger genes may be silenced epigenetically. New material may be captured during punctuated chromothriptic events. Centromeric corrosion leads to crisis, which is resolved through neocentromere formation or native centromere capture. Finally, amplification terminates, and the neochromosome core is stabilized in linear form by telomere capture. This study investigates the dynamic mutational processes underlying the life history of a special form of cancer mutation. GRCh37/hg19 Yes NA CTDB0070 Research 25517748 Garsed DW, Marshall OJ, Corbin VD, Hsu A, Di Stefano L, Schroder J, Li J, Feng ZP, Kim BW, Kowarsky M, Lansdell B, Brookwell R, Myklebost O, Meza-Zepeda L, Holloway AJ, Pedeutour F, Choo KH, Damore MA, Deans AJ, Papenfuss AT, Thomas DM The Architecture and Evolution of Cancer Neochromosomes Cancer Cell 2014 Nov 9,12 Liposarcoma Next Generation Sequencing Homo sapiens ST059 Illumina HiSeq 2000 Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia We isolated and analyzed, at single-nucleotide resolution, cancer-associated neochromosomes from well- and/or dedifferentiated liposarcomas. Neochromosomes, which can exceed 600 Mb in size, initially arise as circular structures following chromothripsis involving chromosome 12. The core of the neochromosome is amplified, rearranged, and corroded through hundreds of breakage-fusion-bridge cycles. Under selective pressure, amplified oncogenes are overexpressed, while coamplified passenger genes may be silenced epigenetically. New material may be captured during punctuated chromothriptic events. Centromeric corrosion leads to crisis, which is resolved through neocentromere formation or native centromere capture. Finally, amplification terminates, and the neochromosome core is stabilized in linear form by telomere capture. This study investigates the dynamic mutational processes underlying the life history of a special form of cancer mutation. GRCh37/hg19 Yes NA CTDB0071 Research 25517748 Garsed DW, Marshall OJ, Corbin VD, Hsu A, Di Stefano L, Schroder J, Li J, Feng ZP, Kim BW, Kowarsky M, Lansdell B, Brookwell R, Myklebost O, Meza-Zepeda L, Holloway AJ, Pedeutour F, Choo KH, Damore MA, Deans AJ, Papenfuss AT, Thomas DM The Architecture and Evolution of Cancer Neochromosomes Cancer Cell 2014 Nov 12 Liposarcoma Next Generation Sequencing Homo sapiens ST079 Illumina HiSeq 2000 Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia We isolated and analyzed, at single-nucleotide resolution, cancer-associated neochromosomes from well- and/or dedifferentiated liposarcomas. Neochromosomes, which can exceed 600 Mb in size, initially arise as circular structures following chromothripsis involving chromosome 12. The core of the neochromosome is amplified, rearranged, and corroded through hundreds of breakage-fusion-bridge cycles. Under selective pressure, amplified oncogenes are overexpressed, while coamplified passenger genes may be silenced epigenetically. New material may be captured during punctuated chromothriptic events. Centromeric corrosion leads to crisis, which is resolved through neocentromere formation or native centromere capture. Finally, amplification terminates, and the neochromosome core is stabilized in linear form by telomere capture. This study investigates the dynamic mutational processes underlying the life history of a special form of cancer mutation. GRCh37/hg19 Yes NA CTDB0077 Research 25545346 Flynn A, Benn D, Clifton-Bligh R, Robinson B, Trainer AH, James P, Hogg A, Waldeck K, George J, Li J, Fox SB, Gill AJ, McArthur G, Hicks RJ, Tothill RW. The genomic landscape of phaeochromocytoma. J Pathol 2015 May 11 Pheochromocytomas and paragangliomas Next Generation Sequencing Homo sapiens VCB02 Illumina HiSeq 2000 chr14:106073266-106536937:1;chr16:32843707-33814986:1;chr16:34440466-34755821:1;chr3:47685582-47872388:-1;chr11:98991024-99161979:-1;chr11:96533199-96762477:-1;chr11:95608563-95930305:-1;chr11:94508023-94620805:-1;chr11:94307510-94470779:-1;chr11:91797259-92155444:-1;chr11:9367219-10284338:-1;chr11:89776112-90024424:-1;chr11:88352253-89082537:-1;chr11:87583591-88289050:-1;chr11:87002361-87233478:-1;chr11:86345604-86675077:-1;chr11:85511021-86119818:-1;chr11:84890976-85330346:-1;chr11:84541817-84859310:-1;chr11:83416225-83537533:-1;chr11:82618413-82876242:-1;chr11:80420032-80813781:-1;chr11:8821443-9093570:-1;chr11:78267489-78438566:-1;chr11:77703696-77971664:-1;chr11:77064365-77691641:-1;chr11:76332168-76906676:-1;chr11:76016990-76326128:-1;chr11:75101844-75387629:-1;chr11:72882191-73393921:-1;chr11:71623012-72056717:-1;chr11:7463828-7804974:-1;chr11:69352173-69685706:-1;chr11:66183168-66518052:-1;chr11:62963964-63663990:-1;chr11:60593122-60974801:-1;chr11:6933054-7185996:-1;chr11:6435737-6649461:-1;chr11:55206501-55523703:-1;chr11:55069587-55197997:-1;chr11:50170917-50540673:-1;chr11:5211480-5537779:-1;chr11:49760742-50140507:-1;chr11:49106326-49447432:-1;chr11:47627919-47857470:-1;chr11:44274374-44448702:-1;chr11:43934914-44038206:-1;chr11:41696445-41903840:-1;chr11:41074754-41640927:-1;chr11:4168971-4605342:-1;chr11:39951150-40153990:-1;chr11:39468320-39783916:-1;chr11:38858882-39223893:-1;chr11:37909219-38828813:-1;chr11:36962252-37150275:-1;chr11:36545392-36799259:-1;chr11:35233704-35482228:-1;chr11:34492845-34892554:-1;chr11:33809471-33949500:-1;chr11:32688176-33049125:-1;chr11:32394861-32517997:-1;chr11:31725783-31818527:-1;chr11:30156932-30325711:-1;chr11:28785168-29567555:-1;chr11:28010301-28478523:-1;chr11:27710179-27970772:-1;chr11:25707061-26794036:-1;chr11:24135915-24462793:-1;chr11:23410862-23549584:-1;chr11:22777357-23389992:-1;chr11:21555509-21791071:-1;chr11:2650148-2933291:-1;chr11:17642611-18357493:-1;chr11:16243002-17578752:-1;chr11:15472498-15827879:-1;chr11:14594787-15204006:-1;chr11:134437948-134926782:-1;chr11:133071873-133246375:-1;chr11:132105242-132545127:-1;chr11:130733003-131076450:-1;chr11:13819290-14010113:-1;chr11:129654440-130335492:-1;chr11:128683914-128944858:-1;chr11:128339223-128598913:-1;chr11:128123675-128333668:-1;chr11:127405476-127711014:-1;chr11:126506756-126657319:-1;chr11:124752782-125485272:-1;chr11:123569106-123745280:-1;chr11:122925150-123310144:-1;chr11:122425497-122597421:-1;chr11:120880908-121286023:-1;chr11:120164785-120796581:-1;chr11:119720167-119923765:-1;chr11:118817151-119069474:-1;chr11:118459669-118693577:-1;chr11:118340500-118398791:-1;chr11:117458359-118135597:-1;chr11:116338431-116733451:-1;chr11:114695697-116321333:-1;chr11:114098413-114409606:-1;chr11:111769372-111988453:-1;chr11:111099717-111325362:-1;chr11:110864603-111041161:-1;chr11:109509515-109746772:-1;chr11:104114588-104696235:-1;chr11:102496184-102700504:-1;chr11:10522089-10694873:-1;chr11:1624627-1958705:-1 ADRBK1;ALDH3B2;AMBRA1;AMPD3;AP2A2;ARCN1;ARHGAP42;BARX2;C11orf49;C11orf75;C2CD3;CAPN1;CARS;CD44;COPB1;CTC-497E21.5;CTD-2313N18.2;CTD-2560E9.3;CTNND1;CWF19L2;DAGLA;DENND5A;FAT3;FCHSD2;GALNTL4;GRIK4;HYLS1;KIRREL3;LDHAL6A;LDLRAD3;MADD;NELL1;NOX4;PACS1;PDE2A;POLR2G;PSMD13;PUS3;RAB6A;RP11-295K3.1;RP11-406D1.2;RP11-563P16.1;RP11-660M18.2;RP11-676M6.1;RP11-770J1.3;RP5-1027O15.2;SLC22A18;SPCS2;SPI1;TEAD1;TRAF6 The Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; The Department of Pathology, University of Melbourne, Parkville, VIC, Australia Phaeochromocytomas (PCCs) and paragangliomas (PGLs) are rare neural crest-derived tumours originating from adrenal chromaffin cells or extra-adrenal sympathetic and parasympathetic tissues. More than a third of PCC/PGL cases are associated with heritable syndromes involving 13 or more known genes. These genes have been broadly partitioned into two groups based on pseudo-hypoxic and receptor tyrosine kinase (RTK) signalling pathways. Many of these genes can also become somatically mutated, although up to one third of sporadic cases have no known genetic driver. Furthermore, little is known of the genes that co-operate with known driver genes to initiate and drive tumourigenesis. To explore the genomic landscape of PCC/PGL, we applied exome sequencing, high-density SNP-array analysis, and RNA sequencing to 36 PCCs and four functional PGL tumours. All tumours displayed low mutation frequency, in contrast to frequent large segmental copy-number alterations, aneuploidy, and evidence for chromothripsis in one case. Multi-region sampling of one benign familial PCC tumour provided evidence for the timing of mutations during tumourigenesis and ongoing clonal evolution. Thirty-one of 40 (77.5%) cases could be explained by germline or somatic mutations or structural alterations affecting known PCC/PGL genes. Deleterious somatic mutations were also identified in known tumour-suppressor genes associated with genome maintenance and epigenetic modulation. A multitude of other genes were also found mutated that are likely important for normal neuroendocrine cell function. We revisited the gene-expression subtyping of PCC/PGL by integrating published microarray data with our RNA-seq data, enabling the identification of six robust gene-expression subtypes. The majority of cases in our cohort with no identifiable driver mutation were classified into a gene-expression subtype bearing similarity to MAX mutant PCC/PGL. Our data suggest there are yet unknown PCC/PGL cancer genes that can phenocopy MAX mutant PCC/PGL tumours. This study provides new insight into the molecular diversity and genetic origins of PCC/PGL tumours. GRCh37/hg19 GSE61594 Yes ADRBK1,TEAD1;AMBRA1,LDHAL6A;AMPD3,C11orf49;AP2A2,CTC-497E21.5;ARCN1,SLC22A18;C11orf49,AMPD3;C11orf75,RP11-660M18.2;CAPN1,SPI1;CARS,RP11-563P16.1;CD44,ARHGAP42;CD44,HYLS1;CD44,PUS3;COPB1,C2CD3;CWF19L2,RP11-676M6.1;CWF19L2,RP11-770J1.3;DAGLA,DENND5A;DENND5A,TRAF6;FAT3,GALNTL4;FCHSD2,CTD-2313N18.2;GRIK4,CTD-2560E9.3;MADD,NOX4;NELL1,BARX2;NOX4,LDLRAD3;PACS1,KIRREL3;PDE2A,ALDH3B2;PSMD13,SPCS2;RAB6A,RP5-1027O15.2;RP11-295K3.1,CTNND1;RP11-406D1.2,POLR2G CTDB0090 Research 25764012 Prabowo AS, van Thuijl HF, Scheinin I, Sie D, van Essen HF, Iyer AM, Spliet WG, Ferrier CH, van Rijen PC, Veersema TJ, Thom M, Schouten-van Meeteren AY, Reijneveld JC, Ylstra B, Wesseling P, Aronica E Landscape of chromosomal copy number aberrations in gangliogliomas and dysembryoplastic neuroepithelial tumours. Neuropathol Appl Neurobiol 2015 Mar 7 Dysembryoplastic neuroepithelial tumour Next Generation Sequencing Homo sapiens 25764012_1 Illumina HiSeq 2000 Department of (Neuro)Pathology, University of Amsterdam, Amsterdam, The Netherlands AIM: Gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumours (DNTs) represent the most common histological entities within the spectrum of glioneuronal tumours (GNTs). The wide variability of morphological features complicates histological classification, including discrimination from prognostically distinct diffuse low-grade astrocytomas (AIIs). This study was performed to increase our understanding of these tumours. METHODS: We studied chromosomal copy number aberrations (CNAs) by genome-wide sequencing in a large cohort of GNTs and linked these to comprehensive histological analysis and clinical characteristics. One hundred fourteen GNTs were studied: 50 GGs and 64 DNTs. Also, a data set of CNAs from 38 diffuse AIIs was included. RESULTS: The most frequent CNAs in both GGs and DNTs were gains at chromosomes 5 and 7, often concurrent, and gain at chromosome 6. None of the CNAs was linked to histological subtype, immunohistochemical features or to clinical characteristics. Comparison of AIIs and diffuse GNTs revealed that gain at whole chromosome 5 is only observed in GNTs. CNA patterns indicative of chromothripsis were detected in three GNTs. CONCLUSION: We conclude that GNTs with diverse morphologies share molecular features, and our findings support the need to improve classification and differential diagnosis of tumour entities within the spectrum of GNTs, as well as their distinction from other gliomas. EGAS00001000831;EGAS00001000643 Yes NA CTDB0091 Research 25764012 Prabowo AS, van Thuijl HF, Scheinin I, Sie D, van Essen HF, Iyer AM, Spliet WG, Ferrier CH, van Rijen PC, Veersema TJ, Thom M, Schouten-van Meeteren AY, Reijneveld JC, Ylstra B, Wesseling P, Aronica E Landscape of chromosomal copy number aberrations in gangliogliomas and dysembryoplastic neuroepithelial tumours. Neuropathol Appl Neurobiol 2015 Mar 7 Dysembryoplastic neuroepithelial tumour Next Generation Sequencing Homo sapiens 25764012_2 Illumina HiSeq 2000 Department of (Neuro)Pathology, University of Amsterdam, Amsterdam, The Netherlands AIM: Gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumours (DNTs) represent the most common histological entities within the spectrum of glioneuronal tumours (GNTs). The wide variability of morphological features complicates histological classification, including discrimination from prognostically distinct diffuse low-grade astrocytomas (AIIs). This study was performed to increase our understanding of these tumours. METHODS: We studied chromosomal copy number aberrations (CNAs) by genome-wide sequencing in a large cohort of GNTs and linked these to comprehensive histological analysis and clinical characteristics. One hundred fourteen GNTs were studied: 50 GGs and 64 DNTs. Also, a data set of CNAs from 38 diffuse AIIs was included. RESULTS: The most frequent CNAs in both GGs and DNTs were gains at chromosomes 5 and 7, often concurrent, and gain at chromosome 6. None of the CNAs was linked to histological subtype, immunohistochemical features or to clinical characteristics. Comparison of AIIs and diffuse GNTs revealed that gain at whole chromosome 5 is only observed in GNTs. CNA patterns indicative of chromothripsis were detected in three GNTs. CONCLUSION: We conclude that GNTs with diverse morphologies share molecular features, and our findings support the need to improve classification and differential diagnosis of tumour entities within the spectrum of GNTs, as well as their distinction from other gliomas. EGAS00001000831;EGAS00001000643 Yes NA CTDB0092 Research 25764012 Prabowo AS, van Thuijl HF, Scheinin I, Sie D, van Essen HF, Iyer AM, Spliet WG, Ferrier CH, van Rijen PC, Veersema TJ, Thom M, Schouten-van Meeteren AY, Reijneveld JC, Ylstra B, Wesseling P, Aronica E Landscape of chromosomal copy number aberrations in gangliogliomas and dysembryoplastic neuroepithelial tumours. Neuropathol Appl Neurobiol 2015 Mar 7 Ganglioglioma Next Generation Sequencing Homo sapiens 25764012_3 Illumina HiSeq 2000 Department of (Neuro)Pathology, University of Amsterdam, Amsterdam, The Netherlands AIM: Gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumours (DNTs) represent the most common histological entities within the spectrum of glioneuronal tumours (GNTs). The wide variability of morphological features complicates histological classification, including discrimination from prognostically distinct diffuse low-grade astrocytomas (AIIs). This study was performed to increase our understanding of these tumours. METHODS: We studied chromosomal copy number aberrations (CNAs) by genome-wide sequencing in a large cohort of GNTs and linked these to comprehensive histological analysis and clinical characteristics. One hundred fourteen GNTs were studied: 50 GGs and 64 DNTs. Also, a data set of CNAs from 38 diffuse AIIs was included. RESULTS: The most frequent CNAs in both GGs and DNTs were gains at chromosomes 5 and 7, often concurrent, and gain at chromosome 6. None of the CNAs was linked to histological subtype, immunohistochemical features or to clinical characteristics. Comparison of AIIs and diffuse GNTs revealed that gain at whole chromosome 5 is only observed in GNTs. CNA patterns indicative of chromothripsis were detected in three GNTs. CONCLUSION: We conclude that GNTs with diverse morphologies share molecular features, and our findings support the need to improve classification and differential diagnosis of tumour entities within the spectrum of GNTs, as well as their distinction from other gliomas. EGAS00001000831;EGAS00001000643 Yes NA CTDB0095 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 1,4,12,13,15 Chronic lymphocytic leukemia Next Generation Sequencing Homo sapiens PD3172a Illumina Genome Analyzer II hs1:170758115-170758115,hs4:173998000-173998000;hs1:170822660-170822660,hs4:119852135-119852135;hs1:172107770-172107770,hs4:81649760-81649760;hs4:70257618-70257618,hs4:105957165-105957165;hs4:70261129-70261129,hs4:80291486-80291486;hs4:71223258-71223258,hs4:81652006-81652006;hs4:77014716-77014716,hs4:170643878-170643878;hs4:77030145-77030145,hs4:119951745-119951745;hs4:77030147-77030147,hs4:119849842-119849842;hs4:77037605-77037605,hs4:80293316-80293316;hs4:77040817-77040817,hs4:81648619-81648619;hs4:77040842-77040842,hs4:86837950-86837950;hs4:77042952-77042952,hs4:105696487-105696487;hs4:78650104-78650104,hs4:169386977-169386977;hs4:78651579-78651579,hs4:81649652-81649652;hs4:80226572-80226572,hs4:170624360-170624360;hs4:80226595-80226595,hs4:81313713-81313713;hs4:80287286-80287286,hs4:170642768-170642768;hs4:80291307-80291307,hs4:107243297-107243297;hs4:80467681-80467681,hs4:119852103-119852103;hs4:80506413-80506413,hs4:104234697-104234697;hs4:81648711-81648711,hs4:99640521-99640521;hs4:99639025-99639025,hs4:107217807-107217807;hs4:104243155-104243155,hs4:167629140-167629140;hs4:105652371-105652371,hs4:105957018-105957018;hs4:105652481-105652481,hs4:105967833-105967833;hs4:105662342-105662342,hs4:106201407-106201407;hs4:105700611-105700611,hs12:59712049-59712049;hs4:105739492-105739492,hs4:119952131-119952131;hs4:106197097-106197097,hs4:107243349-107243349;hs4:107216936-107216936,hs4:170645224-170645224;hs4:119501206-119501206,hs4:169381508-169381508;hs4:119956158-119956158,hs4:167620640-167620640;hs4:162402650-162402650,hs12:59468319-59468319;hs4:167620542-167620542,hs15:21792673-21792673;hs4:169386926-169386926,hs4:170642728-170642728;hs4:170624368-170624368,hs4:173997876-173997876;hs4:173959368-173959368,hs12:59539267-59539267;hs12:59707038-59707038,hs15:23138396-23138396;hs13:49474759-49474759,hs13:50488499-50488499;hs15:21280398-21280398,hs15:40811223-40811223;hs4:104234642-104234942,hs4:107217311-107217611;hs4:106199979-106200279,hs4:107220534-107220834;hs4:106201375-106201675,hs15:21786025-21786325;hs4:80506144-80506444,hs15:21280101-21280401 TBCK_HUMAN;NEK1;ZBTB37;C4orf22 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes ZBTB37,C4orf22;TBCK_HUMAN,NEK1 CTDB0096 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 4,9,13 Chronic lymphocytic leukemia Next Generation Sequencing Homo sapiens PD3175a Illumina Genome Analyzer II hs4:99985365-99985365,hs10:102805821-102805821;hs4:169615303-169615303,hs9:21789308-21789308;hs4:169770605-169770605,hs9:21457739-21457739;hs4:99990414-99990714,hs9:21464986-21465286;hs9:20322528-20322528,hs13:47760651-47760651;hs9:21465000-21465000,hs13:47765821-47765821;hs9:22237156-22237156,hs13:50426343-50426343;hs11:79215247-79215247,hs11:126343811-126343811;hs13:47298401-47298401,hs13:50430220-50430220 CDKN2A;miR-15a/16-1 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes NA CTDB0097 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 5 Renal cancer Next Generation Sequencing Homo sapiens TK10 Illumina Genome Analyzer II hs5:1391571-1391571,hs5:58882426-58882426;hs5:5997677-5997677,hs5:172885499-172885499;hs5:82591088-82591088,hs5:87333255-87333255;hs5:150892726-150892726,hs5:179506251-179506251;hs5:116036409-116036709,hs5:121979782-121980082;hs5:40837990-40837990,hs5:155087856-155087856;hs5:122724312-122724312,hs5:149292657-149292657;hs5:80245290-80245290,hs5:88043252-88043252;hs5:30903628-30903628,hs5:179575729-179575729;hs5:176692704-176693004,hs5:176849251-176849551;hs5:14835731-14836031,hs5:154507851-154508151;hs5:155231047-155231047,hs5:155239167-155239167;hs5:10681875-10681875,hs5:115348662-115348662;hs5:93783789-93783789,hs5:118735125-118735125;hs5:8009373-8009673,hs5:158710597-158710897;hs5:58427832-58427832,hs5:81386796-81386796;hs5:16203070-16203070,hs5:171178291-171178291;hs5:156463031-156463031,hs5:167283727-167283727;hs5:167251737-167251737,hs5:167283889-167283889;hs5:116036273-116036273,hs5:125175837-125175837;hs5:143377847-143377847,hs5:170778628-170778628;hs5:149360242-149360242,hs5:159241778-159241778;hs5:40069776-40069776,hs5:167246377-167246377;hs5:65989166-65989466,hs5:150893224-150893524;hs5:1391961-1391961,hs5:40252955-40252955;hs5:170777227-170777527,hs5:171176733-171177033;hs5:17269304-17269304,hs5:130533138-130533138;hs5:25833862-25833862,hs5:41970498-41970498;hs5:164531274-164531274,hs5:170030775-170030775;hs5:85333134-85333134,hs5:93781890-93781890;hs5:20868092-20868092,hs5:34407621-34407621;hs5:82594065-82594065,hs5:93387598-93387598;hs5:115347784-115347784,hs5:116728213-116728213;hs5:10639936-10639936,hs5:81385621-81385621;hs5:116145701-116145701,hs5:124097158-124097158;hs5:116728965-116729265,hs5:164535526-164535826;hs5:114877024-114877024,hs5:114913231-114913231;hs5:118734017-118734017,hs5:143377782-143377782;hs5:142741896-142741896,hs5:172986135-172986135;hs5:102946493-102946493,hs5:110916800-110916800;hs5:4254208-4254208,hs5:85333005-85333005;hs5:146248274-146248274,hs5:149293070-149293070;hs5:73700457-73700457,hs5:95495199-95495199;hs5:110989909-110989909,hs5:171901209-171901209;hs5:110918352-110918352,hs5:154476395-154476395;hs5:87574938-87574938,hs5:119641592-119641592;hs5:4253813-4253813,hs5:8009710-8009710;hs5:13558101-13558101,hs5:24794276-24794276;hs5:10705318-10705318,hs5:149360688-149360688;hs5:84038311-84038311,hs5:96658107-96658107;hs5:32281581-32281581,hs5:66102085-66102085;hs5:93386712-93386712,hs5:124097383-124097383;hs5:14231532-14231532,hs5:129092795-129092795;hs5:41971777-41971777,hs5:157749099-157749099;hs5:148091942-148091942,hs5:154506363-154506363 LMAN2;C5orf21;CCDC100;PDLIM7;ZNF608;PDE6A Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes C5orf21,ZNF608;CCDC100,PDE6A;LMAN2,PDLIM7 CTDB0098 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 3,4,7,8,9 Chordoma Next Generation Sequencing Homo sapiens PD3808a Illumina Genome Analyzer II hs16:69265309-69265309,hs21:36237341-36237341;hs4:123124159-123124159,hs4:155159776-155159776;hs4:160244766-160244766,hs9:12975640-12975640;hs3:139340487-139340487,hs3:188568303-188568303;hs3:105009813-105009813,hs3:115981971-115981971;hs3:125751870-125751870,hs3:125997366-125997366;hs9:12406646-12406646,hs9:13055939-13055939;hs3:128893222-128893222,hs3:193227946-193227946;hs7:114409936-114409936,hs9:7316206-7316206;hs7:153836592-153836592,hs8:15649993-15649993;hs7:153199562-153199562,hs8:35945668-35945668;hs3:111440555-111440555,hs9:12598203-12598203;hs3:198269534-198269534,hs8:20151294-20151294;hs7:142008035-142008035,hs7:142194692-142194692;hs7:153541205-153541205,hs8:37921420-37921420;hs8:36069934-36069934,hs8:37943155-37943155;hs3:107391861-107391861,hs3:154927561-154927561;hs3:107458456-107458456,hs4:155589198-155589198;hs8:23182631-23182631,hs9:18177075-18177075;hs7:118260884-118260884,hs8:23089086-23089086;hs3:103437636-103437636,hs3:111344479-111344479;hs7:114353063-114353063,hs8:6297119-6297119;hs3:112126377-112126377,hs3:176209249-176209249;hs7:124797117-124797117,hs8:24255233-24255233;hs9:14680733-14680733,hs9:15703851-15703851;hs4:143617033-143617033,hs4:154386445-154386445;hs3:175287849-175287849,hs7:125094174-125094174;hs21:31753291-31753291,hs21:32980788-32980788;hs8:3380667-3380667,hs9:2183009-2183009;hs3:169305809-169305809,hs4:159579170-159579170;hs3:143632931-143632931,hs7:115987536-115987536;hs3:131029503-131029503,hs8:27510652-27510652;hs7:108221716-108221716,hs7:111876430-111876430;hs8:2259557-2259557,hs9:5099157-5099157;hs4:155125184-155125184,hs4:155164041-155164041;hs3:185109118-185109118,hs8:22917884-22917884;hs3:109188323-109188323,hs8:13206097-13206097;hs3:104112605-104112605,hs8:31816236-31816236;hs3:173006812-173006812,hs3:179412453-179412453;hs4:154567973-154568273,hs8:20975643-20975943;hs3:139342416-139342716,hs8:22732250-22732550;hs7:108220627-108220927,hs8:40732209-40732509;hs3:169230059-169230359,hs7:114812766-114813066;hs3:188647808-188648108,hs4:147925705-147926005;hs7:111428079-111428379,hs7:114488081-114488381;hs4:155825482-155825782,hs8:31903051-31903351;hs3:125730301-125730301,hs3:125985653-125985653;hs3:104685671-104685971,hs4:157499321-157499621;hs7:124355725-124356025,hs9:13630760-13631060;hs3:125262369-125262369,hs3:157388224-157388224;hs3:129206188-129206488,hs3:148104334-148104634;hs3:185809534-185809834,hs9:3851333-3851633;hs3:127741362-127741662,hs7:150238171-150238471;hs7:117939595-117939895,hs9:18090627-18090927;hs4:156554532-156554532,hs8:40025625-40025625;hs4:147352460-147352460,hs7:153709547-153709547;hs3:127952177-127952177,hs9:9227307-9227307;hs3:46413547-46413547,hs19:46781534-46781534;hs3:194586374-194586374,hs8:3671798-3671798;hs3:162491470-162491470,hs7:121614819-121614819;hs3:166314683-166314683,hs7:107455505-107455505;hs3:130680026-130680026,hs3:150022346-150022346;hs3:150022492-150022492,hs9:14521843-14521843;hs3:46414148-46414148,hs22:18459484-18459484;hs3:164420972-164420972,hs3:164591947-164591947;hs7:105982090-105982090,hs7:124219623-124219623;hs21:33477317-33477317,hs21:35741213-35741213;hs8:15518658-15518658,hs9:24805672-24805672;hs7:123687423-123687423,hs9:7745598-7745598;hs4:157378862-157378862,hs8:29283626-29283626;hs3:138664031-138664031,hs8:24040020-24040020;hs3:158987767-158987767,hs3:191886018-191886018;hs3:108235308-108235308,hs8:35956663-35956663;hs3:168438541-168438541,hs7:118533955-118533955;hs4:155594968-155594968,hs8:28111767-28111767;hs7:108225342-108225342,hs7:112844222-112844222;hs3:144533104-144533104,hs8:37921782-37921782;hs3:164360375-164360375,hs3:190445467-190445467;hs7:122617539-122617539,hs7:123024103-123024103;hs7:103750502-103750502,hs8:38708000-38708000;hs3:97874051-97874051,hs7:112292247-112292247;hs20:52206438-52206438,hs20:52208530-52208530;hs3:141643303-141643303,hs3:180957055-180957055;hs3:129207203-129207203,hs3:156247362-156247362;hs3:11862467-11862467,hs20:2071667-2071667;hs3:149087043-149087043,hs8:39311333-39311333;hs8:19904290-19904590,hs9:20235876-20236176;hs4:155970697-155970697,hs4:156555443-156555443;hs3:118147498-118147498,hs8:36363040-36363040;hs4:156544080-156544080,hs9:12947309-12947309;hs3:102910471-102910471,hs7:124918640-124918640;hs3:144477589-144477589,hs9:1779626-1779626;hs8:20056378-20056378,hs8:39016067-39016067;hs3:149088054-149088354,hs7:117440947-117441247;hs8:15503001-15503301,hs8:39740184-39740484;hs3:103438814-103439114,hs9:19858660-19858960;hs3:116916724-116917024,hs9:25264982-25265282;hs3:156286767-156287067,hs7:116119258-116119558;hs3:127951124-127951424,hs7:150837060-150837360;hs8:15525786-15526086,hs9:21422589-21422889;hs3:120930878-120931178,hs8:6347796-6348096;hs7:122408422-122408722,hs9:7744692-7744992;hs4:147347813-147348113,hs9:11837349-11837649;hs3:152844675-152844975,hs7:122408596-122408896;hs3:146637952-146638252,hs9:2207720-2208020;hs3:104155150-104155450,hs7:115370000-115370300;hs3:128284411-128284411,hs3:180373930-180373930;hs7:119836543-119836543,hs9:25500198-25500198;hs7:123687797-123687797,hs7:153838854-153838854;hs3:128109352-128109352,hs9:25268743-25268743;hs3:154774713-154774713,hs3:173287445-173287445;hs9:15701275-15701275,hs9:25499115-25499115;hs3:107662905-107662905,hs9:2190011-2190011;hs3:46444610-46444610,hs20:2071650-2071650;hs3:125352173-125352173,hs8:22646611-22646611;hs3:158524792-158524792,hs3:184617021-184617021;hs4:139321025-139321025,hs4:146191241-146191241;hs3:151771683-151771683,hs3:152589872-152589872;hs3:168285644-168285644,hs9:4260865-4260865;hs7:121353313-121353613,hs9:7099534-7099834;hs4:157707846-157707846,hs8:38761159-38761159;hs8:38761237-38761237,hs8:38761149-38761149;hs9:7747212-7747212,hs4:155273908-155273908;hs4:155274085-155274085,hs9:9226929-9226929;hs21:32630281-32630281,hs21:32912080-32912080;hs3:112147066-112147066,hs9:8103232-8103232;hs8:31138391-31138391,hs9:25261892-25261892;hs8:2231764-2231764,hs9:18482965-18482965;hs3:180862807-180862807,hs8:32257425-32257425;hs3:112126103-112126103,hs9:2429938-2429938;hs7:153024497-153024497,hs7:154641891-154641891;hs7:104820921-104820921,hs8:27318072-27318072;hs4:146050567-146050567,hs7:115301055-115301055;hs3:120930617-120930617,hs3:144865567-144865567;hs3:144865662-144865662,hs7:152461589-152461589;hs4:156105496-156105496,hs8:36360314-36360314;hs9:7745569-7745569,hs9:13772276-13772276;hs8:20044621-20044621,hs8:20142853-20142853;hs4:146392191-146392191,hs7:150250515-150250515;hs3:177449668-177449668,hs3:192448991-192448991;hs3:117334062-117334062,hs3:143242427-143242427;hs7:119976170-119976470,hs9:20437254-20437554;hs4:153860047-153860047,hs7:118141668-118141668;hs3:143382263-143382263,hs7:107457427-107457427;hs3:129900482-129900482,hs4:149546422-149546422;hs7:126683395-126683395,hs13:103858404-103858404;hs3:183749920-183749920,hs8:22655471-22655471;hs7:105491465-105491765,hs8:31824417-31824717;hs3:155933574-155933574,hs3:156698309-156698309;hs7:106884075-106884075,hs8:6956600-6956600;hs7:124225398-124225398,hs8:2241777-2241777;hs4:156542260-156542260,hs4:161419859-161419859;hs3:108317484-108317484,hs8:16279341-16279341;hs7:150801149-150801149,hs7:150897299-150897299;hs3:194813394-194813394,hs8:36122902-36122902;hs3:107518475-107518475,hs9:9672987-9672987;hs7:121866153-121866153,hs8:14156577-14156577;hs9:21784393-21784693,hs9:22291400-22291700 CDKN2A;CLU;DPP6;KCND2;MCPH1;MDFIC;MET;MLLT3;MME;PRKAG2;RHEB;TMCC1;TUSC3;WRN Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes DPP6,TUSC3;KCND2,MLLT3;MDFIC,MCPH1;MME,MET;RHEB,PRKAG2;TMCC1,CLU CTDB0099 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 1,3,8,14 Chordoma Next Generation Sequencing Homo sapiens PD3807a Illumina Genome Analyzer II hs1:26979575-26979875,hs8:69957063-69957363;hs1:30245671-30245671,hs1:38399550-38399550;hs1:31899334-31899334,hs3:150466521-150466521;hs1:31940315-31940315,hs8:919665-919665;hs1:32720036-32720036,hs8:69724087-69724087;hs1:34451346-34451346,hs3:152144281-152144281;hs1:39264122-39264122,hs8:69723165-69723165;hs1:50992002-50992002,hs8:55720159-55720159;hs1:70901720-70902020,hs8:50147581-50147881;hs1:71137728-71137728,hs5:139904720-139904720;hs3:2601916-2601916,hs14:76184263-76184263;hs3:2610083-2610083,hs5:140127749-140127749;hs3:3416718-3416718,hs14:67892033-67892033;hs3:11255004-11255004,hs3:20403223-20403223;hs3:16643353-16643353,hs14:104931398-104931398;hs3:20085341-20085341,hs3:157751761-157751761;hs3:32621814-32621814,hs3:151850188-151850188;hs3:53410516-53410516,hs3:146734291-146734291;hs3:57325976-57325976,hs14:76400221-76400221;hs3:58931785-58931785,hs8:69681901-69681901;hs3:58938129-58938129,hs3:60835256-60835256;hs3:64565291-64565291,hs8:57311429-57311429;hs3:129929497-129929797,hs14:94268591-94268891;hs3:130245385-130245385,hs14:68408332-68408332;hs3:136003981-136003981,hs8:87003917-87003917;hs3:136449926-136449926,hs3:158026243-158026243;hs3:141305365-141305365,hs3:141412115-141412115;hs3:146735572-146735572,hs8:56175908-56175908;hs3:146736430-146736430,hs14:75887005-75887005;hs3:161812795-161812795,hs5:139768903-139768903;hs5:109933566-109933566,hs5:119200299-119200299;hs8:50147822-50147822,hs14:94729283-94729283;hs8:50489945-50489945,hs8:87018123-87018123;hs8:55439756-55439756,hs14:102320080-102320080;hs8:55723885-55723885,hs8:87283463-87283463;hs8:67128213-67128213,hs14:94141759-94141759;hs8:69722663-69722963,hs14:75864127-75864427;hs8:69945067-69945067,hs14:67894685-67894685;hs14:68271232-68271232,hs14:93541559-93541559;hs16:68497215-68497215,hs16:73317076-73317076;hs3:140998678-140998978,hs8:56176216-56176516;hs1:70998381-70998681,hs14:104931320-104931620;hs1:32719745-32720045,hs3:161742587-161742887 ARID1A Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes NA CTDB0100 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 8 Small cell lung cancer Next Generation Sequencing Homo sapiens SCLC-21H Illumina Genome Analyzer II hs8:11334999-11334999,hs8:66529146-66529146;hs8:127488904-127489204,hs8:128760986-128761286;hs8:90066845-90066845,hs8:128859930-128859930;hs8:11330938-11331238,hs8:116315947-116316247;hs8:29625873-29625873,hs8:127545025-127545025;hs8:40494959-40495259,hs8:63578821-63579121;hs8:84078541-84078541,hs8:128774769-128774769;hs1:1104523-1104523,hs8:11303277-11303277;hs8:66433321-66433321,hs8:99226664-99226664;hs8:41381707-41381707,hs8:55578459-55578459;hs8:63584884-63584884,hs8:128840413-128840413;hs8:84096378-84096678,hs8:99276752-99277052;hs8:40540106-40540106,hs8:41382086-41382086;hs8:40339604-40339604,hs8:63659251-63659251;hs1:13658511-13658511,hs8:99232476-99232476;hs8:84104510-84104510,hs8:99330308-99330308;hs8:89927992-89927992,hs8:116377775-116377775;hs8:90028640-90028640,hs8:128761665-128761665;hs8:63602392-63602692,hs8:84121444-84121744;hs8:55612264-55612264,hs8:63246121-63246121;hs8:66498393-66498393,hs8:99256919-99256919;hs8:66447224-66447224,hs8:127528434-127528434;hs8:40355992-40355992,hs8:66481086-66481086;hs8:11269759-11269759,hs8:89936178-89936178;hs8:89956203-89956203,hs8:128765822-128765822;hs8:10621584-10621884,hs8:49802227-49802527;hs8:99273289-99273289,hs8:99280579-99280579;hs8:89954833-89954833,hs8:116356805-116356805;hs8:76384607-76384907,hs8:134647332-134647632;hs8:1003824-1003824,hs8:141999833-141999833;hs8:99318074-99318074,hs8:116325324-116325324;hs8:29641114-29641414,hs8:90005403-90005703;hs8:91926266-91926266,hs8:135534499-135534499;hs8:11252027-11252027,hs8:112539264-112539264;hs8:11239955-11239955,hs8:136340239-136340239;hs8:121837279-121837279,hs8:123774622-123774622;hs8:6667546-6667546,hs8:140843361-140843361;hs8:53604722-53605022,hs8:119331475-119331775;hs8:12622845-12623145,hs8:37781847-37782147;hs8:69085526-69085526,hs8:72157502-72157502;hs8:5921124-5921124,hs8:37922786-37922786;hs8:63424515-63424515,hs8:128768887-128768887;hs8:66451200-66451200,hs8:89934797-89934797;hs8:73092898-73092898,hs8:75122245-75122245;hs8:5923169-5923169,hs8:37103136-37103136;hs8:42555739-42556039,hs8:53416356-53416656;hs8:40344813-40344813,hs8:63613246-63613246;hs8:135261511-135261511,hs8:135459132-135459132;hs8:11318167-11318167,hs8:11325275-11325275;hs8:137408686-137408986,hs8:138979784-138980084;hs8:81970352-81970352,hs8:133921212-133921212;hs8:5577388-5577388,hs8:103976608-103976608;hs8:10869550-10869850,hs8:137489525-137489825;hs8:22454965-22454965,hs8:133758654-133758654;hs8:30198404-30198404,hs8:87186559-87186559;hs8:81490029-81490329,hs8:82207940-82208240;hs8:101805541-101805541,hs8:137328228-137328228;hs8:87195716-87196016,hs8:124310623-124310923;hs8:20165449-20165449,hs8:137411964-137411964;hs8:20715579-20715579,hs8:63840620-63840620;hs8:19455939-19456239,hs8:139725272-139725572;hs8:1885157-1885157,hs8:110183787-110183787;hs8:6439903-6439903,hs8:30899422-30899422;hs8:41698217-41698517,hs8:49711469-49711769;hs8:41531133-41531133,hs8:119159124-119159124;hs1:13722829-13722829,hs8:3402262-3402262;hs8:16740459-16740759,hs8:42436126-42436426;hs8:48923911-48923911,hs8:122969508-122969508;hs8:57061907-57061907,hs8:129237641-129237641;hs8:58330935-58330935,hs8:82283446-82283446;hs8:6436982-6436982,hs8:41378046-41378046;hs8:41378099-41378099,hs8:108886771-108886771;hs8:53082840-53082840,hs8:78461441-78461441;hs8:116275853-116275853,hs8:128828742-128828742;hs8:15704777-15704777,hs8:134608299-134608299;hs8:63090960-63090960,hs8:135329445-135329445;hs8:13586559-13586559,hs8:41787159-41787159;hs8:54855118-54855118,hs8:99974406-99974406;hs8:123883526-123883826,hs8:140842856-140843156;hs8:82709329-82709329,hs8:97955601-97955601;hs8:72083508-72083508,hs8:85848430-85848430;hs8:34648964-34648964,hs8:48847974-48847974;hs8:36361896-36361896,hs8:138502485-138502485;hs8:66479937-66480237,hs8:128825952-128826252;hs8:5176476-5176776,hs8:10727886-10728186;hs8:35832972-35832972,hs8:91411528-91411528;hs8:4370669-4370669,hs8:13784748-13784748;hs8:93723994-93723994,hs8:128402490-128402490;hs8:56516542-56516842,hs8:136073825-136074125;hs8:41455693-41455693,hs8:100196980-100196980;hs8:10648768-10649068,hs8:10712705-10713005;hs8:92636326-92636326,hs8:138924823-138924823;hs8:114147202-114147202,hs8:137491376-137491376;hs8:78324898-78324898,hs8:109073814-109073814;hs8:73877924-73877924,hs8:91348505-91348505;hs8:91348628-91348628,hs8:74002719-74002719;hs8:68133797-68133797,hs8:109759771-109759771;hs8:53708080-53708080,hs8:56789717-56789717;hs8:33447354-33447654,hs8:102357702-102358002;hs8:33646395-33646395,hs8:123077634-123077634;hs8:66629238-66629238,hs8:97684801-97684801;hs8:66438322-66438322,hs8:66509837-66509837;hs8:116188868-116188868,hs8:116193675-116193675;hs8:20312061-20312061,hs8:23887740-23887740;hs8:42495902-42495902,hs8:52109083-52109083;hs8:11329042-11329342,hs8:90066559-90066859;hs8:3354213-3354213,hs8:114008570-114008570;hs8:104149665-104149665,hs8:131922039-131922039;hs8:65277352-65277352,hs8:66084082-66084082;hs8:66084167-66084167,hs8:95888502-95888502;hs8:16829036-16829336,hs8:135763578-135763878;hs8:2015035-2015035,hs8:23496027-23496027;hs8:20159816-20160116,hs8:89636443-89636743;hs8:22473575-22473875,hs8:28465450-28465750;hs8:96657888-96657888,hs8:104919780-104919780;hs1:13703176-13703176,hs8:129208802-129208802;hs8:129208955-129208955,hs8:53726328-53726328;hs8:9943872-9943872,hs8:13737829-13737829;hs8:121865821-121865821,hs8:132063003-132063003;hs8:70536958-70537258,hs8:135678550-135678850;hs8:115115068-115115068,hs8:124498649-124498649;hs8:87804017-87804017,hs8:89399047-89399047;hs8:29595171-29595171,hs8:101779643-101779643;hs8:63661067-63661067,hs8:65254844-65254844;hs8:33964222-33964222,hs8:84796563-84796563;hs8:20261536-20261536,hs8:104456656-104456656;hs8:19340160-19340160,hs8:108906676-108906676;hs8:90020658-90020658,hs8:90020621-90020621;hs8:90020642-90020642,hs8:99246395-99246395;hs8:78918625-78918925,hs8:121838655-121838955;hs8:90008816-90008816,hs8:90033567-90033567;hs8:23823139-23823139,hs8:38244838-38244838;hs8:66488653-66488653,hs8:66488637-66488637;hs8:66488655-66488655,hs8:116359919-116359919;hs8:38687783-38688083,hs8:55115556-55115856;hs8:10065124-10065124,hs8:140648461-140648461;hs8:104098523-104098523,hs8:21941749-21941749;hs8:21941882-21941882,hs8:123881299-123881299;hs8:23884048-23884048,hs8:36446115-36446115;hs8:23314804-23314804,hs8:111209464-111209464;hs8:32775300-32775300,hs8:54833719-54833719;hs8:30719989-30720289,hs8:112130423-112130723;hs8:73713237-73713237,hs8:95036144-95036144;hs8:5702350-5702350,hs8:62118452-62118452;hs8:19556614-19556614,hs8:123989457-123989457;hs8:41252177-41252177,hs8:115209623-115209623;hs8:12831396-12831396,hs8:40132030-40132030;hs8:17259473-17259773,hs8:53074678-53074978;hs8:94072576-94072576,hs8:95042628-95042628;hs8:34089229-34089229,hs8:97686951-97686951;hs8:64744240-64744540,hs8:109694614-109694914;hs8:106848265-106848565,hs8:123778997-123779297;hs8:11876864-11876864,hs8:18998093-18998093;hs8:81247021-81247021,hs8:106849803-106849803;hs8:106849700-106849700,hs8:122236671-122236671;hs8:11294662-11294662,hs8:90025359-90025359;hs8:90056153-90056153,hs8:128792934-128792934;hs8:25893544-25893544,hs8:79764491-79764491;hs8:66498808-66499108,hs8:116356139-116356439;hs8:23331179-23331479,hs8:54715473-54715773;hs8:79753603-79753603,hs8:104331455-104331455;hs8:39025676-39025676,hs8:84505221-84505221;hs8:16739444-16739444,hs8:135274289-135274289;hs8:100269659-100269659,hs8:108247116-108247116;hs8:61005553-61005553,hs8:125528765-125528765;hs8:75470433-75470433,hs8:123074743-123074743;hs8:65992307-65992307,hs8:138798601-138798601;hs8:42637553-42637553,hs8:133603327-133603327;hs8:66631135-66631135,hs8:93735785-93735785;hs8:19003344-19003344,hs8:19450295-19450295 GINS4;EXT1 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes GINS4,EXT1 CTDB0101 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 15 Colorectal cancer Next Generation Sequencing Homo sapiens SNU-C1 Illumina Genome Analyzer II hs5:109293270-109293270,hs5:115682772-115682772;hs15:42645429-42645429,hs15:61036133-61036133;hs15:73295567-73295567,hs15:89764559-89764559;hs15:64854283-64854283,hs15:72235517-72235517;hs15:61253592-61253592,hs15:91339377-91339377;hs15:54752383-54752383,hs15:98905233-98905233;hs15:25910101-25910101,hs15:38751185-38751185;hs15:89776273-89776273,hs15:90293606-90293606;hs8:40721876-40721876,hs8:41886487-41886487;hs15:70535278-70535278,hs15:70836792-70836792;hs15:58059812-58059812,hs15:60388368-60388368;hs15:69892160-69892160,hs15:73297296-73297296;hs15:37589405-37589405,hs15:65750113-65750113;hs15:65750170-65750170,hs15:65750280-65750280;hs15:65750188-65750188,hs15:45790516-45790516;hs15:56340355-56340355,hs15:88007541-88007541;hs8:40178261-40178261,hs8:40719925-40719925;hs15:79275381-79275381,hs15:90345243-90345243;hs15:38774912-38774912,hs15:61154715-61154715;hs15:58102331-58102331,hs15:71416015-71416015;hs15:29011718-29011718,hs15:80084016-80084016;hs15:78453171-78453171,hs15:96892792-96892792;hs15:63534551-63534551,hs15:75481966-75481966;hs5:4053020-4053020,hs5:4057146-4057146;hs5:4057180-4057180,hs5:19410043-19410043;hs5:19409998-19409998,hs5:19334163-19334163;hs15:54976612-54976612,hs15:73281849-73281849;hs15:45179195-45179195,hs15:50412615-50412615;hs15:31236867-31236867,hs15:65794835-65794835;hs15:42643401-42643401,hs15:45121211-45121211;hs15:72205941-72205941,hs15:73819066-73819066;hs15:71329200-71329200,hs15:91478561-91478561;hs8:40175132-40175132,hs8:41885692-41885692;hs15:36641115-36641115,hs15:41564289-41564289;hs15:41564378-41564378,hs15:36682020-36682020;hs15:31664387-31664387,hs15:63585057-63585057;hs8:85742683-85742683,hs8:90088151-90088151;hs8:41850993-41850993,hs8:41892659-41892659;hs15:40196241-40196241,hs15:69845172-69845172;hs15:69892200-69892200,hs15:99842275-99842275;hs1:199103044-199103044,hs1:207179162-207179162;hs15:33102625-33102625,hs15:33103921-33103921;hs15:36187175-36187175,hs15:73296060-73296060;hs15:73296178-73296178,hs15:71521793-71521793;hs15:50541752-50541752,hs15:79276272-79276272;hs15:79276097-79276097,hs15:56374249-56374249;hs15:37484165-37484165,hs15:60659780-60659780;hs15:57927463-57927463,hs15:97396758-97396758;hs15:40193388-40193388,hs15:75393153-75393153;hs15:31983222-31983222,hs15:72083359-72083359;hs15:32994983-32994983,hs15:32995155-32995155;hs15:55045732-55045732,hs15:91324428-91324428;hs15:57888866-57888866,hs15:79317019-79317019;hs15:79317047-79317047,hs15:73298996-73298996;hs15:68071729-68071729,hs15:71830687-71830687;hs15:63320707-63320707,hs15:63467038-63467038;hs15:36726323-36726323,hs15:68419057-68419057;hs8:41788867-41788867,hs8:41850160-41850160;hs15:22525036-22525036,hs15:22533886-22533886;hs15:27907829-27907829,hs15:99233236-99233236;hs15:36175800-36175800,hs15:64787319-64787319;hs15:71920251-71920251,hs15:87138544-87138544;hs15:40761448-40761448,hs15:66051604-66051604;hs8:41849557-41849557,hs18:27370041-27370041;hs15:36638378-36638378,hs15:98918942-98918942;hs8:40343657-40343657,hs8:41893298-41893298;hs15:96904664-96904664,hs15:97363040-97363040;hs15:39821708-39821708,hs15:56357010-56357010;hs15:41614696-41614696,hs15:57199825-57199825;hs15:65432900-65432900,hs15:67396360-67396360;hs15:38741422-38741422,hs15:71749049-71749049;hs5:8111265-8111265,hs5:9418712-9418712;hs15:57931616-57931616,hs15:61043059-61043059;hs15:83156118-83156118,hs15:89341138-89341138;hs15:36263113-36263113,hs15:64125836-64125836;hs15:73298345-73298345,hs15:73302316-73302316;hs15:65791163-65791163,hs15:80125022-80125022;hs15:73247557-73247557,hs15:89860904-89860904;hs15:70964797-70964797,hs15:75030116-75030116;hs15:70936517-70936517,hs15:96935631-96935631;hs15:31629722-31629722,hs15:99973340-99973340;hs15:75398338-75398338,hs15:75399092-75399092;hs15:22538311-22538311,hs15:71955889-71955889;hs15:60795087-60795387,hs15:70574704-70575004;hs15:42630355-42630355,hs15:42632397-42632397;hs15:20666179-20666479,hs15:75434177-75434477;hs15:46507201-46507201,hs15:56341165-56341165;hs15:40239922-40239922,hs15:45838876-45838876;hs15:71523563-71523563,hs15:92082499-92082499;hs15:60861750-60861750,hs15:67014720-67014720;hs15:38770444-38770444,hs15:60861448-60861448;hs15:62166717-62166717,hs15:79091964-79091964;hs15:21792946-21792946,hs15:37804550-37804550;hs15:59129294-59129294,hs15:61587347-61587347;hs15:32034374-32034374,hs15:36263597-36263597;hs15:90984603-90984603,hs15:90985184-90985184;hs15:31254990-31254990,hs15:69830761-69830761;hs15:20439260-20439260,hs15:58108479-58108479;hs15:25911491-25911791,hs15:40795032-40795332;hs15:55145631-55145631,hs15:91059027-91059027;hs15:61684723-61684723,hs15:99949359-99949359;hs15:65288829-65288829,hs15:99230688-99230688;hs15:73207500-73207500,hs15:79085430-79085430;hs15:40215424-40215424,hs15:40216028-40216028;hs15:58102902-58102902,hs15:83673818-83673818;hs15:46555106-46555106,hs15:89867104-89867104;hs15:39931664-39931664,hs15:67912359-67912359;hs15:40785816-40785816,hs15:75522080-75522080;hs15:33461234-33461234,hs15:91924930-91924930;hs15:91924909-91924909,hs15:57155586-57155586;hs15:20233523-20233523,hs15:41614683-41614683;hs3:4701765-4701765,hs11:13182721-13182721;hs3:48906651-48906651,hs11:23642584-23642584;hs15:46453422-46453422,hs15:56041029-56041029;hs15:64494684-64494684,hs15:91502359-91502359;hs15:32005037-32005037,hs15:90971265-90971265;hs15:35747863-35747863,hs15:37540088-37540088;hs15:58159305-58159305,hs15:79078615-79078615;hs15:65285591-65285591,hs15:88004167-88004167;hs15:76247726-76247726,hs15:91051056-91051056;hs15:42858926-42858926,hs15:42859266-42859266;hs15:68070801-68070801,hs15:98695580-98695580;hs15:60866944-60867244,hs15:61033033-61033333;hs15:22525085-22525085,hs15:22525788-22525788;hs15:22525832-22525832,hs15:26819408-26819408;hs15:55039512-55039512,hs15:91310222-91310222;hs15:83663246-83663546,hs15:91038651-91038951;hs15:40191067-40191367,hs15:50349914-50350214;hs15:20442152-20442452,hs15:34062543-34062843;hs15:62491216-62491216,hs15:69900499-69900499;hs3:87548734-87548734,hs11:35317771-35317771;hs15:45763165-45763165,hs15:92052826-92052826;hs15:76213159-76213159,hs15:99934689-99934689;hs15:78961715-78961715,hs15:99202645-99202645;hs15:36267103-36267103,hs15:50465525-50465525;hs15:20450115-20450115,hs15:20535877-20535877;hs15:27999645-27999645,hs15:32004981-32004981;hs15:62473216-62473216,hs15:91494734-91494734;hs15:35713855-35713855,hs15:54817105-54817105;hs15:66051537-66051537,hs15:66064919-66064919;hs15:36819566-36819566,hs15:41536880-41536880;hs15:55155375-55155375,hs15:91494667-91494667;hs15:91494693-91494693,hs15:88487858-88487858;hs15:25911444-25911444,hs15:73209935-73209935;hs15:63613155-63613455,hs15:64492060-64492360;hs15:43273009-43273009,hs15:72291125-72291125;hs15:65444093-65444093,hs15:67353341-67353341;hs17:47583179-47583179,hs17:47673588-47673588;hs15:21304701-21304701,hs15:60702415-60702415;hs15:22520693-22520693,hs15:60561749-60561749;hs15:56351392-56351392,hs15:61034269-61034269;hs15:31929123-31929123,hs15:42858869-42858869;hs15:64265708-64265708,hs15:64504677-64504677;hs15:27938232-27938232,hs15:64814986-64814986;hs15:88446297-88446597,hs15:91858682-91858982;hs15:62473557-62473557,hs15:75968477-75968477;hs15:75968445-75968445,hs15:99982547-99982547;hs15:70528849-70528849,hs15:99973246-99973246;hs15:22668086-22668086,hs15:22669830-22669830;hs15:67910382-67910382,hs15:97388588-97388588;hs15:97388414-97388414,hs15:91927263-91927263;hs15:56340188-56340188,hs15:71445698-71445698;hs15:60561565-60561565,hs15:60561831-60561831;hs15:31461022-31461022,hs15:36625932-36625932;hs15:42859260-42859260,hs15:71506457-71506457;hs3:87543557-87543557,hs11:13184856-13184856;hs15:56356683-56356683,hs15:97506984-97506984;hs16:49042448-49042448,hs16:49264252-49264252;hs15:80089165-80089165,hs15:89714825-89714825;hs15:21437441-21437441,hs15:52967503-52967503;hs15:70535066-70535066,hs15:73247894-73247894;hs15:68526661-68526661,hs15:75435335-75435335;hs15:53442839-53442839,hs15:53444364-53444364;hs15:41620892-41620892,hs15:42885739-42885739;hs15:42885773-42885773,hs15:61637310-61637310;hs15:20449913-20449913,hs15:61647476-61647476;hs15:96906227-96906227,hs15:98804709-98804709;hs15:31239124-31239124,hs15:70778744-70778744;hs15:61033017-61033017,hs15:91491722-91491722;hs15:60642550-60642550,hs15:94000718-94000718;hs15:61239607-61239607,hs15:90984622-90984622;hs15:65429521-65429521,hs15:65437469-65437469;hs15:31922566-31922566,hs15:31947771-31947771;hs15:71213961-71213961,hs15:96955824-96955824;hs15:60866497-60866497,hs15:62498953-62498953;hs15:79316338-79316338,hs15:91924945-91924945;hs15:36653682-36653682,hs15:98700528-98700528;hs15:60914215-60914215,hs15:89340355-89340355;hs15:54770658-54770658,hs15:76198556-76198556;hs15:31601519-31601519,hs15:72139674-72139674;hs15:45814941-45814941,hs15:89722206-89722206;hs15:31586956-31586956,hs15:72101680-72101680;hs15:72101746-72101746,hs15:98624129-98624129;hs15:71474848-71474848,hs15:73844953-73844953;hs15:57191730-57191730,hs15:75470310-75470310;hs15:63566357-63566357,hs15:67943079-67943079;hs15:76248986-76248986,hs15:94011553-94011553;hs15:78454199-78454199,hs15:96910635-96910635;hs15:72583384-72583384,hs15:83676828-83676828;hs15:71784115-71784115,hs15:76230619-76230619;hs15:76230487-76230487,hs15:83680532-83680532;hs15:39073718-39073718,hs15:72496041-72496041;hs15:72495903-72495903,hs15:60561742-60561742;hs15:56141934-56141934,hs15:69744498-69744498;hs15:73798593-73798893,hs15:88378258-88378558;hs8:41755853-41755853,hs8:41843392-41843392;hs15:62115554-62115554,hs15:66955306-66955306;hs15:36825165-36825165,hs15:37539946-37539946;hs15:22760734-22760734,hs15:28997353-28997353;hs15:28996817-28996817,hs15:54976948-54976948;hs9:122857324-122857324,hs9:123000890-123000890;hs15:31688027-31688327,hs15:83150880-83151180;hs15:33460471-33460471,hs15:62473233-62473233;hs15:42674253-42674253,hs15:62106324-62106324;hs15:69760634-69760634,hs15:96910513-96910513;hs15:27954928-27955228,hs15:36604216-36604516;hs15:32983684-32983684,hs15:100153615-100153615;hs15:75615998-75615998,hs15:98804766-98804766;hs15:34059307-34059307,hs15:91846730-91846730;hs15:27946388-27946388,hs15:62386491-62386491;hs15:36751203-36751203,hs15:99202584-99202584;hs15:37588095-37588395,hs15:67907765-67908065;hs15:70561093-70561093,hs15:70929346-70929346;hs15:62116806-62116806,hs15:80187947-80187947;hs8:40720418-40720418,hs8:41844665-41844665;hs15:61148109-61148109,hs15:70902144-70902144;hs15:57170466-57170466,hs15:20359182-20359182;hs15:20359229-20359229,hs15:67868222-67868222;hs15:20611271-20611271,hs15:76246399-76246399;hs15:35882182-35882182,hs15:80065241-80065241;hs15:20643792-20643792,hs15:91834883-91834883;hs15:31950708-31950708,hs15:61087212-61087212;hs15:50541698-50541998,hs15:79276203-79276503;hs15:25726455-25726455,hs15:43506693-43506693;hs15:64511972-64512272,hs15:71724189-71724489;hs15:54825502-54825802,hs15:54979709-54980009;hs15:40795460-40795460,hs15:50530209-50530209;hs15:58158418-58158418,hs15:83199272-83199272;hs15:69879358-69879658,hs15:73913216-73913516;hs15:54990311-54990311,hs15:68340326-68340326;hs15:21319206-21319206,hs15:41823382-41823382;hs15:41823470-41823470,hs15:71487405-71487405;hs15:52771752-52771752,hs15:91039719-91039719;hs15:67348061-67348061,hs15:80185211-80185211;hs15:70902114-70902114,hs15:71183364-71183364;hs15:69834022-69834022,hs15:91050856-91050856;hs15:91050941-91050941,hs15:98750210-98750210;hs15:27915504-27915804,hs15:79080941-79081241;hs15:63340782-63340782,hs15:63467070-63467070;hs15:33460682-33460682,hs15:91925121-91925121;hs15:37588832-37588832,hs15:68494420-68494420;hs15:76239134-76239134,hs15:91846801-91846801;hs15:67912501-67912501,hs15:22126383-22126383;hs15:22126361-22126361,hs15:91925124-91925124;hsX:71571275-71571275,hsX:71618464-71618464;hs15:46555181-46555181,hs15:98677395-98677395;hs15:37589239-37589239,hs15:67908720-67908720;hs15:36240860-36241160,hs15:45179162-45179462;hs15:41614873-41614873,hs15:57931572-57931572;hs15:43276379-43276379,hs15:45757617-45757617;hs15:31198422-31198422,hs15:46480283-46480283;hs15:66065184-66065184,hs15:68493728-68493728;hs15:39760701-39760701,hs15:69657718-69657718 AVEN;CHD2;IDH2;MTMR15;PML;Q6UXQ8_HUMAN;RORA;RYR3;SNURF;TCF12;TRIM69;USP3 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes AVEN,PML;RORA,USP3;RYR3,PML;RYR3,TRIM69;SNURF,MTMR15;TCF12,CHD2;TCF12,Q6UXQ8_HUMAN CTDB0102 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 9 Thyroid cancer Next Generation Sequencing Homo sapiens 8505C Illumina Genome Analyzer II hs9:7454833-7454833,hs9:23145010-23145010;hs9:33098663-33098663,hs9:33789560-33789560;hs9:1579757-1580057,hs9:4663106-4663406;hs9:8949468-8949768,hs9:15540871-15541171;hs9:228188-228188,hs9:20424814-20424814;hs9:12762732-12762732,hs9:25879584-25879584;hs9:28587314-28587314,hs9:28670841-28670841;hs9:24506875-24506875,hs9:25193632-25193632;hs9:2952298-2952298,hs9:10667039-10667039;hs9:20852311-20852311,hs9:29560127-29560127;hs9:17454719-17454719,hs9:26368791-26368791;hs9:29419040-29419340,hs9:29660189-29660489;hs9:21777176-21777176,hs9:29568922-29568922;hs9:13145539-13145539,hs9:14221818-14221818;hs9:7980862-7980862,hs9:9928692-9928692;hs9:21948858-21948858,hs9:33397652-33397652;hs9:20453319-20453319,hs9:27238725-27238725;hs9:5100371-5100371,hs9:29054311-29054311;hs9:5889794-5889794,hs9:26668518-26668518;hs9:4422090-4422090,hs9:5116722-5116722;hs9:2290544-2290544,hs9:4605611-4605611;hs9:7247919-7247919,hs9:9929564-9929564;hs9:13512666-13512666,hs9:27132324-27132324;hs9:25058453-25058753,hs9:26498004-26498304;hs9:6019406-6019706,hs9:28380386-28380686;hs9:10765455-10765455,hs9:13039192-13039192;hs9:5011921-5011921,hs9:7764091-7764091;hs9:15143749-15143749,hs9:28595214-28595214;hs9:4651767-4651767,hs9:20901921-20901921;hs9:12737450-12737450,hs9:13124848-13124848;hs9:9373024-9373024,hs9:10071146-10071146;hs9:2506342-2506342,hs9:2644653-2644653;hs9:17724585-17724585,hs9:24527845-24527845;hs9:16442087-16442087,hs9:26864075-26864075;hs9:6089120-6089120,hs9:14603695-14603695;hs9:19499041-19499041,hs9:20013757-20013757;hs9:5055620-5055620,hs9:6317157-6317157;hs9:2859316-2859316,hs9:8867751-8867751;hs9:4591795-4591795,hs9:27240863-27240863;hs9:2138307-2138307,hs9:2719580-2719580;hs9:2852906-2852906,hs9:19629264-19629264;hs9:14293226-14293226,hs9:14513741-14513741;hs9:14322415-14322415,hs9:23245395-23245395;hs9:7955237-7955237,hs9:24407743-24407743;hs9:10323697-10323697,hs9:14426915-14426915;hs9:3262095-3262095,hs9:27825635-27825635;hs9:9415390-9415390,hs9:10722575-10722575;hs9:6366290-6366290,hs9:10018277-10018277;hs9:29619486-29619486,hs9:29691381-29691381;hs9:402038-402038,hs9:7374557-7374557;hs9:11704731-11704731,hs9:14050724-14050724;hs9:10359747-10359747,hs9:12587433-12587433;hs9:16395062-16395062,hs9:25840571-25840571;hs9:17644515-17644515,hs9:19650991-19650991;hs9:21724873-21724873,hs9:27350365-27350365;hs9:10626472-10626472,hs9:21786655-21786655;hs9:22382260-22382260,hs9:27758579-27758579;hs9:5288498-5288498,hs9:21459325-21459325;hs9:12418901-12418901,hs9:13734730-13734730;hs9:19502794-19503094,hs9:20827418-20827718;hs9:3104534-3104534,hs9:24190526-24190526;hs9:8934538-8934538,hs9:15718673-15718673;hs9:4507322-4507322,hs9:6998862-6998862;hs9:8588558-8588558,hs9:10067086-10067086;hs9:4716993-4716993,hs9:27515861-27515861;hs9:21912699-21912699,hs9:23468883-23468883;hs9:5080122-5080122,hs9:28373207-28373207;hs9:28470952-28470952,hs9:29452159-29452159;hs9:10747464-10747464,hs9:15140890-15140890;hs9:2773503-2773503,hs9:2826002-2826002;hs9:5020641-5020641,hs9:22930579-22930579;hs9:21029705-21029705,hs9:30556083-30556083;hs9:12665566-12665566,hs9:13117644-13117644;hs9:17654237-17654237,hs9:19771070-19771070;hs9:10321434-10321434,hs9:29595452-29595452;hs9:19104394-19104394,hs9:27734756-27734756;hs9:26413453-26413453,hs9:26756213-26756213 C9orf68;CDKN2A;JAK2;JMJD2C;KCNV2;KIAA1797;MLLT3;MPDZ;NFIB;SLC1A1;SMARCA2;TPD52L3 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes C9orf68,KIAA1797;JAK2,TPD52L3;MPDZ,NFIB;SLC1A1,JMJD2C;SMARCA2,KCNV2 CTDB0103 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 1 Synovial sarcoma Next Generation Sequencing Homo sapiens SW982 Illumina Genome Analyzer II Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes NA CTDB0104 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 11 Melanoma Next Generation Sequencing Homo sapiens SC32 Illumina Genome Analyzer II Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes NA CTDB0105 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 16 Glioblastoma Next Generation Sequencing Homo sapiens A172 Illumina Genome Analyzer II Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes NA CTDB0106 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 1,4,10,14 Pancreatic cancer Next Generation Sequencing Homo sapiens PD3646a Illumina Genome Analyzer II Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes NA CTDB0107 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 12,20 Osteosarcoma Next Generation Sequencing Homo sapiens PD3799a Illumina Genome Analyzer II hs12:58442187-58442187,hs12:57620230-57620230;hs12:57620497-57620497,hs12:58957976-58957976;hs20:7501303-7501303,hs20:43336042-43336042;hs12:57011311-57011311,hs12:57554249-57554249;hs12:67076643-67076943,hs12:67078090-67078390;hs20:2773550-2773550,hs20:23029205-23029205;hs20:17367251-17367251,hs20:21747854-21747854;hs12:64896001-64896001,hs12:67076811-67076811;hs12:66879952-66879952,hs12:73819282-73819282;hs12:59641861-59641861,hs12:59342711-59342711;hs12:59342779-59342779,hs12:68303999-68303999;hs12:37900026-37900026,hs12:57263787-57263787;hs12:38289239-38289239,hs12:38309029-38309029;hs20:25223958-25224258,hs20:52966624-52966924;hs20:52039440-52039440,hs20:60256737-60256737;hs12:65629910-65629910,hs12:66479252-66479252;hs12:66316446-66316446,hs12:74211707-74211707;hs12:67671294-67671294,hs12:69870130-69870130;hs20:21439646-21439946,hs20:22033696-22033996;hs20:17412002-17412002,hs20:50802396-50802396;hs12:58428539-58428839,hs12:66811518-66811818;hs12:65789899-65789899,hs12:73627618-73627618;hs12:58912619-58912619,hs12:66695126-66695126;hs12:56074829-56074829,hs12:66023883-66023883;hs12:57025231-57025231,hs12:70247750-70247750;hs12:55988628-55988628,hs12:58481314-58481314;hs12:57290916-57290916,hs12:69220231-69220231;hs12:68246320-68246320,hs12:65313009-65313009;hs12:65312973-65312973,hs12:68247450-68247450;hs20:34354393-34354393,hs20:43844955-43844955;hs12:66649897-66649897,hs12:70220390-70220390;hs12:39452938-39452938,hs12:67694878-67694878;hs12:55957687-55957687,hs12:67026716-67026716;hs12:65570296-65570296,hs12:67574938-67574938;hs20:59727255-59727255,hs20:59880825-59880825;hs20:47000736-47000736,hs20:55792873-55792873;hs12:39454856-39454856,hs12:56573381-56573381;hs20:7141982-7141982,hs20:31100556-31100556;hs12:60388899-60388899,hs12:66908919-66908919;hs12:65253483-65253483,hs12:67018446-67018446;hs12:69881026-69881026,hs12:70299595-70299595;hs12:64506231-64506531,hs12:70132255-70132555;hs12:64502447-64502747,hs12:67215504-67215804;hs12:37173408-37173408,hs12:57397386-57397386;hs12:57779502-57779502,hs12:73945700-73945700;hs12:37593874-37593874,hs12:58987651-58987651;hs12:59292511-59292511,hs12:67150585-67150585;hs12:60428880-60429180,hs12:69403640-69403940;hs12:67470416-67470716,hs12:67471539-67471839;hs12:60123239-60123239,hs12:66815116-66815116;hs20:23295971-23295971,hs20:43085308-43085308;hs12:40208112-40208112,hs12:55974495-55974495;hs12:39976799-39976799,hs12:65238670-65238670;hs20:20615726-20615726,hs20:38766439-38766439;hs12:66356997-66356997,hs12:67797477-67797477;hs12:39826082-39826082,hs12:65283127-65283127;hs12:66695545-66695545,hs12:67857536-67857536;hs12:59846330-59846330,hs12:68244402-68244402;hs12:40350865-40350865,hs12:66125080-66125080;hs12:56572643-56572643,hs12:57290007-57290007;hs12:40343752-40343752,hs12:66003117-66003117;hs12:40004615-40004615,hs12:73459440-73459440;hs12:56316123-56316123,hs12:59359795-59359795;hs12:57829380-57829380,hs12:66032035-66032035;hs12:67013937-67013937,hs12:73509415-73509415;hs12:56835299-56835299,hs12:58031479-58031479;hs12:57025146-57025446,hs12:70247553-70247853;hs20:48658235-48658235,hs20:59724130-59724130;hs12:66553441-66553441,hs12:69990363-69990363;hs20:34354352-34354652,hs20:43844786-43845086;hs12:40417611-40417611,hs12:68190511-68190511;hs12:37614161-37614161,hs12:65369721-65369721;hs12:64502447-64502747,hs12:67215504-67215804;hs12:75195155-75195155,hs12:75196750-75196750;hs12:57763521-57763521,hs12:68088382-68088382;hs20:44155408-44155408,hs20:46026329-46026329;hs12:66325398-66325398,hs12:67282959-67282959;hs12:66297342-66297342,hs12:68775855-68775855;hs20:17758396-17758396,hs20:61252776-61252776;hs12:37593936-37594236,hs12:58987599-58987899;hs12:38720447-38720447,hs12:67489340-67489340;hs12:57620431-57620431,hs12:58486346-58486346;hs12:57997044-57997044,hs12:67474026-67474026;hs20:52163530-52163530,hs20:53475058-53475058;hs20:12865832-12865832,hs20:52036066-52036066;hs12:38142661-38142661,hs12:38821302-38821302;hs12:57400320-57400320,hs12:74122877-74122877;hs20:2773142-2773442,hs20:23028901-23029201;hs12:65412680-65412680,hs12:67660836-67660836;hs20:17367052-17367352,hs20:21747809-21748109;hs12:60009145-60009145,hs12:66006029-66006029;hs12:64895742-64896042,hs12:67076821-67077121;hs12:57304371-57304371,hs12:65919665-65919665;hs12:39870405-39870405,hs12:74420235-74420235;hs12:55988642-55988642,hs12:58481060-58481360;hs12:56233854-56233854,hs12:68211530-68211530;hs20:59727302-59727602,hs20:59880557-59880857;hs20:7141866-7142166,hs20:31100419-31100719;hs12:64506231-64506531,hs12:70132255-70132555;hs12:59002439-59002439,hs12:69951395-69951395;hs20:38833017-38833017,hs20:45835704-45835704;hs12:56777639-56777639,hs12:57102652-57102652;hs12:37613230-37613230,hs12:70256621-70256621;hs12:70497500-70497500,hs12:73380213-73380213;hs12:67327766-67327766,hs12:73440723-73440723 GZF1;STK4 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes GZF1,STK4 CTDB0108 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 8,12,14 Osteosarcoma Next Generation Sequencing Homo sapiens PD3786a Illumina Genome Analyzer II hs3:118093916-118093916,hs3:118426816-118426816;hs4:177436270-177436270,hs22:32553886-32553886;hs5:14715569-14715569,hs17:31949191-31949191;hs7:69644187-69644187,hs7:69876978-69876978;hs8:3168052-3168052,hs8:3939631-3939631;hs8:3583877-3583877,hs14:50924581-50924581;hs8:3603627-3603627,hs14:36679515-36679515;hs8:3685593-3685593,hs14:34524805-34524805;hs8:4167645-4167645,hs14:33699490-33699490;hs8:5868740-5868740,hs14:52866436-52866436;hs8:6133331-6133331,hs8:6251428-6251428;hs8:6135587-6135587,hs14:52515435-52515435;hs8:6494155-6494155,hs8:6515408-6515408;hs8:8909506-8909506,hs8:21278604-21278604;hs8:9789525-9789525,hs8:11858135-11858135;hs8:9817353-9817353,hs8:11469184-11469184;hs8:9834568-9834568,hs8:17016047-17016047;hs8:10383750-10383750,hs8:14278669-14278669;hs8:10388325-10388325,hs8:10493176-10493176;hs8:10416024-10416024,hs8:11104659-11104659;hs8:10422441-10422441,hs8:17483930-17483930;hs8:10626797-10626797,hs8:21210586-21210586;hs8:10920388-10920388,hs8:16882348-16882348;hs8:10925607-10925607,hs8:17536211-17536211;hs8:11115284-11115284,hs8:13237022-13237022;hs8:11342940-11342940,hs8:17601844-17601844;hs8:11625722-11625722,hs8:11862030-11862030;hs8:11627133-11627133,hs14:37796212-37796212;hs8:12460390-12460390,hs8:21613065-21613065;hs8:13207928-13207928,hs8:21227969-21227969;hs8:13210727-13210727,hs8:13275530-13275530;hs8:13268473-13268473,hs8:17496360-17496360;hs8:16875456-16875456,hs8:21215670-21215670;hs8:20331966-20331966,hs8:20393586-20393586;hs8:21302938-21302938,hs14:26558249-26558249;hs8:91341238-91341238,hs8:141775822-141775822;hs8:141571747-141571747,hs12:16046949-16046949;hs8:142747126-142747126,hs12:16430865-16430865;hs8:142747678-142747678,hs12:16603247-16603247;hs8:142845370-142845370,hs8:143474860-143474860;hs8:144181010-144181010,hs12:3880124-3880124;hs9:129999857-129999857,hs9:130014062-130014062;hs10:112373403-112373403,hs19:17271609-17271609;hs10:112373452-112373452,hs22:34941910-34941910;hs12:1815281-1815281,hs12:12569624-12569624;hs12:4316907-4316907,hs14:102135076-102135076;hs12:8757731-8757731,hs12:8847883-8847883;hs12:9411021-9411021,hs14:27661974-27661974;hs12:10980072-10980072,hs12:30029899-30029899;hs12:11027103-11027103,hs14:102139231-102139231;hs12:11366981-11366981,hs14:94525195-94525195;hs12:12573054-12573054,hs12:30002256-30002256;hs12:12586928-12586928,hs14:102111610-102111610;hs12:12597865-12597865,hs14:99429192-99429192;hs12:12687540-12687540,hs12:14245323-14245323;hs12:14117741-14117741,hs12:14185562-14185562;hs12:16049923-16049923,hs12:17462418-17462418;hs12:16051037-16051037,hs12:23459482-23459482;hs12:16051062-16051062,hs12:17462804-17462804;hs12:16054806-16054806,hs12:16463017-16463017;hs12:16433142-16433142,hs12:16466398-16466398;hs12:16436484-16436484,hs12:23822360-23822360;hs12:20337069-20337069,hs16:9621049-9621049;hs12:29963884-29963884,hs14:96813809-96813809;hs12:30014548-30014548,hs14:99450969-99450969;hs12:69443870-69443870,hs12:94616586-94616586;hs12:69528086-69528086,hs12:96433506-96433506;hs12:95629192-95629192,hs12:96135863-96135863;hs12:95909413-95909413,hs12:96157768-96157768;hs14:26550303-26550303,hs14:26587979-26587979;hs14:27664758-27664758,hs14:54170365-54170365;hs14:27671101-27671101,hs14:37793569-37793569;hs14:28723349-28723349,hs14:28745622-28745622;hs14:28743412-28743412,hs14:36721446-36721446;hs14:28753669-28753669,hs14:47494643-47494643;hs14:28767333-28767333,hs14:47493254-47493254;hs14:28957683-28957683,hs14:43733199-43733199;hs14:33697734-33697734,hs14:33700245-33700245;hs14:34525615-34525615,hs14:50800669-50800669;hs14:36632961-36632961,hs14:49464699-49464699;hs14:36752027-36752027,hs14:42844674-42844674;hs14:40070726-40070726,hs14:50931706-50931706;hs14:48806826-48806826,hs14:50956419-50956419;hs14:50974535-50974535,hs14:93501647-93501647;hs14:51140501-51140501,hs14:52932863-52932863;hs14:51343897-51343897,hs14:90906379-90906379;hs14:53076409-53076409,hs14:90957960-90957960;hs14:90870347-90870347,hs14:90957576-90957576;hs14:90906448-90906448,hs14:90906383-90906383;hs14:96798857-96798857,hs14:102080242-102080242;hs16:5520573-5520573,hs16:6093705-6093705;hs16:6184030-6184030,hs16:6185476-6185476;hs16:6244340-6244340,hs16:20556910-20556910;hs16:7089113-7089113,hs16:7739957-7739957;hs16:7906912-7906912,hs16:32551273-32551273;hs16:20340850-20340850,hs16:25864734-25864734;hs17:3356980-3356980,hs17:19605371-19605371;hs17:4646185-4646185,hs17:15822489-15822489;hs17:15819233-15819233,hs17:19182180-19182180;hs17:17634699-17634699,hs20:44505837-44505837;hs17:19604264-19604264,hs20:44548966-44548966;hs17:41558942-41558942,hs22:34941922-34941922;hs18:10824696-10824696,hs18:51654932-51654932;hs18:10824697-10824697,hs18:10824728-10824728;hs18:35339189-35339189,hs18:35392785-35392785;hs18:49622225-49622225,hs20:32287220-32287220;hs18:64755617-64755617,hs18:65131219-65131219;hs20:29299369-29299369,hs20:32231405-32231405;hs20:44418631-44418631,hs20:44545380-44545380;hs22:32554028-32554028,hs4:177585285-177585285;hsY:8187550-8187550,hsY:8189429-8189429;hs12:4357009-4357009,hs12:10955611-10955611;hs8:10630023-10630323,hs8:11595592-11595892;hs8:9790035-9790335,hs8:21229839-21230139;hs14:33108356-33108656,hs14:34528126-34528426;hs12:29986214-29986214,hs14:102097072-102097072;hs12:90631856-90632156,hs12:94612735-94613035 Q6ZP57_HUMAN;GFRA2 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes Q6ZP57_HUMAN,GFRA2 CTDB0109 Research 21215367 Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, M Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 2011 Jan 7,9,12,13 Osteosarcoma Next Generation Sequencing Homo sapiens PD3791a Illumina Genome Analyzer II hs13:59499579-59499579,hs13:82915974-82915974;hs21:30622804-30622804,hs21:30634524-30634524;hs13:77097904-77097904,hs13:94876739-94876739;hs8:135611010-135611010,hs8:135762196-135762196;hs7:17553972-17553972,hs7:35734706-35734706;hs13:60955586-60955586,hs13:82714826-82714826;hs13:48205283-48205283,hs13:50150066-50150066;hs7:69785170-69785170,hs7:69874968-69874968;hs5:176893660-176893660,hs5:176952466-176952466;hs7:15578703-15578703,hs7:34543166-34543166;hs13:78597797-78597797,hs13:79236995-79236995;hs13:82714808-82714808,hs13:84088098-84088098;hs7:15570337-15570337,hs9:131506924-131506924;hs7:33158940-33158940,hs13:100442204-100442204;hs9:131022073-131022073,hs12:12982393-12982393;hs7:15568375-15568375,hs13:48072900-48072900;hs7:17553579-17553579,hs13:81855713-81855713;hs7:34373151-34373151,hs13:82810817-82810817;hs9:130352994-130352994,hs12:11686468-11686468;hs7:15578929-15578929,hs13:107501387-107501387;hs7:35987789-35987789,hs13:56881282-56881282;hs7:34005998-34005998,hs13:48900633-48900633;hs7:34317837-34317837,hs13:49109337-49109337;hs9:130949365-130949365,hs13:84216848-84216848;hs9:131526566-131526566,hs13:48780919-48780919;hs17:7835375-7835375,hs17:7848044-7848044;hs8:48530501-48530501,hs8:70657533-70657533;hs13:60925213-60925213,hs13:82968411-82968411;hs13:84755845-84755845,hs13:92223455-92223455;hs13:43974978-43974978,hs13:82820285-82820285;hs4:11022842-11022842,hs4:11336969-11336969;hs8:86571587-86571587,hs8:97625240-97625240;hs13:102720277-102720277,hs13:103442443-103442443;hs13:81765610-81765610,hs13:85422486-85422486;hs13:87073096-87073096,hs13:87597947-87597947;hs8:84069743-84069743,hs8:103185573-103185573;hs13:31438240-31438240,hs13:49129602-49129602;hs13:49121696-49121696,hs13:56881285-56881285;hs8:80283311-80283311,hs8:119951058-119951058;hs13:78986804-78986804,hs13:92854589-92854589;hs13:84223964-84223964,hs13:89446785-89446785;hs7:15392876-15392876,hs7:16002674-16002674;hs13:83182133-83182133,hs13:84909048-84909048;hs13:84211057-84211057,hs13:92634637-92634637;hs10:15522819-15522819,hs10:15581536-15581536;hs17:7816821-7816821,hs17:7871527-7871527;hs8:68122659-68122659,hs8:92203315-92203315;hs2:5785041-5785341,hs2:5864425-5864725;hs5:14646093-14646393,hs5:14855324-14855624;hs6:71196895-71196895,hs6:71233346-71233346;hs7:17128705-17129005,hs13:101720860-101721160;hs7:17545091-17545091,hs9:130959968-130959968;hs7:17561816-17562116,hs13:49038306-49038606;hs7:17715498-17715498,hs7:34743376-34743376;hs7:33166625-33166625,hs13:84769984-84769984;hs7:34318132-34318132,hs13:84082986-84082986;hs7:34435925-34435925,hs7:35821800-35821800;hs7:34445925-34445925,hs13:94901467-94901467;hs7:34751314-34751614,hs13:83387061-83387361;hs7:35452585-35452585,hs13:48086547-48086547;hs7:35461291-35461291,hs13:83511816-83511816;hs7:35821965-35821965,hs13:50109227-50109227;hs7:36323243-36323243,hs13:49415266-49415266;hs7:36325447-36325447,hs13:95750937-95750937;hs8:10319985-10319985,hs8:72336297-72336297;hs8:10627693-10627693,hs8:19900359-19900359;hs8:15264001-15264001,hs8:48514905-48514905;hs8:17254278-17254278,hs8:84925287-84925287;hs8:19935905-19935905,hs8:105748022-105748022;hs8:21975069-21975069,hs8:84528700-84528700;hs8:49662696-49662696,hs8:125935980-125935980;hs8:89617303-89617303,hs8:95342668-95342668;hs8:93948443-93948443,hs8:102986476-102986476;hs8:131065144-131065144,hs8:131216815-131216815;hs9:130948824-130948824,hs13:48089482-48089482;hs10:80680600-80680600,hs10:80806585-80806585;hs11:85062165-85062165,hs11:85134471-85134471;hs11:69623478-69623778,hs11:69805619-69805919;hs12:11668570-11668570,hs13:92225461-92225461;hs13:31438241-31438241,hs13:49121691-49121691;hs13:41774644-41774644,hs13:85405618-85405618;hs13:43965419-43965419,hs13:52397246-52397246;hs13:43974532-43974532,hs13:49312362-49312362;hs13:44454294-44454294,hs13:48921870-48921870;hs13:47966014-47966014,hs13:95733556-95733556;hs13:48093779-48093779,hs13:94426410-94426410;hs13:48780835-48781135,hs13:80597813-80598113;hs13:48900350-48900350,hs13:82993208-82993208;hs13:48982947-48982947,hs13:107521925-107521925;hs13:49000163-49000163,hs13:81941909-81941909;hs13:49067280-49067280,hs13:56844933-56844933;hs13:49129599-49129599,hs13:78642773-78642773;hs13:49420650-49420650,hs13:56903507-56903507;hs13:50149573-50149573,hs13:92024874-92024874;hs13:92024822-92024822,hs13:92024888-92024888;hs13:50554976-50554976,hs13:89486704-89486704;hs13:60895207-60895207,hs13:84029239-84029239;hs13:65952585-65952585,hs13:77959707-77959707;hs13:73123219-73123219,hs13:94769714-94769714;hs13:74562077-74562077,hs13:84886089-84886089;hs13:76772706-76772706,hs13:81872343-81872343;hs13:77076546-77076846,hs13:82934400-82934700;hs13:80570746-80570746,hs13:103342070-103342070;hs13:80600527-80600527,hs13:89064951-89064951;hs13:83830407-83830407,hs13:84046864-84046864;hs13:84046794-84046794,hs13:84881848-84881848;hs13:84773871-84773871,hs13:94876655-94876655;hs13:86636203-86636203,hs13:94901020-94901020;hs13:89050628-89050628,hs13:90372387-90372387;hs13:92186056-92186056,hs13:92272100-92272100;hs13:49020561-49020861,hs13:94460207-94460507;hs13:61466108-61466408,hs13:89045402-89045702;hs7:34050050-34050350,hs7:35417964-35418264;hs13:50146435-50146735,hs13:59499522-59499822 SPTAN1;ETV6 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ~25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer. NCBI 36/hg18 Yes SPTAN1,ETV6 CTDB0113 Research 22265402 Rausch T, Jones DT, Zapatka M, Stutz AM, Zichner T, Weischenfeldt J, Jager N, Remke M, Shih D, Northcott PA, Pfaff E, Tica J, Wang Q, Massimi L, Witt H, Bender S, Pleier S, Cin H, Hawkins C, Beck C, von Deimling A, Hans V, Brors B, Eils R, Scheurlen W, Bl Genome Sequencing of Pediatric Medulloblastoma Links Catastrophic DNA Rearrangements with TP53 Mutations Cell 2012 Jan 3,4,14 Sonic-Hedgehog medulloblastoma Next Generation Sequencing Homo sapiens LFS-MB1 Illumina HiSeq 2000 chr1:63444401-63528602:-1;chr3:113498368-130583576:-1;chr4:124191414-164362015:-1;chr4:164458233-175842161:-1;chr8:3492450-3852149:-1;chr12:11191764-11292955:-1;chr12:33535367-33818924:-1;chr14:106815470-107130874:-1;chr4:124098068-124191394:1;chr4:159597606-159858310:1;chr4:164362032-164458144:1;chr4:170360650-170395000:1;chr4:171723347-171841028:1;chr4:175842203-176109339:1;chr14:20664952-20670397:1;chr14:22803240-22833959:1;chr14:79925792-80106000:1;chr14:80115001-80144983:1;chr14:80230194-80311870:1;chr2:14216912-16903663:1;chr3:112938115-113498342:1;chr3:130583569-131022000:1;chr3:139617001-141173250:1 hs4:159858310-159858310,hs14:79925792-79925792;hs4:170360650-170360650,hs14:22803240-22803240;hs4:176109339-176109339,hs14:80230194-80230194;hs4:171723347-171723347,hs14:20670397-20670397;hs11:38226283-38226283,hs17:16021393-16021393;hs13:50502098-50502098,hs18:70220182-70220182;hs1:179666590-179666590,hs1:182191375-182191375;hs2:14216833-14216833,hs2:16903720-16903720;hs2:115961657-115961657,hs2:120963994-120963994;hs2:116503651-116503651,hs2:207025403-207025403;hs2:120596559-120596559,hs2:122113238-122113238;hs2:120610969-120610969,hs2:183771998-183771998;hs2:121087792-121087792,hs2:121835816-121835816;hs2:183737296-183737296,hs2:200282232-200282232;hs3:112938044-112938044,hs3:141173305-141173305;hs3:131021629-131021629,hs3:139858259-139858259;hs3:139616963-139616963,hs3:139858020-139858020;hs4:116681164-116681164,hs4:127291493-127291493;hs4:116953341-116953341,hs4:164151091-164151091;hs4:124098007-124098007,hs4:170394907-170394907;hs4:124543475-124543475,hs4:164588491-164588491;hs4:128368058-128368058,hs4:170025020-170025020;hs4:159597587-159597587,hs4:171841070-171841070;hs4:164803329-164803329,hs4:170426855-170426855;hs7:64763921-64763921,hs7:66469133-66469133;hs10:13089870-13089870,hs10:50289722-50289722;hs10:29054168-29054168,hs10:62557463-62557463;hs10:48429595-48429595,hs10:49919974-49919974;hs11:38614205-38614205,hs11:38855827-38855827;hs11:38615134-38615134,hs11:41317169-41317169;hs11:41577279-41577279,hs11:43868468-43868468;hs14:20664900-20664900,hs14:80311910-80311910;hs16:21667732-21667732,hs16:24069189-24069189;hs22:21317195-21317195,hs22:21398564-21398564;hsX:49210465-49210465,hsX:49366877-49366877 ADAM29;ANAPC10;BOC;FBXW7;GAB1;GLI2;GRIA2;GYPA;GYPB;IL15;MYCN;NEK11;PPP2R2C;TRIM2;WDR17 European Molecular Biology Laboratory, Meyerhofstr. 1, 69117 Heidelberg, Germany Genomic rearrangements are thought to occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving massive chromosome rearrangements in a one-step catastrophic event termed chromothripsis. We report the whole-genome sequencing-based analysis of a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome), uncovering massive, complex chromosome rearrangements. Integrating TP53 status with microarray and deep sequencing-based DNA rearrangement data in additional patients reveals a striking association between TP53 mutation and chromothripsis in SHH-MBs. Analysis of additional tumor entities substantiates a link between TP53 mutation and chromothripsis, and indicates a context-specific role for p53 in catastrophic DNA rearrangements. Among these, we observed a strong association between somatic TP53 mutations and chromothripsis in acute myeloid leukemia. These findings connect p53 status and chromothripsis in specific tumor types, providing a genetic basis for understanding particularly aggressive subtypes of cancer. GRCh37/hg19 GSE14437;GSE32462;GSE19101;GSE23452;GSE34323;GSE34258 EGAS00001000085 Yes NA CTDB0114 Research 22265402 Rausch T, Jones DT, Zapatka M, Stutz AM, Zichner T, Weischenfeldt J, Jager N, Remke M, Shih D, Northcott PA, Pfaff E, Tica J, Wang Q, Massimi L, Witt H, Bender S, Pleier S, Cin H, Hawkins C, Beck C, von Deimling A, Hans V, Brors B, Eils R, Scheurlen W, Bl Genome Sequencing of Pediatric Medulloblastoma Links Catastrophic DNA Rearrangements with TP53 Mutations Cell 2012 Jan 3,8,17,X Sonic-Hedgehog medulloblastoma Next Generation Sequencing Homo sapiens LFS-MB2 Illumina HiSeq 2000 chr4:188409906-189503084:-1;chr5:5922885-14314337:-1;chr5:50792381-98447862:-1;chr6:29911431-30228533:-1;chr7:90522308-90588071:-1;chr7:90612330-92469025:-1;chr7:91376469-92127901:-1;chr8:1875838-10722429:-1;chr8:9629722-17109168:-1;chr11:23172601-24575386:-1;chr17:48871254-48940606:-1;chr18:45077868-56806980:-1;chr19:13623874-15447939:-1;chr19:16494334-16994600:-1;chrX:117637014-120303308:-1;chrX:121432913-130860060:-1 hs2:50943844-50943844,hs2:51065148-51065148;hs3:4984736-4984736,hs3:36349735-36349735;hs4:189232547-189232547,hs4:189534830-189534830;hs5:1410207-1410207,hs5:103772276-103772276;hs5:5889265-5889265,hs5:14348517-14348517;hs5:54107033-54107033,hs5:96117539-96117539;hs5:56540227-56540227,hs5:103054335-103054335;hs5:99317512-99317512,hs5:104095025-104095025;hs7:90471247-90471247,hs7:105787298-105787298;hs7:90560959-90560959,hs7:106086607-106086607;hs7:90640706-90640706,hs7:90768468-90768468;hs7:90715844-90715844,hs7:91497552-91497552;hs7:90724457-90724457,hs7:106482610-106482610;hs7:90998372-90998372,hs7:105987011-105987011;hs7:91026730-91026730,hs7:92130470-92130470;hs7:91560973-91560973,hs7:106105823-106105823;hs7:91663486-91663486,hs7:92128327-92128327;hs7:91778926-91778926,hs7:92229681-92229681;hs7:91791410-91791410,hs7:92473297-92473297;hs7:91803566-91803566,hs7:92030918-92030918;hs7:92351343-92351343,hs7:105896877-105896877;hs7:92381639-92381639,hs7:92557144-92557144;hs7:92845067-92845067,hs7:106761774-106761774;hs7:129677752-129677752,hs7:132312507-132312507;hs8:9650762-9650762,hs8:15733400-15733400;hs8:9695585-9695585,hs8:16544505-16544505;hs8:10501739-10501739,hs8:66488505-66488505;hs8:16553290-16553290,hs8:48957757-48957757;hs8:17075594-17075594,hs8:66502400-66502400;hs8:28076906-28076906,hs8:66479399-66479399;hs8:42678552-42678552,hs8:75717941-75717941;hs8:48957507-48957507,hs8:68047639-68047639;hs17:15853987-15853987,hs17:54957986-54957986;hs17:26743059-26743059,hs17:27067877-27067877;hs17:27079023-27079023,hs17:55022936-55022936;hs17:31921782-31921782,hs17:43403969-43403969;hs17:32772969-32772969,hs17:32879681-32879681;hs17:50402026-50402026,hs17:55210345-55210345;hs17:55164797-55164797,hs17:64399654-64399654;hs17:57571985-57571985,hs17:58356131-58356131;hs18:40529221-40529221,hs18:44778253-44778253;hs18:40723689-40723689,hs18:43436945-43436945;hs18:40845756-40845756,hs18:41443431-41443431;hs18:41968741-41968741,hs18:42887677-42887677;hs18:42896239-42896239,hs18:44486476-44486476;hs18:43443538-43443538,hs18:44140503-44140503;hs19:53362609-53362609,hs19:53969645-53969645;hsX:2833855-2833855,hsX:78605776-78605776;hsX:65918786-65918786,hsX:136944645-136944645;hsX:71079504-71079504,hsX:91194619-91194619;hsX:73782637-73782637,hsX:87033199-87033199;hsX:73825461-73825461,hsX:73890151-73890151;hsX:73833598-73833598,hsX:106515760-106515760;hsX:87062791-87062791,hsX:127534168-127534168;hsX:91212287-91212287,hsX:92107029-92107029;hsX:92000657-92000657,hsX:127505080-127505080;hsX:93878280-93878280,hsX:119920717-119920717;hsX:120424739-120424739,hsX:149004603-149004603;hsX:121407933-121407933,hsX:133389821-133389821;hs3:3865919-3865919,hsX:121844920-121844920;hs12:34841679-34841679,hs8:46872792-46872792;hs12:34841679-34841679,hs19:27752864-27752864;hs20:26318595-26318595,hs5:46346297-46346297;hs20:26318603-26318603,hsX:130893215-130893215;hsX:106556626-106556626,hs3:3588416-3588416;hsX:121804642-121804642,hs12:32269547-32269547;hsX:121947652-121947652,hs3:36334979-36334979;hsX:133358177-133358177,hs3:4932716-4932716 CDK6;DCX;DDX3X;GLI2;FOXO4;MAGEA1;MYCN;NAMPT;TAF1 European Molecular Biology Laboratory, Meyerhofstr. 1, 69117 Heidelberg, Germany Genomic rearrangements are thought to occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving massive chromosome rearrangements in a one-step catastrophic event termed chromothripsis. We report the whole-genome sequencing-based analysis of a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome), uncovering massive, complex chromosome rearrangements. Integrating TP53 status with microarray and deep sequencing-based DNA rearrangement data in additional patients reveals a striking association between TP53 mutation and chromothripsis in SHH-MBs. Analysis of additional tumor entities substantiates a link between TP53 mutation and chromothripsis, and indicates a context-specific role for p53 in catastrophic DNA rearrangements. Among these, we observed a strong association between somatic TP53 mutations and chromothripsis in acute myeloid leukemia. These findings connect p53 status and chromothripsis in specific tumor types, providing a genetic basis for understanding particularly aggressive subtypes of cancer. GRCh37/hg19 GSE14437;GSE32462;GSE19101;GSE23452;GSE34323;GSE34258 EGAS00001000085 Yes NAMPT,CDK6 CTDB0115 Research 22265402 Rausch T, Jones DT, Zapatka M, Stutz AM, Zichner T, Weischenfeldt J, Jager N, Remke M, Shih D, Northcott PA, Pfaff E, Tica J, Wang Q, Massimi L, Witt H, Bender S, Pleier S, Cin H, Hawkins C, Beck C, von Deimling A, Hans V, Brors B, Eils R, Scheurlen W, Bl Genome Sequencing of Pediatric Medulloblastoma Links Catastrophic DNA Rearrangements with TP53 Mutations Cell 2012 Jan 3,15 Sonic-Hedgehog medulloblastoma Next Generation Sequencing Homo sapiens LFS-MB3 Illumina HiSeq 2000 chr1:81896744-82117509:-1;chr1:145079866-145189859:-1;chr2:110109313-110251287:-1;chr2:149690639-149790578:-1;chr2:233210308-233318177:-1;chr3:129535039-142240426:-1;chr4:867271-1581792:-1;chr4:18285761-96336487:-1;chr4:18414602-28991025:-1;chr4:134478891-166432306:-1;chr5:180375000-180432033:-1;chr6:152778995-152955408:-1;chr7:2153486-15038940:-1;chr7:56564619-57477969:-1;chr8:35121733-35291026:-1;chr12:17722945-30145481:-1;chr13:114325887-114426023:-1;chr15:25626015-35404817:-1;chr15:27592310-88731192:-1;chr15:27592381-50831447:-1;chr15:27638165-65034324:-1;chr15:27692334-35404806:-1;chr15:27692341-34751965:-1;chr15:28025119-29058591:-1;chr15:29564215-31973108:-1;chr15:34028982-84374758:-1;chr15:34602258-66226936:-1;chr15:34752392-35404837:-1;chr15:35405071-47542305:-1;chr15:35405083-60559493:-1;chr15:35405921-89774781:-1;chr15:35405943-56590661:-1;chr15:35406062-47784193:-1;chr15:35406068-61425482:-1;chr15:36048000-38826328:-1;chr15:36079877-62499897:-1;chr15:36141398-77852311:-1;chr15:38019644-85778959:-1;chr15:38354283-38856739:-1;chr15:38963868-55081326:-1;chr15:41476300-54247872:-1;chr15:41612473-84028139:-1;chr15:43080211-81247110:-1;chr15:44785584-82339510:-1;chr15:45265673-51715441:-1;chr15:45497532-67049070:-1;chr15:47535310-96255463:-1;chr15:47676606-92567896:-1;chr15:47845948-55080236:-1;chr15:49628274-59475290:-1;chr15:50108383-87670940:-1;chr15:50798716-101663200:-1;chr15:50813733-66438292:-1;chr15:50824388-63715435:-1;chr15:50833651-88731133:-1;chr15:56406665-100282989:-1;chr15:56614544-62885408:-1;chr15:57103408-58691682:-1;chr15:58386821-84945701:-1;chr15:60122494-88782529:-1;chr15:62784551-69024995:-1;chr15:64448240-87886231:-1;chr15:65433008-101841362:-1;chr15:66242159-93836383:-1;chr15:66836685-86095274:-1;chr15:70301222-92712797:-1;chr15:73600835-100160977:-1;chr15:75498764-76064634:-1;chr15:89416605-91127851:-1;chr18:75721727-75772072:-1;chr21:41468328-44066701:-1;chr21:42955522-43005639:-1;chrY:14440191-15234430:-1;chr15:37593001-37809000:1;chr15:44509001-44786000:1;chr15:46078001-47139000:1;chr15:54279001-54476000:1;chr15:65861001-65933000:1;chr15:66497001-66691000:1;chr15:77636001-77848000:1;chr15:79825001-79979000:1;chr15:82339001-83057580:1;chr15:85315001-85611000:1;chr15:99055001-100149000:1;chr2:13598001-17621000:1 hs1:78170570-78170570,hs1:79568682-79568682;hs1:78990540-78990540,hs1:83363860-83363860;hs2:13598087-13598087,hs2:17620755-17620755;hs2:170355427-170355427,hs2:170478847-170478847;hs3:53898723-53898723,hs3:53981596-53981596;hs4:1600174-1600174,hs4:21569204-21569204;hs4:1648566-1648566,hs4:1772823-1772823;hs4:1759629-1759629,hs4:2041362-2041362;hs4:18415910-18415910,hs4:31101146-31101146;hs4:19044222-19044222,hs4:23704174-23704174;hs4:21765873-21765873,hs4:23062496-23062496;hs4:21807855-21807855,hs4:22714648-22714648;hs4:22617210-22617210,hs4:22715322-22715322;hs4:24718977-24718977,hs4:25400304-25400304;hs4:24732441-24732441,hs4:30095895-30095895;hs4:101974096-101974096,hs4:139906781-139906781;hs5:176195896-176195896,hs5:176406025-176406025;hs6:64338556-64338556,hs6:105479874-105479874;hs6:157609433-157609433,hs6:157691407-157691407;hs7:1146265-1146265,hs7:8133233-8133233;hs7:1149649-1149649,hs7:7800358-7800358;hs7:6529998-6529998,hs7:18228910-18228910;hs7:15171873-15171873,hs7:26191860-26191860;hs7:61056588-61056588,hs7:61675249-61675249;hs9:84926330-84926330,hs9:85100582-85100582;hs9:99381288-99381288,hs9:99638918-99638918;hs9:112209390-112209390,hs9:112344043-112344043;hs12:2387147-2387147,hs12:6705540-6705540;hs15:23291122-23291122,hs15:33806523-33806523;hs15:24850022-24850022,hs15:39119625-39119625;hs15:25312632-25312632,hs15:96150563-96150563;hs15:25625740-25625740,hs15:35406091-35406091;hs15:25990006-25990006,hs15:68635056-68635056;hs15:26026945-26026945,hs15:33183012-33183012;hs15:26031340-26031340,hs15:78474256-78474256;hs15:26129574-26129574,hs15:39873798-39873798;hs15:26683575-26683575,hs15:68950551-68950551;hs15:26941413-26941413,hs15:73072495-73072495;hs15:27176088-27176088,hs15:73397401-73397401;hs15:27475815-27475815,hs15:40752573-40752573;hs15:27692074-27692074,hs15:35406067-35406067;hs15:27692092-27692092,hs15:35404831-35404831;hs15:27692336-27692336,hs15:35406053-35406053;hs15:27829421-27829421,hs15:79452789-79452789;hs15:27910654-27910654,hs15:35427659-35427659;hs15:27911295-27911295,hs15:35405121-35405121;hs15:27987635-27987635,hs15:51025797-51025797;hs15:28262125-28262125,hs15:66438978-66438978;hs15:29363291-29363291,hs15:34721143-34721143;hs15:29932964-29932964,hs15:60131426-60131426;hs15:30357629-30357629,hs15:54269262-54269262;hs15:30935070-30935070,hs15:67256394-67256394;hs15:32195355-32195355,hs15:48516453-48516453;hs15:33145274-33145274,hs15:60373138-60373138;hs15:33153560-33153560,hs15:45617574-45617574;hs15:33814655-33814655,hs15:60454777-60454777;hs15:33840954-33840954,hs15:95576509-95576509;hs15:33987983-33987983,hs15:36878965-36878965;hs15:34082813-34082813,hs15:90796798-90796798;hs15:34154892-34154892,hs15:73178927-73178927;hs15:34468710-34468710,hs15:40627785-40627785;hs15:34502180-34502180,hs15:51315095-51315095;hs15:34619363-34619363,hs15:64049806-64049806;hs15:34622138-34622138,hs15:83813691-83813691;hs15:34729937-34729937,hs15:45503931-45503931;hs15:34751851-34751851,hs15:35406002-35406002;hs15:34752371-34752371,hs15:35405905-35405905;hs15:35404736-35404736,hs15:60558835-60558835;hs15:35404789-35404789,hs15:70940097-70940097;hs15:35404814-35404814,hs15:61426078-61426078;hs15:35404815-35404815,hs15:70940648-70940648;hs15:35404825-35404825,hs15:89775335-89775335;hs15:35404831-35404831,hs15:59448238-59448238;hs15:35404849-35404849,hs15:61425683-61425683;hs15:35404857-35404857,hs15:100706389-100706389;hs15:35404875-35404875,hs15:60560315-60560315;hs15:35404885-35404885,hs15:89775080-89775080;hs15:35404925-35404925,hs15:77221222-77221222;hs15:35405087-35405087,hs15:70940383-70940383;hs15:35405135-35405135,hs15:89775349-89775349;hs15:35405769-35405769,hs15:61426368-61426368;hs15:35405784-35405784,hs15:36138923-36138923;hs15:35405983-35405983,hs15:59449651-59449651;hs15:35780609-35780609,hs15:55111928-55111928;hs15:35861797-35861797,hs15:56736133-56736133;hs15:35871338-35871338,hs15:36055662-36055662;hs15:35872759-35872759,hs15:77219970-77219970;hs15:35946279-35946279,hs15:39625317-39625317;hs15:36017234-36017234,hs15:89363570-89363570;hs15:36053667-36053667,hs15:77221533-77221533;hs15:36118882-36118882,hs15:47779645-47779645;hs15:36382985-36382985,hs15:46238874-46238874;hs15:36503922-36503922,hs15:75229477-75229477;hs15:36612312-36612312,hs15:60831312-60831312;hs15:36628960-36628960,hs15:41096490-41096490;hs15:36653681-36653681,hs15:58832549-58832549;hs15:37014317-37014317,hs15:45958499-45958499;hs15:37031361-37031361,hs15:52399652-52399652;hs15:37388236-37388236,hs15:69153588-69153588;hs15:37418477-37418477,hs15:71350766-71350766;hs15:37432987-37432987,hs15:64735184-64735184;hs15:37809334-37809334,hs15:77848443-77848443;hs15:37836056-37836056,hs15:84594945-84594945;hs15:38159389-38159389,hs15:70274546-70274546;hs15:38684272-38684272,hs15:90729145-90729145;hs15:38846855-38846855,hs15:93561908-93561908;hs15:38864400-38864400,hs15:53641537-53641537;hs15:38954553-38954553,hs15:58247087-58247087;hs15:38962084-38962084,hs15:85078749-85078749;hs15:38963054-38963054,hs15:73186299-73186299;hs15:39133532-39133532,hs15:58506593-58506593;hs15:39259876-39259876,hs15:72246421-72246421;hs15:40999069-40999069,hs15:53607843-53607843;hs15:41370374-41370374,hs15:66326257-66326257;hs15:41405752-41405752,hs15:42953730-42953730;hs15:42435591-42435591,hs15:70007242-70007242;hs15:42439200-42439200,hs15:69956780-69956780;hs15:43209318-43209318,hs15:58613496-58613496;hs15:43310477-43310477,hs15:70270005-70270005;hs15:43350415-43350415,hs15:73145272-73145272;hs15:43375886-43375886,hs15:66031957-66031957;hs15:44225381-44225381,hs15:44508286-44508286;hs15:44306895-44306895,hs15:79824630-79824630;hs15:45127457-45127457,hs15:69637985-69637985;hs15:45274375-45274375,hs15:66035687-66035687;hs15:45283104-45283104,hs15:52816846-52816846;hs15:45613779-45613779,hs15:64077324-64077324;hs15:46078315-46078315,hs15:54476292-54476292;hs15:46950144-46950144,hs15:85617844-85617844;hs15:48255718-48255718,hs15:80162135-80162135;hs15:49109069-49109069,hs15:79585854-79585854;hs15:49638678-49638678,hs15:73127112-73127112;hs15:49890667-49890667,hs15:59180981-59180981;hs15:50106458-50106458,hs15:77997807-77997807;hs15:50366818-50366818,hs15:101988899-101988899;hs15:50930768-50930768,hs15:58529534-58529534;hs15:50932677-50932677,hs15:64809294-64809294;hs15:50943686-50943686,hs15:57194491-57194491;hs15:51116589-51116589,hs15:55100352-55100352;hs15:51417905-51417905,hs15:85311289-85311289;hs15:52406485-52406485,hs15:61708906-61708906;hs15:53485486-53485486,hs15:77997806-77997806;hs15:53937369-53937369,hs15:67394573-67394573;hs15:55279105-55279105,hs15:66736548-66736548;hs15:55518789-55518789,hs15:64729605-64729605;hs15:55519840-55519840,hs15:58532281-58532281;hs15:55852130-55852130,hs15:56412158-56412158;hs15:56396912-56396912,hs15:71170495-71170495;hs15:56414478-56414478,hs15:59451576-59451576;hs15:56589279-56589279,hs15:72230051-72230051;hs15:56618980-56618980,hs15:63463499-63463499;hs15:56781908-56781908,hs15:92825273-92825273;hs15:57115053-57115053,hs15:101197887-101197887;hs15:57572670-57572670,hs15:84934042-84934042;hs15:58779827-58779827,hs15:78087289-78087289;hs15:58870963-58870963,hs15:96457909-96457909;hs15:59385332-59385332,hs15:86865832-86865832;hs15:59450259-59450259,hs15:77922881-77922881;hs15:59724596-59724596,hs15:63026066-63026066;hs15:59738044-59738044,hs15:96911558-96911558;hs15:59844939-59844939,hs15:63224567-63224567;hs15:60186676-60186676,hs15:76959841-76959841;hs15:60193746-60193746,hs15:98024518-98024518;hs15:60297895-60297895,hs15:69088182-69088182;hs15:60309233-60309233,hs15:74707518-74707518;hs15:60423391-60423391,hs15:62843905-62843905;hs15:60560245-60560245,hs15:95019370-95019370;hs15:61341703-61341703,hs15:99030243-99030243;hs15:61617109-61617109,hs15:98831850-98831850;hs15:61718256-61718256,hs15:94646657-94646657;hs15:61832376-61832376,hs15:96679924-96679924;hs15:62748599-62748599,hs15:63389467-63389467;hs15:62841901-62841901,hs15:79316775-79316775;hs15:63170154-63170154,hs15:76256967-76256967;hs15:63259367-63259367,hs15:63524544-63524544;hs15:63383602-63383602,hs15:98835219-98835219;hs15:63924925-63924925,hs15:94534281-94534281;hs15:64401439-64401439,hs15:75128205-75128205;hs15:64447707-64447707,hs15:82306099-82306099;hs15:65457219-65457219,hs15:78548848-78548848;hs15:65734812-65734812,hs15:91148442-91148442;hs15:66497252-66497252,hs15:85611334-85611334;hs15:66691129-66691129,hs15:79979275-79979275;hs15:66699347-66699347,hs15:79208023-79208023;hs15:66752080-66752080,hs15:69097083-69097083;hs15:66963791-66963791,hs15:76059788-76059788;hs15:67399798-67399798,hs15:94652015-94652015;hs15:68342967-68342967,hs15:87938083-87938083;hs15:69138855-69138855,hs15:80649748-80649748;hs15:69480132-69480132,hs15:88773166-88773166;hs15:70134775-70134775,hs15:76288348-76288348;hs15:71368333-71368333,hs15:79320292-79320292;hs15:72794376-72794376,hs15:77285193-77285193;hs15:73610739-73610739,hs15:94445755-94445755;hs15:75409148-75409148,hs15:97267786-97267786;hs15:76263449-76263449,hs15:87174663-87174663;hs15:76614577-76614577,hs15:87495664-87495664;hs15:77930005-77930005,hs15:93151352-93151352;hs15:77996565-77996565,hs15:87673112-87673112;hs15:80152408-80152408,hs15:102145023-102145023;hs15:82303408-82303408,hs15:87886874-87886874;hs15:86078634-86078634,hs15:87814980-87814980;hs15:86329774-86329774,hs15:89152327-89152327;hs15:90981137-90981137,hs15:92246749-92246749;hs15:91634249-91634249,hs15:95996492-95996492;hs15:91726190-91726190,hs15:100267686-100267686;hs15:92059060-92059060,hs15:93608950-93608950;hs15:92164886-92164886,hs15:95478041-95478041;hs15:92235968-92235968,hs15:93156035-93156035;hs15:94397058-94397058,hs15:101607021-101607021;hs15:96004500-96004500,hs15:98883741-98883741;hs16:23060241-23060241,hs16:31403655-31403655;hs16:34392074-34392074,hs16:34757694-34757694;hs17:40425539-40425539,hs17:42841837-42841837;hs17:40871405-40871405,hs17:70484793-70484793;hs17:45778542-45778542,hs17:62062756-62062756;hs20:37175080-37175080,hs20:38128173-38128173;hsX:30329289-30329289,hsX:34697281-34697281;hs1:91853156-91853156,hs11:85195254-85195254;hs1:91853160-91853160,hs17:33478115-33478115;hs1:156186608-156186608,hs2:133013266-133013266;hs1:156186653-156186653,hs21:9825502-9825502;hs1:156186658-156186658,hs16:33963027-33963027;hs2:133011919-133011919,hs11:85195004-85195004;hs4:14720073-14720073,hs16:34575253-34575253;hs5:71146950-71146950,hs6:119558561-119558561;hs6:119558561-119558561,hs2:230045479-230045479;hs6:119558562-119558562,hs1:91852808-91852808;hs7:51781390-51781390,hs20:35133757-35133757;hs8:70602305-70602305,hs6:119558571-119558571;hs11:85195239-85195239,hs8:70602526-70602526;hs11:85195240-85195240,hsX:108297333-108297333;hs13:28033989-28033989,hs17:45216213-45216213;hs14:88237836-88237836,hs2:133019404-133019404;hs15:39392920-39392920,hs6:105528299-105528299;hs16:33964168-33964168,hs11:85195001-85195001;hs17:33478359-33478359,hsY:10036228-10036228;hs17:33478374-33478374,hs2:133012240-133012240;hs17:33478374-33478374,hs21:9827584-9827584;hs18:39633392-39633392,hs4:154611152-154611152;hs20:26189003-26189003,hs12:20704363-20704363;hs20:29653973-29653973,hs9:68425923-68425923;hs20:31020888-31020888,hs7:41604686-41604686;hs21:9827563-9827563,hs11:85195002-85195002;hsX:108297333-108297333,hs17:33478118-33478118; ADAMTSL3;ANXA2;BUB1B;CELF6;CHRNA5;CTSH;FURIN;GTF2A2;GLI2;IGF1R;IQGAP1;ISLR;MAPKBP1;MYCN;MYO1E;NAMPT;NEK11;NTRK3;PML;SLC12A6;SMAD3;TCF12;TJP1;ZNF280D;ZNF609;ZNF710 European Molecular Biology Laboratory, Meyerhofstr. 1, 69117 Heidelberg, Germany Genomic rearrangements are thought to occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving massive chromosome rearrangements in a one-step catastrophic event termed chromothripsis. We report the whole-genome sequencing-based analysis of a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome), uncovering massive, complex chromosome rearrangements. Integrating TP53 status with microarray and deep sequencing-based DNA rearrangement data in additional patients reveals a striking association between TP53 mutation and chromothripsis in SHH-MBs. Analysis of additional tumor entities substantiates a link between TP53 mutation and chromothripsis, and indicates a context-specific role for p53 in catastrophic DNA rearrangements. Among these, we observed a strong association between somatic TP53 mutations and chromothripsis in acute myeloid leukemia. These findings connect p53 status and chromothripsis in specific tumor types, providing a genetic basis for understanding particularly aggressive subtypes of cancer. GRCh37/hg19 GSE14437;GSE32462;GSE19101;GSE23452;GSE34323;GSE34258 EGAS00001000085 Yes NA CTDB0116 Research 22265402 Rausch T, Jones DT, Zapatka M, Stutz AM, Zichner T, Weischenfeldt J, Jager N, Remke M, Shih D, Northcott PA, Pfaff E, Tica J, Wang Q, Massimi L, Witt H, Bender S, Pleier S, Cin H, Hawkins C, Beck C, von Deimling A, Hans V, Brors B, Eils R, Scheurlen W, Bl Genome Sequencing of Pediatric Medulloblastoma Links Catastrophic DNA Rearrangements with TP53 Mutations Cell 2012 Jan 2,12 Sonic-Hedgehog medulloblastoma Next Generation Sequencing Homo sapiens LFS-MB4 Illumina HiSeq 2000 chr2:2074250-15913826:-1;chr2:14156532-91794235:-1;chr2:23727492-121124467:-1;chr2:110109209-110251278:-1;chr2:149690550-149790676:-1;chr4:2071045-33527520:-1;chr4:7250202-7366570:-1;chr4:53097786-54003362:-1;chr4:55196757-55277010:-1;chr4:56788702-57032247:-1;chr4:103168108-107714052:-1;chr5:155138565-155188667:-1;chr5:180374717-180432585:-1;chr11:69089751-69139794:-1;chr12:4512391-23390634:-1;chr12:7540228-32371383:-1;chr12:19854988-20369213:-1;chr13:114325864-114426002:-1;chr15:34034045-47295315:-1;chr18:75721852-75772156:-1;chr21:42955390-43005560:-1;chr2:1934384-2074250:1;chr2:15913826-16157942:1;chr2:23554909-23727492:1;chr2:48236089-48566218:1;chr2:56279625-56326244:1;chr2:114704001-115892335:1;chr2:119939305-120031183:1;chr2:121124467-121431476:1;chr2:121432593-123704028:1;chr2:152495756-152743190:1 hs1:91853138-91853138,hs11:85195217-85195217;hs1:91853163-91853163,hs17:33478114-33478114;hs1:156186643-156186643,hs21:9826979-9826979;hs1:156186648-156186648,hs2:133013270-133013270;hs1:156186652-156186652,hs16:33963032-33963032;hs17:33478369-33478369,hs21:9827543-9827543;hs20:29653973-29653973,hs9:68425913-68425913;hs21:9827569-9827569,hs11:85195007-85195007;hs2:1934384-1934384,hs2:120031183-120031183;hs2:16157942-16157942,hs2:48566218-48566218;hs2:23554909-23554909,hs2:48236089-48236089;hs2:56279625-56279625,hs2:123704028-123704028;hs2:56326244-56326244,hs2:152743190-152743190;hs2:85364248-85364248,hs2:88644722-88644722;hs2:114704412-114704412,hs2:152495756-152495756;hs2:115892335-115892335,hs2:121431476-121431476;hs2:119939305-119939305,hs2:121432593-121432593;hs4:38623762-38623762,hs4:41458623-41458623;hs4:56803911-56803911,hs4:56872432-56872432;hs6:157609435-157609435,hs6:157691649-157691649;hs12:2356776-2356776,hs12:2884168-2884168;hs12:2356986-2356986,hs12:2884265-2884265;hs12:3596541-3596541,hs12:21013620-21013620;hs12:3597143-3597143,hs12:21013616-21013616;hs12:4512436-4512436,hs12:19959311-19959311;hs12:5303246-5303246,hs12:22259157-22259157;hs12:11188586-11188586,hs12:29102643-29102643;hs12:19919957-19919957,hs12:20409715-20409715;hs12:19956957-19956957,hs12:20345242-20345242;hs12:19958257-19958257,hs12:23390562-23390562;hs12:20356483-20356483,hs12:23525091-23525091;hs12:20359046-20359046,hs12:23523379-23523379;hs12:20359221-20359221,hs12:23525579-23525579;hs12:20451650-20451650,hs12:22761890-22761890;hs12:22248606-22248606,hs12:22478408-22478408;hs12:22482795-22482795,hs12:23315033-23315033;hs12:23184210-23184210,hs12:23354948-23354948;hs12:23184480-23184480,hs12:23355160-23355160;hs12:31864190-31864190,hs12:32478301-32478301;hs14:26854924-26854924,hs14:30667922-30667922;hs17:41399870-41399870,hs17:41466036-41466036 ALK;FSHR;GIGYF2;GLI2;ITGAV;MSH2;MYCN;NDUFA10;NEB;TMSB10 European Molecular Biology Laboratory, Meyerhofstr. 1, 69117 Heidelberg, Germany Genomic rearrangements are thought to occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving massive chromosome rearrangements in a one-step catastrophic event termed chromothripsis. We report the whole-genome sequencing-based analysis of a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome), uncovering massive, complex chromosome rearrangements. Integrating TP53 status with microarray and deep sequencing-based DNA rearrangement data in additional patients reveals a striking association between TP53 mutation and chromothripsis in SHH-MBs. Analysis of additional tumor entities substantiates a link between TP53 mutation and chromothripsis, and indicates a context-specific role for p53 in catastrophic DNA rearrangements. Among these, we observed a strong association between somatic TP53 mutations and chromothripsis in acute myeloid leukemia. These findings connect p53 status and chromothripsis in specific tumor types, providing a genetic basis for understanding particularly aggressive subtypes of cancer. GRCh37/hg19 GSE14437;GSE32462;GSE19101;GSE23452;GSE34323;GSE34258 EGAS00001000085 Yes ACTR3,NEB CTDB0117 Research 22813740 Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CA, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms Cell Rep 2012 Jun 1,2,15 Congenital abnormality Next Generation Sequencing Homo sapiens Patient1_child AB SOLiD 4 System chr2:173635809-173636102:-1;chr2:178960434-178966476:-1;chr2:145581576-145599659:-1;chr2:128911531-129009714:-1;chr2:178122186-178703789:-1;chr2:143596932-144357565:-1;chr2:124075514-127121524:-1 hs1:243411172-243412608,hs2:146558384-146560016;hs1:243412915-243416373,hs2:124072892-124075186;hs1:247929824-247932508,hs2:145578477-145581427;hs1:247933718-247935923,hs2:173101937-173105197;hs2:127121662-127124079,hs2:178118299-178122101;hs2:128506785-128511173,hs2:128908136-128911334;hs2:128900068-128903965,hs15:27746706-27750284;hs2:128904215-128906395,hs2:129010017-129011058;hs2:128907892-128911115,hs2:145624203-145627873;hs2:143593314-143596595,hs2:144357834-144359901;hs2:145492925-145496715,hs2:173097546-173101766;hs2:145497032-145499296,hs2:178957564-178960096;hs2:145600136-145602568,hs2:145628493-145631256;hs2:146553193-146556447,hs2:173636118-173638697;hs2:148129150-148132374,hs2:174865844-174868962;hs2:148132740-148134862,hs2:174862474-174865044;hs2:173632317-173635702,hs15:27742915-27746403;hs2:178703965-178707145,hs2:178966636-178969213;hs2:128502732-128505748,hs2:128904203-128906409 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. GRCh37/hg19 ERP001035 No NA CTDB0118 Research 22813740 Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CA, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms Cell Rep 2012 Jun 2,8,13 Congenital abnormality Next Generation Sequencing Homo sapiens Patient2_child AB SOLiD 4 System chr8:47918851-47918854:-1;chr13:108222644-108222647:-1;chr2:147801056-147801060:-1;chr8:87670313-87670319:-1;chr13:106187424-106187431:-1;chr13:90127871-90127888:-1;chr8:115818900-115818963:-1;chr2:166014695-166016745:-1;chr13:108216350-108221577:-1;chr13:93370259-93604112:-1;chr2:191897300-194718047:-1;chr2:163141421-166011053:-1;chr2:166014625-166014621:1;chr8:47912515-47912514:1;chr2:148535082-148535082:1;chr13:111879781-111879781:1 hs2:147797698-147801010,hs8:116895627-116898981;hs13:108212580-108216229,hs13:111876035-111879588;hs2:148531325-148534948,hs8:115815125-115818679;hs2:153601572-153605077,hs2:160119416-160123210;hs8:115819103-115822070,hs8:116899526-116902647;hs2:147801050-147804745,hs2:148535258-148538722;hs8:87503991-87507681,hs13:93604139-93607506;hs13:90123892-90127819,hs13:93366610-93369965;hs8:47912597-47915396,hs8:87670525-87674663;hs8:87500983-87503861,hs8:87667009-87669639;hs2:163137520-163141373,hs2:166011421-166014559;hs8:84214080-84217369,hs13:106187688-106191123;hs13:90127935-90131228,hs13:106183766-106187365;hs2:153621846-153625100,hs2:160123294-160127003;hs8:48086057-48089296,hs8:84218139-84224980;hs8:47915790-47918709,hs8:48081547-48084526;hs2:166011148-166014091,hs2:166016838-166020383;hs13:108221815-108222565,hs13:108223657-108226429;hs13:108221938-108222608,hs13:111881628-111883998;hs8:47908213-47912432,hs8:47918838-47921877;hs2:191894679-191897220,hs2:194718106-194721516 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. GRCh37/hg19 ERP001035 No NA CTDB0119 Research 22813740 Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CA, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms Cell Rep 2012 Jun 1,3,7,12 Congenital abnormality Next Generation Sequencing Homo sapiens Patient3_child AB SOLiD 4 System chr3:71078624-71078621:1;chr7:19320228-19320226:1;chr1:97683903-97683903:1;chr7:19114083-19114085:-1;chr1:95146001-95146004:-1;chr12:63505335-63505338:-1;chr1:98219835-98219840:-1;chr7:19003340-19003351:-1;chr7:19512505-19512655:-1;chr3:75208212-76406934:-1;chr7:17140783-18519891:-1;chr7:13962633-15423145:-1;chr7:11404421-13612031:-1 hs1:95143545-95145948,hs1:97683941-97686445;hs1:95145998-95148623,hs3:76407425-76409115;hs1:97681880-97683714,hs7:19111398-19113904;hs1:98218036-98219533,hs7:17138240-17139361;hs1:98219971-98221877,hs7:13960228-13962541;hs3:71076114-71078531,hs3:75205169-75208143;hs3:71078896-71081154,hs7:19000359-19002911;hs7:11401791-11404374,hs7:13612118-13614548;hs7:15423540-15425193,hs12:63503287-63505156;hs7:18519927-18522879,hs7:19317299-19320055;hs7:19003349-19006274,hs7:19114152-19116699;hs7:19510153-19512405,hs12:63505521-63507172;hs7:19320391-19322797,hs7:19512771-19514425 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. GRCh37/hg19 ERP001035 No NA CTDB0120 Research 22813740 Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CA, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms Cell Rep 2012 Jun 2,14 Congenital abnormality Next Generation Sequencing Homo sapiens Patient4_child AB SOLiD 4 System chr14:79136538-79136534:-1;chr2:38345501-38345498:-1 hs2:38343343-38344883,hs14:79136761-79138412;hs2:38345670-38347441,hs14:79133248-79136149;hs14:71206391-71207960,hs14:82090896-82093332;hs14:71204258-71206114,hs14:82088671-82090688 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. GRCh37/hg19 ERP001035 No NA CTDB0121 Research 22813740 Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CA, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms Cell Rep 2012 Jun 6 Congenital abnormality Next Generation Sequencing Homo sapiens Patient5_child AB SOLiD 4 System hs6:49330690-49332603,hs6:53327091-53329211;hs6:49796631-49797278,hs6:84993583-84994052;hs6:50321779-50323964,hs6:54655468-54656553;hs6:53325481-53326844,hs6:84491467-84493206;hs6:50321549-50325789,hs6:54656373-54660096;hs6:51326650-51327743,hs6:54112015-54114279;hs6:52508434-52509910,hs6:54110260-54111080;hs6:50324379-50325713,hs6:54656663-54657903;hs6:84993447-84993553,hs6:96423936-96424166 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. GRCh37/hg19 ERP001035 No NA CTDB0122 Research 22813740 Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CA, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms Cell Rep 2012 Jun 4,8,10,20 Congenital abnormality Next Generation Sequencing Homo sapiens Patient6_child AB SOLiD 4 System chr4:143384762-143384754:1;chr4:122008061-122008054:1;chr4:107840276-107840271:1;chr4:101067666-101067665:1;chr8:128109303-128109303:1;chr10:119944963-119944963:1;chr10:114339361-114339363:-1;chr10:118655641-118655643:-1;chr20:54035355-54035360:-1;chr8:129667371-129667382:-1;chr4:151511931-151511954:-1;chr4:122008107-122008215:-1;chr4:145924134-145929741:-1;chr4:149770244-149791519:-1;chr4:102128766-104640057:-1;chr4:133136227-141993229:-1 hs4:133133185-133135891,hs4:141993252-141996399;hs4:107840319-107842965,hs4:109420612-109423628;hs4:143384774-143387425,hs8:128109571-128112100;hs4:102126233-102128515,hs10:114339489-114342403;hs4:101067986-101071278,hs10:118655643-118658576;hs10:114336536-114339269,hs10:118652430-118655577;hs4:143381854-143384534,hs8:129664308-129667155;hs4:104640064-104642992,hs10:119941564-119944894;hs4:145921501-145924066,hs4:151512450-151515461;hs4:143442035-143443751,hs4:151508728-151511721;hs4:143436471-143439781,hs4:149791618-149794448;hs4:101064731-101067581,hs20:54035382-54037608;hs10:119945272-119947416,hs20:54032823-54035270;hs4:122008261-122011624,hs4:149767569-149770139;hs8:128106730-128109078,hs8:129667834-129669812;hs4:122005620-122007883,hs4:145929750-145933090;hs4:107838052-107839780,hs10:111414267-111416948;hs4:143440657-143442989,hs4:143444329-143447036;hs4:109417384-109420398,hs10:111953671-111956270 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. GRCh37/hg19 ERP001035 No NA CTDB0123 Research 22813740 Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CA, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms Cell Rep 2012 Jun 6,7,9,10,12 Congenital abnormality Next Generation Sequencing Homo sapiens Patient7_mother AB SOLiD 4 System hs7:36718108-36721671,hs12:99787831-99790893;hs9:11739802-11742710,hs9:31460247-31463007;hs9:11758195-11759972,hs12:110263742-110266538;hs9:7104763-7106960,hs12:103464346-103466774;hs9:12236188-12238989,hs9:26965673-26968013;hs9:13236665-13239425,hs12:101859464-101861141;hs6:123750357-123752276,hs9:11743072-11746336;hs6:123765872-123766384,hs12:101856510-101856537;hs9:31433337-31436333,hs9:31463517-31465231;hs9:31471300-31473229,hs12:99435218-99436825;hs6:123748945-123750012,hs6:123768304-123769906;hs10:66227201-66230197,hs12:99785257-99787355;hs9:8118030-8119888,hs10:65848657-65850658;hs7:36714976-36717979,hs12:103467238-103470137;hs9:7107641-7109780,hs9:35723601-35726283;hs9:13334672-13337076,hs9:31473792-31476201;hs9:13240004-13241557,hs9:26962041-26964677;hs9:7116561-7120299,hs9:31436447-31440029;hs9:8121313-8122780,hs9:11760865-11763707;hs9:12233990-12236078,hs12:99431406-99434124;hs9:7113602-7116395,hs12:110267135-110269429;hs9:13337440-13340068,hs12:99636114-99638904;hs10:65844061-65847557,hs10:66230913-66234003 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. GRCh37/hg19 ERP001035 No NA CTDB0124 Research 22813740 Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CA, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms Cell Rep 2012 Jun 7,9,10,12 Congenital abnormality Next Generation Sequencing Homo sapiens Patient7_child AB SOLiD 4 System chr7:36718025-36718027:-1;chr9:11742848-11742851:-1;chr9:31463189-31463192:-1;chr9:31436412-31436439:-1;chr9:7107289-7107387:-1;chr6:123749994-123750143:-1;chr9:13239726-13239970:-1;chr12:99435034-99435026:1;chr9:31473570-31473563:1;chr12:103467187-103467181:1;chr9:12236168-12236165:1;chr9:11760434-11760433:1;chr9:26965302-26965301:1 hs7:36718108-36721671,hs12:99787831-99790893;hs9:11739802-11742710,hs9:31460247-31463007;hs9:11758195-11759972,hs12:110263742-110266538;hs6:123750357-123752276,hs9:11743072-11746336;hs10:66227201-66230197,hs12:99785257-99787355;hs9:8118030-8119888,hs10:65848657-65850658;hs7:36714976-36717979,hs12:103467238-103470137;hs9:7107641-7109780,hs9:35723601-35726283;hs9:13334672-13337076,hs9:31473792-31476201;hs9:13240004-13241557,hs9:26962041-26964677;hs9:7116561-7120299,hs9:31436447-31440029;hs9:8121313-8122780,hs9:11760865-11763707;hs9:12233990-12236078,hs12:99431406-99434124;hs9:7113602-7116395,hs12:110267135-110269429;hs9:13337440-13340068,hs12:99636114-99638904 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. GRCh37/hg19 ERP001035 No NA CTDB0125 Research 22813740 Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CA, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms Cell Rep 2012 Jun 5 Congenital abnormality Next Generation Sequencing Homo sapiens Patient8_child AB SOLiD 4 System chr5:86073427-86073423:1;chr5:85951324-85951326:-1;chr5:87868638-87868756:-1;chr5:85892461-85893557:-1;chr5:158684536-158689801:-1;chr5:87426377-87433416:-1;chr5:85363334-85371155:-1;chr5:158690111-158698437:-1;chr5:86343836-86352568:-1;chr5:86811684-86832176:-1;chr5:158658171-158681667:-1;chr5:158607508-158657977:-1;chr5:85289234-85361626:-1;chr5:85991759-86069335:-1;chr5:158400232-158515794:-1;chr5:87869800-88154277:-1;chr5:87472658-87866129:-1 hs5:85288262-85289063,hs5:87471596-87472480;hs5:85361748-85363159,hs5:85986973-85988074;hs5:85362297-85363176,hs5:85949965-85951002;hs5:85371275-85372561,hs5:158398863-158400207;hs5:85891815-85892371,hs5:87433424-87434332;hs5:85893782-85894176,hs5:87869006-87869529;hs5:85951411-85952184,hs5:158698680-158700075;hs5:85988366-85989838,hs5:87866188-87867502;hs5:86072712-86073373,hs5:87867565-87868374;hs5:86073542-86074750,hs5:158681697-158682944;hs5:86342145-86343603,hs5:86832213-86833137;hs5:86699993-86701408,hs5:88154363-88155823;hs5:87425754-87426279,hs5:158606012-158607009;hs5:87868652-87869713,hs5:158682840-158684494;hs5:86810647-86811269,hs5:158516037-158517066;hs5:85948396-85949213,hs5:86069481-86070538;hs5:85893996-85894198,hs5:85990821-85991347 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. GRCh37/hg19 ERP001035 No NA CTDB0135 Research 23271725 Hirsch D, Kemmerling R, Davis S, Camps J, Meltzer PS, Ried T, Gaiser T Chromothripsis and Focal Copy Number Alterations Determine Poor Outcome in Malignant Melanoma Cancer Res 2013 Mar 5,20 Melanoma Next Generation Sequencing Homo sapiens case14 Illumina HiSeq 2000 Genetics Branch, Center for Cancer Research, National Cancer Institute/NIH, Bethesda, Maryland 20892, USA Genetic changes during tumorigenesis are usually acquired sequentially. However, a recent study showed that in 2% to 3% of all cancers a single catastrophic event, termed chromothripsis, can lead to massive genomic rearrangements confined to one or a few chromosomes. To explore whether the degree of genomic instability and chromothripsis influences prognosis in cancer, we retrospectively applied array-comparative genomic hybridization (aCGH) to 20 malignant melanomas that showed, despite comparable conventional clinical and pathologic parameters, a profoundly different clinical course. We compared 10 patients who died of malignant melanoma 3.7 years (median, range 0.9-7.6 years) after diagnosis with 10 patients who survived malignant melanoma and had a median disease-free survival of 14.8 years (range 12.5-16.7 years; P = 0.00001). We observed a striking association between the degree of chromosomal instability, both numerical and structural, and outcome. Malignant melanomas associated with good prognosis showed only few chromosomal imbalances (mean 1.6 alterations per case), predominantly whole chromosome or chromosome arm gains and losses, whereas malignant melanomas with poor prognosis harbored significantly more chromosomal aberrations (13.9 per case; P = 0.008). Array-based CGH showed that these aberrations were mostly focal events, culminating in two cases in a pattern consistent with the phenomenon of chromothripsis, which was confirmed by paired-end sequencing. This is the first description of chromothripsis in primary malignant melanomas. Our study therefore links focal copy number alterations and chromothripsis with poor outcome in patients with malignant melanomas (P = 0.0002) and provides a genetic approach to predict outcome in malignant melanomas. GRCh37/hg19 Yes NA CTDB0137 Research 22014273 Kloosterman WP, Hoogstraat M, Paling O, Tavakoli-Yaraki M, Renkens I, Vermaat JS, van Roosmalen MJ, van Lieshout S, Nijman IJ, Roessingh W, van 't Slot R, van de Belt J, Guryev V, Koudijs M, Voest E, Cuppen E Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer Genome Biol 2011 Oct 13 Colorectal cancer Next Generation Sequencing Homo sapiens Patient1_primary AB SOLiD 4 System chr2:31723836-31729392:-1;chr2:127550647-150230976:-1;chr3:60289022-60685547:-1;chr4:63174-131357:-1;chr5:18617213-18636314:1;chr5:83668804-83692744:-1;chr7:111063176-111079612:-1;chr10:53184024-53263339:-1;chr13:35646108-82606079:-1;chr13:90427666-90443779:1;chr13:102099102-104364526:1;chr13:104305099-104350436:-1;chr16:6744233-6849498:-1;chrX:133946999-133992828:-1 hs2:92296807-92300718,hs6:61902091-61905238;hs3:30413558-30413724,hs6:58778533-58779075;hs13:23098059-23099917,hs13:78198552-78200182;hs13:35687182-35688469,hs22:36193835-36195196;hs13:36611703-36613693,hs22:19236041-19237588;hs13:59999473-60000660,hs13:105967363-105969749;hs13:68630924-68632686,hs13:77812859-77814463;hs13:68634580-68635862,hs13:90956865-90958345;hs13:71101674-71103995,hs13:90414536-90417027;hs13:90971334-90973021,hs13:92942702-92944416;hs13:101866858-101868336,hs13:102397259-102398969;hs17:20784424-20784934,hs4:33847085-33848798 CCDC144NL;CLTCL1;CTD;DCLK1;EDIL3;FAM122C;FGF14;FHIT;GPC5;IMMP2L;LYPD6;MYCBP2;NALCN;NBEA;PRKG1;RBFOX2;RP11;SCEL;SNORA15;ZNF595;ZNF718 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, 3584 CG, The Netherlands Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear. RESULTS: We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner. CONCLUSIONS: We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis. GRCh37/hg19 GSE32711 ERP000875 Yes SCE,RNA.492;NBEA,RBFOX2;DCLK1,L77569.1;L77569.1,CLTCL1;CLTCL1,SNORA15.3;NALCN,FGF14 CTDB0138 Research 22014273 Kloosterman WP, Hoogstraat M, Paling O, Tavakoli-Yaraki M, Renkens I, Vermaat JS, van Roosmalen MJ, van Lieshout S, Nijman IJ, Roessingh W, van 't Slot R, van de Belt J, Guryev V, Koudijs M, Voest E, Cuppen E Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer Genome Biol 2011 Oct 13 Colorectal cancer Next Generation Sequencing Homo sapiens Patient1_metastasis AB SOLiD 4 System chr2:31723836-31729392:-1;chr2:127550647-150230976:-1;chr4:63174-131357:-1;chr5:18617213-18636314:1;chr13:35646108-82606079:-1;chr13:102099102-104364526:1;chr13:104305099-104350436:-1;chrX:133946999-133992828:-1 hs2:92296807-92300718,hs6:61902091-61905238;hs13:23098059-23099917,hs13:78198552-78200182;hs13:35687182-35688469,hs22:36193835-36195196;hs13:36611703-36613693,hs22:19236041-19237588;hs13:59999473-60000660,hs13:105967363-105969749;hs13:68630924-68632686,hs13:77812859-77814463;hs13:68634580-68635862,hs13:90956865-90958345;hs13:71101674-71103995,hs13:90414536-90417027;hs13:90971334-90973021,hs13:92942702-92944416;hs13:101866858-101868336,hs13:102397259-102398969;hs17:20784424-20784934,hs4:33847085-33848798 CCDC144NL;CLTCL1;DCLK1;FAM122C;FGF14;GPC5;LYPD6;MYCBP2;NALCN;NBEA;RBFOX2;RP11;SCEL;SNORA15;ZNF595;ZNF718 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, 3584 CG, The Netherlands Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear. RESULTS: We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner. CONCLUSIONS: We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis. GRCh37/hg19 GSE32711 ERP000875 Yes SCE,RNA.492;NBEA,RBFOX2;DCLK1,L77569.1;L77569.1,CLTCL1;CLTCL1,SNORA15.3;NALCN,FGF14 CTDB0139 Research 22014273 Kloosterman WP, Hoogstraat M, Paling O, Tavakoli-Yaraki M, Renkens I, Vermaat JS, van Roosmalen MJ, van Lieshout S, Nijman IJ, Roessingh W, van 't Slot R, van de Belt J, Guryev V, Koudijs M, Voest E, Cuppen E Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer Genome Biol 2011 Oct 15,20 Colorectal cancer Next Generation Sequencing Homo sapiens Patient3_primary AB SOLiD 4 System chr1:14814740-14837528:1;chr1:15031539-15273710:-1;chr1:17007460-145382302:1;chr1:42674412-42678368:-1;chr1:56398185-56402750:-1;chr1:86004803-144852992:-1;chr1:184934740-184939911:-1;chr1:194448325-194456448:-1;chr1:217751488-217756636:-1;chr1:242179761-249188200:-1;chr2:1522850-1529807:-1;chr2:206313065-206438788:-1;chr3:60105265-60239906:-1;chr3:60363597-60561868:-1;chr3:60865696-61122653:-1;chr3:82933940-82939170:-1;chr3:145929303-145934420:-1;chr4:36840296-36845327:-1;chr4:49633669-49659602:1;chr4:75323719-75491808:1;chr4:86794119-86799131:-1;chr4:91056889-91200535:-1;chr4:91704626-91736224:-1;chr4:130588752-130593845:-1;chr4:184654896-184659606:-1;chr4:188133117-188138335:-1;chr5:26323330-26327548:-1;chr5:81007149-81011306:-1;chr5:153647671-153796489:-1;chr5:177717867-177723069:-1;chr6:1318456-1322407:-1;chr6:52624253-52710633:-1;chr6:85431705-86318651:-1;chr6:147953818-148039772:1;chr6:149726411-149730778:-1;chr6:162401020-162431070:-1;chr6:162485734-162668565:-1;chr6:162663669-162755553:-1;chr6:162740676-162878837:-1;chr7:40352652-40412225:-1;chr7:64036351-64040567:-1;chr7:110071797-110501925:-1;chr7:142028006-142047406:1;chr7:142454954-142486104:1;chr8:39921544-40184993:-1;chr8:90317285-90386350:-1;chr8:142949641-142954962:-1;chr9:88720666-88725802:-1;chr9:125486301-125515809:-1;chr10:6876069-6880506:-1;chr10:17776474-18026803:-1;chr10:52936928-53050809:-1;chr10:57700014-57705209:-1;chr10:82901884-82906910:-1;chr10:100308414-101176300:1;chr10:126712876-126841247:-1;chr10:127191066-127200309:-1;chr10:134583023-134588259:-1;chr11:18939188-18967485:-1;chr11:66308339-66312407:-1;chr11:98888241-98893290:-1;chr11:134032953-134040158:-1;chr12:11181077-11213498:1;chr12:11250873-11286738:1;chr12:12025612-12030748:-1;chr12:40005354-40010269:-1;chr12:74102385-74107503:-1;chr13:24443874-24449191:-1;chr13:72840317-72850196:-1;chr13:112866635-112871373:-1;chr14:107052457-107133257:1;chr15:27019444-27024926:-1;chr15:56400176-56404784:-1;chr15:71551381-71563088:-1;chr15:75865555-75870469:-1;chr15:91400441-91405105:-1;chr15:91985948-91989513:1;chr16:78637104-78648608:-1;chr16:78820304-78930279:-1;chr16:78937512-79181617:-1;chr17:36540631-36545397:-1;chr17:39387716-39402908:-1;chr18:66202618-66210911:-1;chr19:55202334-55208256:-1;chr20:14571097-14606960:-1;chr20:14776528-14798489:-1;chr20:14786171-15380112:-1;chr20:15191174-15304606:-1;chr20:17101708-17106960:-1;chr20:24901783-24907406:-1;chr20:26288924-26297497:-1;chr20:56391233-56408300:-1;chr20:56428388-56637463:-1;chr20:56613894-57087384:-1;chr21:10732815-10768194:-1;chr21:10759902-10766569:-1;chr21:43701876-43707064:-1;chrX:7328146-7465605:-1;chrX:136079797-136085054:-1 hs1:120600580-120604241,hs1:145220210-145223766;hs1:218631217-218631269,hs6:86025759-86026723;hs1:227777955-227779872,hs1:227831411-227833614;hs2:77396098-77396119,hs3:131669077-131669796;hs2:96517724-96518218,hs7:151926630-151926973;hs2:133024098-133032655,hs11:57222874-57222878;hs2:133026740-133026781,hs11:57222871-57222878;hs2:238517686-238517708,hsX:111772267-111773705;hs3:64980158-64983807,hs3:64986193-64989130;hs4:190190834-190191481,hs9:66454770-66458090;hs6:82992290-82995613,hs7:77506942-77509892;hs6:149225004-149227597,hs7:66030659-66033143;hs6:150084766-150087498,hs6:156637160-156640036;hs6:156634435-156636981,hs7:66461463-66463726;hs7:61783170-61787643,hs7:61803407-61804398;hs8:37418985-37421969,hs8:39900483-39903232;hs8:49949658-49950815,hs13:67503027-67503216;hs8:49955413-49955964,hs13:67503009-67503043;hs10:53515362-53516968,hs3:60538443-60539820;hs10:54712347-54712939,hs4:131717652-131717679;hs11:43653102-43653134,hs17:45212925-45214262;hs11:45848223-45848248,hs11:85195020-85195130;hs12:6108343-6109209,hs22:17161432-17161816;hs12:30402246-30403569,hs12:30499480-30501580;hs14:50896878-50897862,hs7:11557798-11558922;hs15:70210862-70213701,hs20:57469150-57471853;hs15:70216996-70219165,hs20:57131996-57134594;hs15:70226269-70228551,hs15:71505444-71507954;hs15:70233781-70236494,hs20:56438663-56441250;hs15:70529801-70532429,hs15:71634917-71637448;hs15:70796906-70799660,hs20:57147895-57150764;hs15:71202894-71205623,hs20:57069430-57072115;hs15:71322490-71324993,hs15:71325037-71327301;hs15:71750633-71752866,hs20:56183769-56186225;hs16:26346160-26348091,hs16:26349524-26351401;hs16:33982670-33983669,hs4:110818558-110818589;hs19:17140647-17140662,hs2:40777573-40778472;hs19:33444352-33444473,hs20:26211178-26212420;hs19:56558861-56558879,hs8:40312597-40313321;hs20:15083408-15086276,hs21:11181331-11184298;hs20:15084044-15085874,hs22:18886482-18889075;hs20:29637760-29638445,hs4:14424126-14424146;hs21:19938101-19940988,hs21:19940991-19943607;hs21:41398863-41400456,hs21:41403207-41404561;hsX:134755739-134758154,hsX:134801424-134803334;hsY:28578330-28585953,hsY:58968823-58975090 5S_rRNA;ABCD2;ABCG1;AC119751.7;ACTN3;APCDD1L;AREG;AREGB;ARHGAP24;C7orf10;CCDC123;CDC27;CNTN5;COL23A1;CPNE4;CTA;CTB;CTBP2;CTD;DDAH1;DLG2;DSCAM;EIF3FP1;ETV6;FAM129A;FAM190A;FHIT;FOXJ3;GABRB3;GALNT10;GNAS;GOT1;GPATCH2;GS1;GSTA2;GSTA5;HPSE2;HSD17B12;IMMP2L;INPP5A;KRTAP9;LILRP1;LRRC49;LRRTM4;MACROD2;MAP4K5;MIPEP;MLL3;MLLT10P1;MRGPRX1;NCAPD3;NCRNA00227;NLRP5;NOTCH2;NOTCH2NL;OR1L4;OR1L6;PARD3B;PARK2;PCDH9;PCMT1;PDE4DIP;PHTF2;PLSCR4;PRKG1;PRSS1;PTPN9;RFX7;RP1;RP11;RP5;SBDS;SLC8A1;SOCS7;SSBP2;SYNCRIP;TAB2;TAS2R14;TAS2R46;THSD4;THSD7A;TPO;TYW1;UST;VWF_KB;WWOX;ZBP1;ZDHHC24;ZNF678 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, 3584 CG, The Netherlands Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear. RESULTS: We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner. CONCLUSIONS: We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis. GRCh37/hg19 GSE32711 ERP000875 Yes AL109840.2,GNAS;LRRC49,APCDD1L;THSD4,ZBP1;MACROD2,EIF3FP1 CTDB0140 Research 22014273 Kloosterman WP, Hoogstraat M, Paling O, Tavakoli-Yaraki M, Renkens I, Vermaat JS, van Roosmalen MJ, van Lieshout S, Nijman IJ, Roessingh W, van 't Slot R, van de Belt J, Guryev V, Koudijs M, Voest E, Cuppen E Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer Genome Biol 2011 Oct 1 Colorectal cancer Next Generation Sequencing Homo sapiens Patient3_metastasis AB SOLiD 4 System chr1:17007460-145382302:1;chr1:42674412-42678368:-1;chr1:56398185-56402750:-1;chr1:86004803-144852992:-1;chr1:184934740-184939911:-1;chr1:190003041-190552912:-1;chr1:194448325-194456448:-1;chr1:217751488-217756636:-1;chr1:217818705-227823641:1;chr1:226091191-226105416:-1;chr1:237282826-242017394:1;chr1:239542567-242253680:1;chr1:242179761-249188200:-1;chr1:242254059-247564326:1;chr1:242310129-247199201:-1;chr1:246129179-248413010:-1;chr2:1522850-1529807:-1;chr2:187428095-187446066:1;chr2:206112463-206131247:-1;chr3:60105265-60239906:-1;chr3:60363597-60561868:-1;chr3:60865696-61122653:-1;chr3:60966536-60991147:1;chr3:82933940-82939170:-1;chr3:94485781-96367675:-1;chr3:145929303-145934420:-1;chr4:36840296-36845327:-1;chr4:49633669-49659602:1;chr4:75323719-75491808:1;chr4:86794119-86799131:-1;chr4:91056889-91200535:-1;chr4:91171322-91178782:-1;chr4:91704626-91736224:-1;chr4:91855206-91916366:-1;chr4:130588752-130593845:-1;chr4:184654896-184659606:-1;chr4:188133117-188138335:-1;chr5:26323330-26327548:-1;chr5:81007149-81011306:-1;chr5:177717867-177723069:-1;chr6:1318456-1322407:-1;chr6:52624253-52710633:-1;chr6:85431705-86318651:-1;chr6:162401020-162431070:-1;chr6:162485734-162668565:-1;chr6:162663669-162755553:-1;chr6:162740676-162878837:-1;chr6:162750455-163020567:-1;chr7:40352652-40412225:-1;chr7:64036351-64040567:-1;chr7:110985925-111198073:-1;chr7:142028006-142047406:1;chr7:142454954-142486104:1;chr8:39921544-40184993:-1;chr8:90108849-90598688:-1;chr8:90317285-90386350:-1;chr8:142949641-142954962:-1;chr9:88720666-88725802:-1;chr9:125486301-125515809:-1;chr10:6876069-6880506:-1;chr10:17776474-18026803:-1;chr10:52936928-53050809:-1;chr10:53304737-53345051:-1;chr10:53698895-53761643:-1;chr10:53837609-53882685:1;chr10:57700014-57705209:-1;chr10:82901884-82906910:-1;chr10:100308414-101176300:1;chr10:126712876-126841247:-1;chr10:127191066-127200309:-1;chr10:134583023-134588259:-1;chr11:18939188-18967485:-1;chr11:66308339-66312407:-1;chr11:84282887-84450219:-1;chr11:98888241-98893290:-1;chr11:134032953-134040158:-1;chr12:6366670-44077731:-1;chr12:11181077-11213498:1;chr12:11250873-11286738:1;chr12:12025612-12030748:-1;chr12:40005354-40010269:-1;chr12:74102385-74107503:-1;chr13:24443874-24449191:-1;chr13:72840317-72850196:-1;chr13:112866635-112871373:-1;chr14:81528339-81533309:-1;chr14:107052457-107133257:1;chr15:27019444-27024926:-1;chr15:56400176-56404784:-1;chr15:75865555-75870469:-1;chr15:91400441-91405105:-1;chr16:79029865-79114771:-1;chr17:36540631-36545397:-1;chr17:39387716-39402908:-1;chr18:66202618-66210911:-1;chr19:21748981-21754355:-1;chr19:55202334-55208256:-1;chr20:14571097-14606960:-1;chr20:14587575-14763788:-1;chr20:14667618-15219026:-1;chr20:14776528-14798489:-1;chr20:14786171-15380112:-1;chr20:14818777-15034313:-1;chr20:15060067-15185810:-1;chr20:15208210-15273809:-1;chr20:17101708-17106960:-1;chr20:24901783-24907406:-1;chr20:26288924-26297497:-1;chr21:10732815-10768194:-1;chr21:10759902-10766569:-1;chr21:43701876-43707064:-1;chrX:136079797-136085054:-1 hs1:120600580-120604241,hs1:145220210-145223766;hs1:205634139-205636828,hs1:224369508-224372694;hs1:218631217-218631269,hs6:86025759-86026723;hs1:223829777-223832364,hs1:242731112-242733271;hs1:227777955-227779872,hs1:227831411-227833614;hs1:239132977-239133973,hs1:241678276-241678997;hs1:242470743-242472150,hs1:246115529-246117842;hs1:244818903-244821597,hs1:245884999-245887839;hs1:248440300-248443266,hs1:249183012-249185678;hs2:77396098-77396119,hs3:131669077-131669796;hs2:96517724-96518218,hs7:151926630-151926973;hs2:133024098-133032655,hs11:57222874-57222878;hs2:133026740-133026781,hs11:57222871-57222878;hs2:238517686-238517708,hsX:111772267-111773705;hs3:60586434-60587759,hs3:60589085-60590958;hs3:64980158-64983807,hs3:64986193-64989130;hs4:190190834-190191481,hs9:66454770-66458090;hs6:82992290-82995613,hs7:77506942-77509892;hs6:149225004-149227597,hs7:66030659-66033143;hs6:150084766-150087498,hs6:156637160-156640036;hs6:156634435-156636981,hs7:66461463-66463726;hs7:61783170-61787643,hs7:61803407-61804398;hs8:37418985-37421969,hs8:39900483-39903232;hs8:49949658-49950815,hs13:67503027-67503216;hs8:49955413-49955964,hs13:67503009-67503043;hs10:38869743-38874720,hs20:26200325-26201937;hs10:53515362-53516968,hs3:60538443-60539820;hs10:54712347-54712939,hs4:131717652-131717679;hs11:6105038-6105599,hs21:42571840-42571848;hs11:43653102-43653134,hs17:45212925-45214262;hs11:45848223-45848248,hs11:85195020-85195130;hs12:6108343-6109209,hs22:17161432-17161816;hs12:30402246-30403569,hs12:30499480-30501580;hs12:54799942-54802056,hs3:144358420-144360269;hs14:50896878-50897862,hs7:11557798-11558922;hs15:70529801-70532429,hs15:71634917-71637448;hs16:26346160-26348091,hs16:26349524-26351401;hs16:33982670-33983669,hs4:110818558-110818589;hs19:17140647-17140662,hs2:40777573-40778472;hs19:33444352-33444473,hs20:26211178-26212420;hs19:56558861-56558879,hs8:40312597-40313321;hs20:15083408-15086276,hs21:11181331-11184298;hs20:15084044-15085874,hs22:18886482-18889075;hs20:29637760-29638445,hs4:14424126-14424146;hs20:29648025-29648884,hs5:151497083-151497087;hs21:19938101-19940988,hs21:19940991-19943607;hs21:41398863-41400456,hs21:41403207-41404561;hsY:28578330-28585953,hsY:58968823-58975090 5S_rRNA;ABCD2;ABCG1;ACTN3;AREG;AREGB;ARHGAP24;BACE2;C7orf10;CAPN8;CCDC123;CDC27;CNTN5;COL23A1;CPNE4;CTA;CTB;CTBP2;CTD;DDAH1;DEGS1;DLG2;DSCAM;EIF3FP1;ETV6;EXO1;FAM129A;FAM190A;FH;FHIT;FOXJ3;GABRB3;GOT1;GPATCH2;GS1;GSTA2;GSTA5;HPSE2;HSD17B12;IMMP2L;INPP5A;ITGA5;KB;KRTAP9;LEFTY1;LILRP1;LRRTM4;MACROD2;MAP4K5;MIPEP;MLL3;MLLT10P1;MRGPRX1;NCAPD3;NLRP5;NOTCH2;NOTCH2NL;OR1L4;OR1L6;PARD3B;PARK2;PCDH9;PCMT1;PDE4DIP;PHTF2;PLD5;PLSCR4;PPPDE1;PRKG1;PRSS1;PTPN9;PYCR2;RFX7;RP1;RP11;RYR2;SBDS;SLC45A3;SLC8A1;SMYD3;SNORA72;SOCS7;SPATA17;SSBP2;SYNCRIP;TAS2R14;TAS2R46;THSD4;THSD7A;TPO;TSHR;TYW1;U66061;UST;VWF;WWOX;ZDHHC24;ZNF678 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, 3584 CG, The Netherlands Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear. RESULTS: We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner. CONCLUSIONS: We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis. GRCh37/hg19 GSE32711 ERP000875 Yes NOTCH2,NOTCH2NL;NOTCH2NL,RP11-458D21.5;SLC45A3,DEGS1;DEGS1,SNORA72.2;SPATA17,ZNF678;CAPN8,RP11-105I12.1;LEFTY1,PYCR2;RYR2,7SK.259;7SK.259,EXO1 CTDB0141 Research 22014273 Kloosterman WP, Hoogstraat M, Paling O, Tavakoli-Yaraki M, Renkens I, Vermaat JS, van Roosmalen MJ, van Lieshout S, Nijman IJ, Roessingh W, van 't Slot R, van de Belt J, Guryev V, Koudijs M, Voest E, Cuppen E Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer Genome Biol 2011 Oct 3,6,8 Colorectal cancer Next Generation Sequencing Homo sapiens Patient4_primary AB SOLiD 4 System chr1:49802947-49923762:-1;chr2:17406991-17437065:1;chr3:56654445-56988107:-1;chr3:132691793-193107195:-1;chr3:136042870-146982165:1;chr3:148192293-148197662:-1;chr3:174594991-174678318:-1;chr4:53011264-53069377:-1;chr4:107181579-107216856:1;chr4:110618643-110685486:-1;chr5:55466078-55471432:-1;chr5:59214410-59731083:-1;chr6:25006753-97562883:1;chr6:49455879-97565723:-1;chr6:66166717-66625922:-1;chr6:162163387-162185974:-1;chr6:162353175-163192040:-1;chr6:162427029-162443266:-1;chr7:24233931-24239286:-1;chr7:50067894-50190561:-1;chr7:70490878-70500367:-1;chr8:36158315-43649207:-1;chr8:36158830-41285081:1;chr8:36358927-40926150:1;chr8:36440148-39379270:1;chr8:39144393-47113502:1;chr10:65861498-65876909:-1;chr11:62159412-63936774:-1;chr15:20935275-21939883:1;chr16:6248506-6380774:-1;chr16:6586750-6597999:1;chr16:79194156-79272292:-1;chr18:48040416-48170802:-1;chr20:14575911-15363677:-1;chr20:14674638-15391922:-1;chr20:30112996-30342757:1;chrX:6785822-6827028:-1;chrX:7079832-8085559:-1 hs1:163398379-163400456,hs1:203494249-203496422;hs1:163442290-163443321,hs1:203497211-203498241;hs3:96404490-96407077,hs3:96439770-96443240;hs3:96407234-96409302,hs3:96443905-96446423;hs3:116274800-116277310,hs6:62543759-62545039;hs3:116505890-116507162,hs6:72831657-72833123;hs3:119898040-119899910,hs5:53265083-53266766;hs3:121546534-121548528,hs3:140999180-141001121;hs3:121549168-121551138,hs6:8110882-8112019;hs3:133639033-133640150,hs3:150984044-150985508;hs3:136535377-136537190,hs6:100167056-100168340;hs3:136539077-136539760,hs6:72506993-72508522;hs3:143367862-143369638,hs3:162711293-162713354;hs3:146568386-146569737,hs3:167129548-167131401;hs3:146809618-146811762,hs3:192148789-192150935;hs3:153861563-153863907,hs6:7975227-7976587;hs3:161783696-161785511,hs6:100381073-100383094;hs3:165209653-165212672,hs6:24857255-24860048;hs3:165260710-165263099,hs5:53505897-53508673;hs3:165773176-165775886,hs6:25994741-25997121;hs3:166524585-166527014,hs6:48537273-48539587;hs3:167515728-167518568,hs3:192530891-192533361;hs3:190616878-190619384,hs3:191135633-191137944;hs3:191542736-191545061,hs6:48108422-48110492;hs3:191611575-191612274,hs6:97835272-97836598;hs3:192155007-192156944,hs6:96782363-96783869;hs3:192534485-192536549,hs6:9333886-9336407;hs5:42882085-42883238,hs6:8108078-8109181;hs5:43672276-43674850,hs9:111708726-111710521;hs6:30222990-30225620,hs6:62895896-62897791;hs6:49361807-49364428,hs6:97836756-97838746;hs6:98390444-98392418,hs9:111427832-111430237;hs6:170909787-170911773,hs13:115106076-115109812;hs8:34330731-34333534,hs8:36782127-36785088;hs8:34331178-34333393,hs8:36511593-36513948;hs8:36867812-36870275,hs8:37789646-37791368;hs8:36912234-36914139,hs8:47119771-47121748;hs8:37473964-37476378,hs8:39390152-39392532;hs11:28546711-28548304,hs6:156302660-156304279;hs11:57028414-57030219,hs11:62164189-62166303;hs11:57390222-57393033,hs21:16464636-16466584;hs12:6661831-6663841,hs12:11479949-11482679;hs12:22241562-22243488,hs12:23901258-23903320;hs12:23923589-23925428,hs6:7620692-7623368;hs12:25696603-25699039,hs3:190805806-190808367;hs12:26078257-26080398,hs3:161917893-161919793;hs14:107026331-107028138,hs17:50697866-50699916;hs15:74653331-74655310,hs17:77772433-77773698;hs20:5709889-5710952,hs20:5711237-5712971;hs20:42881540-42883261,hs20:44091225-44093313;hs20:43974701-43976700,hs20:45117980-45120314 ACPL2;ADAM32;ADAM3A;AGBL4;ANKRD55;ARHGEF26;ARHGEF3;ARL15;ASRGL1;C3orf59;C3orf63;C7orf72;C9orf6;CASP6;CBX1P5;CBX8;CCDC66;CENPQ;CFI;CTD;CTNNAL1;CYP11A1;EAF2;EYSPACRG;FAM65B;FGF12;GDAP1L1;GOT1L1;GPR156;HLA-L;HM13;IFFO1;IFLTD1;IQCB1;KCNU1;KHDRBS2;KLHL32;LSAMP;MACROD1;MACROD2;MAPK4;MCHR2;MED12L;MUTED;NAALADL2;NCRNA00227;NNT;NOP2;P2RY14;PARK2;PCCB;PDE4D;RIMS1;RP1;RP11;SDC4;SEPP1;SERPINI1;SLC9A9;SNORD65.4;SOX5;TBCK;TMEM22;TPX2;WWOX;ZNF840;ZPBP Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, 3584 CG, The Netherlands Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear. RESULTS: We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner. CONCLUSIONS: We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis. GRCh37/hg19 GSE32711 ERP000875 Yes CCDC66,C3orf63;C3orf63,ARHGEF3;ARHGEF3,RP11-51O17.1;LSAMP,RP11-63L4.1;RP11-63L4.1,KHDRBS2;LSAMP,RIMS1;GPR156,ARL15;ARL15,AC034246.1;IQCB1,ACPL2;ACPL2,RP11-438D8.2;IQCB1,EAF2;MED12L,P2RY14;P2RY14,RP11-600P18.4;PCCB,RP11-649A16.1;RP11-649A16.1,FGF12;ARHGEF26,MUTED;RP11-85M11.2,FAM65B;RP11-85M11.2,ARL15;ARL15,AC034246.1;SERPINI1,C3orf59;NAALADL2,RP11-432A8.2;RP11-432A8.2,NAALADL2;NAALADL2,RP11-432A8.2;AL662795.3,AL662795.4;AL662795.4,HLA-L;HLA-L,KHDRBS2;CENPQ,KLHL32;RP11-962G15.1,RP1-155O2.1;RP1-155O2.1,ADAM3A;ADAM3A,AC123767.2 CTDB0142 Research 22014273 Kloosterman WP, Hoogstraat M, Paling O, Tavakoli-Yaraki M, Renkens I, Vermaat JS, van Roosmalen MJ, van Lieshout S, Nijman IJ, Roessingh W, van 't Slot R, van de Belt J, Guryev V, Koudijs M, Voest E, Cuppen E Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer Genome Biol 2011 Oct 8,17,21 Colorectal cancer Next Generation Sequencing Homo sapiens Patient4_metastasis AB SOLiD 4 System chr1:162534083-162562304:-1;chr2:17406991-17437065:1;chr5:55466078-55471432:-1;chr6:87330569-114998264:-1;chr6:162353175-163192040:-1;chr6:162427029-162443266:-1;chr7:24233931-24239286:-1;chr8:39144393-47113502:1;chr9:96569412-100368804:-1;chr11:62159412-63936774:-1;chr14:64687236-64720590:1;chr15:20935275-21939883:1;chr16:6248506-6380774:-1;chr16:6586750-6597999:1;chr16:79194156-79272292:-1;chr17:32113189-60139461:-1;chr17:40814703-70143738:1;chr17:64277098-72940896:1;chr18:48040416-48170802:-1;chr18:76525020-76540965:-1;chrX:6785822-6827028:-1 hs1:163398379-163400456,hs1:203494249-203496422;hs1:163442290-163443321,hs1:203497211-203498241;hs1:208378873-208380330,hs18:29271081-29273046;hs3:96404490-96407077,hs3:96439770-96443240;hs3:96407234-96409302,hs3:96443905-96446423;hs3:136539077-136539760,hs6:72506993-72508522;hs3:165773176-165775886,hs6:25994741-25997121;hs3:191611575-191612274,hs6:97835272-97836598;hs6:170909787-170911773,hs13:115106076-115109812;hs8:34331178-34333393,hs8:36511593-36513948;hs8:36867812-36870275,hs8:37789646-37791368;hs15:74653331-74655310,hs17:77772433-77773698;hs17:32112860-32113771,hs21:36078807-36080162;hs17:34387513-34388512,hs17:69836276-69837799;hs17:36271457-36274015,hs17:69794557-69797324;hs17:60138913-60139352,hs21:47004072-47004879;hs17:61528927-61531431,hs21:44019447-44021284;hs17:69672120-69672487,hs21:47004076-47004243;hs17:69672131-69672690,hs21:36077556-36079034;hs20:5709889-5710952,hs20:5711237-5712971;hs20:42881540-42883261,hs20:44091225-44093313 ACCN1;ADAM32;ANKRD55;AP001626.1;ASRGL1;CBX8;CLIC6;CTD;CYP11A1;ESR2;GDAP1L1;GOT1L1;MACROD1;MAPK4;MED13;OTOP3;PACRG;PARK2;PLEKHH3;PLXNA2;RP11;SYNE2;TMEM22;TMOD1;TSTD2;TUBG2;UAP1;WWOX Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, 3584 CG, The Netherlands Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear. RESULTS: We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner. CONCLUSIONS: We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis. GRCh37/hg19 GSE32711 ERP000875 Yes ACCN1,CLIC6;ACCN1,MED13;TUBG2,PLEKHH3;PLEKHH3,AC005152.2 CTDB0160 Research 24509483 McEvoy J, Nagahawatte P, Finkelstein D, Richards-Yutz J, Valentine M, Ma J, Mullighan C, Song G, Chen X, Wilson M, Brennan R, Pounds S, Becksfort J, Huether R, Lu C, Fulton RS, Fulton LL, Hong X, Dooling DJ, Ochoa K, Mardis ER, Wilson RK, Easton J, Zhang RB1 gene inactivation by chromothripsis in human retinoblastoma. Oncotarget 2014 Jan 13 Retinoblastoma Next Generation Sequencing Homo sapiens SJRB031 Illumina sequencing CAB39L;DACH1;EBPL;ENOX1;KLHL1;LMO7;RB1 Departments of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA Retinoblastoma is a rare childhood cancer of the developing retina. Most retinoblastomas initiate with biallelic inactivation of the RB1 gene through diverse mechanisms including point mutations, nucleotide insertions, deletions, loss of heterozygosity and promoter hypermethylation. Recently, a novel mechanism of retinoblastoma initiation was proposed. Gallie and colleagues discovered that a small proportion of retinoblastomas lack RB1 mutations and had MYCN amplification. In this study, we identified recurrent chromosomal, regional and focal genomic lesions in 94 primary retinoblastomas with their matched normal DNA using SNP 6.0 chips. We also analyzed the RB1 gene mutations and compared the mechanism of RB1 inactivation to the recurrent copy number variations in the retinoblastoma genome. In addition to the previously described focal amplification of MYCN and deletions in RB1 and BCOR, we also identified recurrent focal amplification of OTX2, a transcription factor required for retinal photoreceptor development. We identified 10 retinoblastomas in our cohort that lacked RB1 point mutations or indels. We performed whole genome sequencing on those 10 tumors and their corresponding germline DNA. In one of the tumors, the RB1 gene was unaltered, the MYCN gene was amplified and RB1 protein was expressed in the nuclei of the tumor cells. In addition, several tumors had complex patterns of structural variations and we identified 3 tumors with chromothripsis at the RB1 locus. This is the first report of chromothripsis as a mechanism for RB1 gene inactivation in cancer. Yes NA CTDB0161 Research 24509483 McEvoy J, Nagahawatte P, Finkelstein D, Richards-Yutz J, Valentine M, Ma J, Mullighan C, Song G, Chen X, Wilson M, Brennan R, Pounds S, Becksfort J, Huether R, Lu C, Fulton RS, Fulton LL, Hong X, Dooling DJ, Ochoa K, Mardis ER, Wilson RK, Easton J, Zhang RB1 gene inactivation by chromothripsis in human retinoblastoma. Oncotarget 2014 Jan 13 Retinoblastoma Next Generation Sequencing Homo sapiens SJRB039 Illumina sequencing CAB39L;DIAPH3;ENOX1;GPC5;KLF12;PIBF1;RB1;SLC35F4;TBC1D4;TDRD3 Departments of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA Retinoblastoma is a rare childhood cancer of the developing retina. Most retinoblastomas initiate with biallelic inactivation of the RB1 gene through diverse mechanisms including point mutations, nucleotide insertions, deletions, loss of heterozygosity and promoter hypermethylation. Recently, a novel mechanism of retinoblastoma initiation was proposed. Gallie and colleagues discovered that a small proportion of retinoblastomas lack RB1 mutations and had MYCN amplification. In this study, we identified recurrent chromosomal, regional and focal genomic lesions in 94 primary retinoblastomas with their matched normal DNA using SNP 6.0 chips. We also analyzed the RB1 gene mutations and compared the mechanism of RB1 inactivation to the recurrent copy number variations in the retinoblastoma genome. In addition to the previously described focal amplification of MYCN and deletions in RB1 and BCOR, we also identified recurrent focal amplification of OTX2, a transcription factor required for retinal photoreceptor development. We identified 10 retinoblastomas in our cohort that lacked RB1 point mutations or indels. We performed whole genome sequencing on those 10 tumors and their corresponding germline DNA. In one of the tumors, the RB1 gene was unaltered, the MYCN gene was amplified and RB1 protein was expressed in the nuclei of the tumor cells. In addition, several tumors had complex patterns of structural variations and we identified 3 tumors with chromothripsis at the RB1 locus. This is the first report of chromothripsis as a mechanism for RB1 gene inactivation in cancer. Yes NA CTDB0162 Research 24509483 McEvoy J, Nagahawatte P, Finkelstein D, Richards-Yutz J, Valentine M, Ma J, Mullighan C, Song G, Chen X, Wilson M, Brennan R, Pounds S, Becksfort J, Huether R, Lu C, Fulton RS, Fulton LL, Hong X, Dooling DJ, Ochoa K, Mardis ER, Wilson RK, Easton J, Zhang RB1 gene inactivation by chromothripsis in human retinoblastoma. Oncotarget 2014 Jan 13 Retinoblastoma Next Generation Sequencing Homo sapiens SJRB051 Illumina sequencing Departments of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA Retinoblastoma is a rare childhood cancer of the developing retina. Most retinoblastomas initiate with biallelic inactivation of the RB1 gene through diverse mechanisms including point mutations, nucleotide insertions, deletions, loss of heterozygosity and promoter hypermethylation. Recently, a novel mechanism of retinoblastoma initiation was proposed. Gallie and colleagues discovered that a small proportion of retinoblastomas lack RB1 mutations and had MYCN amplification. In this study, we identified recurrent chromosomal, regional and focal genomic lesions in 94 primary retinoblastomas with their matched normal DNA using SNP 6.0 chips. We also analyzed the RB1 gene mutations and compared the mechanism of RB1 inactivation to the recurrent copy number variations in the retinoblastoma genome. In addition to the previously described focal amplification of MYCN and deletions in RB1 and BCOR, we also identified recurrent focal amplification of OTX2, a transcription factor required for retinal photoreceptor development. We identified 10 retinoblastomas in our cohort that lacked RB1 point mutations or indels. We performed whole genome sequencing on those 10 tumors and their corresponding germline DNA. In one of the tumors, the RB1 gene was unaltered, the MYCN gene was amplified and RB1 protein was expressed in the nuclei of the tumor cells. In addition, several tumors had complex patterns of structural variations and we identified 3 tumors with chromothripsis at the RB1 locus. This is the first report of chromothripsis as a mechanism for RB1 gene inactivation in cancer. Yes NA CTDB0166 Research 25043231 Macera MJ, Sobrino A, Levy B, Jobanputra V, Aggarwal V, Mills A, Esteves C, Hanscom C, Pereira S, Pillalamarri V, Ordulu Z, Morton CC, Talkowski M, Warburton D Prenatal diagnosis of chromothripsis, with nine breaks characterized by karyotyping, FISH, microarray and whole-genome sequencing. Prenat Diagn 2015 Mar 3,5,7,9,18 Congenital abnormality Next Generation Sequencing Homo sapiens DGAP259 Next Generation Sequencing CNTN6;TBC1D5;CNTNAP2;PTPRD;L3MBTL4;LOC1001304840;WDR7 New York Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA Detection of de novo complex chromosomal rearrangements (CCRs) in prenatal testing is extremely rare. GRCh37/hg19 No NA CTDB0168 Research 24553141 Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 2014 Feb 11,X Ependymoma Next Generation Sequencing Homo sapiens ST1 Illumina HighSeq chr1:104832967-104833096:1;chr1:171879830-171880254:-1;chr2:143354888-143355200:-1;chr3:39982712-39982775:-1;chr3:122974354-129582837:-1;chr4:24922134-24922461:-1;chr4:24922462-24922952:-1;chr5:2946120-2946160:-1;chr5:94989965-94990056:-1;chr5:174154229-174562491:-1;chr7:10001-27329444:-1;chr7:27329445-27329874:-1;chr7:27329875-31315100:-1;chr7:31319001-54630074:-1;chr8:37577274-37577350:1;chr9:10001-21536600:-1;chr9:21541901-25995100:-1;chr10:74825643-74825652:-1;chr10:83584958-129868251:-1;chr11:57650053-57652830:-1;chr11:57929507-58195900:-1;chr11:59573214-59575583:-1;chr11:62710036-62710800:-1;chr11:63532366-63532663:-1;chr12:37856901-52825995:-1;chr13:41260227-41260323:-1;chr14:59262405-80667437:-1;chr15:87647553-87647681:1;chr16:60001-1838600:-1;chr17:1-5559444:-1;chr17:18777000-18778417:-1;chr17:18778418-22262900:-1;chrX:2699501-3252000:-1;chrX:3563855-3565369:-1;chrX:5076171-5076758:-1;chrX:6450401-6572700:-1;chrX:7026014-7031348:-1;chrX:7204201-7878680:-1;chrX:10257802-10258307:-1;chrX:10288225-10289018:-1;chrX:12684501-13800900:-1;chrX:14059854-14062493:-1;chrX:14501208-14573201:-1;chrX:15960869-17037846:-1;chrX:17783726-18674577:-1;chrX:19819162-20337772:-1;chrX:20362177-20362595:-1;chrX:21950811-22331591:-1;chrX:24816223-24817518:-1;chrX:25633328-25639598:-1;chrX:25707801-25710473:-1;chrX:25906500-27333286:-1;chrX:27682922-27683435:-1;chrX:28116542-28120495:-1;chrX:28695436-28698997:-1;chrX:28819370-29255916:-1;chrX:29556701-30600154:-1;chrX:32120627-33632538:-1;chrX:34551211-34551503:-1;chrX:36690510-36690680:-1;chrX:39852159-40046659:-1;chrX:40401201-41130390:-1;chrX:41193741-42775228:-1;chrX:43674229-43912400:-1;chrX:44041607-44044302:-1;chrX:44425001-44520906:-1;chrX:44752480-45003198:-1;chrX:45749246-45750155:-1;chrX:47116411-47118418:-1;chrX:47470775-47471747:-1;chrX:47535706-47538629:-1;chrX:48210401-49572700:-1;chrX:53039011-54217000:-1;chrX:55868160-57305500:-1;chrX:57642521-58435105:-1;chrX:63068540-63070815:-1;chrX:63389676-63402346:-1;chrX:65036456-65037833:-1;chrX:65188944-69976309:-1;chrX:71429013-73370020:-1;chrX:74422088-76999395:-1;chrX:77585648-77591230:-1;chrX:78152682-79735737:-1;chrX:80083235-82669137:-1;chrX:82975826-84052962:-1;chrX:85342676-85343735:-1;chrX:85868035-88322300:-1;chrX:88429173-91810300:-1;chrX:94804301-95927757:-1;chrX:96386377-96387146:-1;chrX:97899343-100042500:-1;chrX:101187368-101188600:-1;chrX:104558838-106399000:-1;chrX:108488501-108490798:-1;chrX:108810040-109857300:-1;chrX:110944279-114275312:-1;chrX:114352071-114804672:-1;chrX:114849860-116062600:-1;chrX:116126307-116128265:-1;chrX:119490946-119503789:-1;chrX:122690172-122694452:-1;chrX:127472563-127473080:1;chrX:127757855-127764441:-1;chrX:130153401-130350301:-1;chrX:130868210-130878000:-1;chrX:131129532-131131850:-1;chrX:132876306-133869756:-1;chrX:135206545-141207540:-1;chrX:141509774-146046706:-1;chrX:146230484-146231119:-1;chrX:149296142-151686899:-1;chrY:2649501-59033300:-1 hs4:24922462-24922462,hs4:24922953-24922953;hs13:41260227-41260227,hs13:41260324-41260324;hsX:146046707-146046707,hsX:30600153-30600153;hsX:47471748-47471748,hsX:24817519-24817519;hs1:104833097-104833097,hs1:104832967-104832967;hsX:27682922-27682922,hsX:63070816-63070816;hsX:63402347-63402347,hsX:18674578-18674578;hs19:47286731-47286731,hs19:47631722-47631722;hs10:74825653-74825653,hs1:11956719-11956719;hsX:104227959-104227959,hsX:110944279-110944279;hs4:146807124-146807124,hs3:36964923-36964923;hs4:24922134-24922134,hs4:24922243-24922243;hsX:40046660-40046660,hsX:20362596-20362596;hs7:27329875-27329875,hs7:27329445-27329445;hsX:65037834-65037834,hsX:47118419-47118419;hsX:44041607-44041607,hsX:55868160-55868160;hs3:122974354-122974354,hs3:129582838-129582838;hsX:57642521-57642521,hsX:146231120-146231120;hsX:44520907-44520907,hsX:101188609-101188609;hs11:59493240-59493240,hsX:108488358-108488358;hs7:54630075-54630075,hs17:5559445-5559445;hs4:146807124-146807124,hs3:36964923-36964923;hs3:36964923-36964923,hs4:146807124-146807124;hs11:20216746-20216746,hs11:20216379-20216379;hsX:127757855-127757855,hsX:3565370-3565370;hsX:132876306-132876306,hsX:41130391-41130391;hsX:89810377-89810377,hsX:101187368-101187368;hs10:37610550-37610550,hs10:37610590-37610590;hsX:7026014-7026014,hsX:36690510-36690510;hsX:63389676-63389676,hsX:48212619-48212619;hsX:36275735-36275735,hsX:107385724-107385724;hsX:24816223-24816223,hsX:28819370-28819370;hs1:171879830-171879830,hs1:171880255-171880255;hsX:65188944-65188944,hsX:85342676-85342676;hsX:14573202-14573202,hsX:5076759-5076759;hsX:126559481-126559481,hsX:58435106-58435106;hsX:480398-480398,hsX:131131836-131131836;hsX:65036456-65036456,hsX:10289019-10289019;hsX:19819162-19819162,hsX:28116542-28116542;hs11:20216380-20216380,hs11:20216732-20216732;hsX:104227959-104227959,hsX:110944279-110944279;hsX:96386377-96386377,hsX:33632539-33632539;hsX:85868035-85868035,hsX:36690681-36690681;hsX:24577792-24577792,hsX:71429013-71429013;hs4:2618024-2618024,hs4:8990111-8990111;hsX:82669138-82669138,hsX:57305567-57305567;hs11:57650053-57650053,hsX:1939779-1939779;hsX:24577792-24577792,hsX:71429013-71429013;hsX:28695436-28695436,hsX:78152682-78152682;hs1:11956717-11956717,hs10:74825643-74825643;hsX:149296142-149296142,hsX:122694453-122694453;hs11:56037616-56037616,hs11:56975933-56975933;hs11:62710833-62710833,hs11:59575584-59575584;hsX:480398-480398,hsX:131131884-131131884;hs11:63803018-63803018,hsX:7031349-7031349;hsX:47116411-47116411,hsX:127764442-127764442;hsX:53039011-53039011,hsX:128246576-128246576;hsX:130878065-130878065,hsX:27333287-27333287;hsX:39852159-39852159,hsX:6572723-6572723;hs11:59573214-59573214,hs11:62092169-62092169;hs17:18777000-18777000,hs17:18778418-18778418;hs2:82825123-82825123,hs12:109544683-109544683;hsX:130868210-130868210,hsX:146230484-146230484;hsX:116126307-116126307,hsX:119490946-119490946;hsX:141207541-141207541,hsX:29255917-29255917;hs11:57166146-57166146,hs11:63532366-63532366;hsX:25633328-25633328,hsX:73370021-73370021;hsX:4396761-4396761,hsX:116128266-116128266;hsX:151686900-151686900,hsX:3731434-3731434;hsX:43674229-43674229,hsX:141509774-141509774;hs15:87647682-87647682,hs15:87647553-87647553;hs11:57929507-57929507,hsX:122690172-122690172;hsX:104228306-104228306,hsX:45750156-45750156;hsX:3477486-3477486,hsX:108490799-108490799;hsX:44424889-44424889,hsX:48210160-48210160;hsX:45749246-45749246,hsX:69976310-69976310;hs4:8990108-8990108,hs4:2618044-2618044;hs5:174154229-174154229,hs5:174562492-174562492;hsX:47470775-47470775,hsX:45003199-45003199;hsX:3563855-3563855,hsX:85343736-85343736;hsX:10257802-10257802,hsX:127473081-127473081;hsX:36275735-36275735,hsX:107385724-107385724;hsX:20362177-20362177,hsX:22331592-22331592;hsX:114849860-114849860,hsX:10258308-10258308;hsX:74214442-74214442,hsX:47538630-47538630;hsX:47535706-47535706,hsX:25639599-25639599;hs10:83584958-83584958,hsX:133869757-133869757;hs6:134154525-134154525,hs6:134154654-134154654;hsX:1938642-1938642,hs11:62504341-62504341;hs12:125075171-125075171,hs7:108535540-108535540;hs3:122974354-122974354,hs3:129582838-129582838;hsX:17783726-17783726,hsX:77200372-77200372;hs7:108535523-108535523,hs12:125075213-125075213;hsX:25906500-25906500,hsX:114804673-114804673;hsX:24816223-24816223,hsX:28819370-28819370;hs11:62710036-62710036,hs11:64585212-64585212;hsX:131129532-131129532,hsX:28698998-28698998;hsX:5076171-5076171,hsX:108065139-108065139;hs2:143354888-143354888,hs2:143355519-143355519;hsX:119503790-119503790,hsX:7878681-7878681;hsX:21950811-21950811,hsX:97899343-97899343;hsX:34551504-34551504,hsX:20337773-20337773;hsX:14059854-14059854,hsX:14501208-14501208;hs5:94989965-94989965,hs5:94990057-94990057;hsX:104558838-104558838,hsX:95927758-95927758;hsX:34551211-34551211,hsX:41193741-41193741;hs10:24505424-24505424,hs10:24507786-24507786;hsX:115633772-115633772,hsX:126561457-126561457;hsX:88429173-88429173,hsX:91823311-91823311;hsX:127472563-127472563,hsX:6729931-6729931;hsX:32120627-32120627,hsX:79735738-79735738;hsX:15960869-15960869,hsX:76999396-76999396;hsX:74422088-74422088,hsX:130350302-130350302;hs11:65430153-65430153,hs11:63532664-63532664;hsX:63068535-63068535,hsX:14062494-14062494;hsX:44752477-44752477,hsX:44044303-44044303;hsX:114352071-114352071,hsX:27683436-27683436;hsX:10288225-10288225,hsX:84052963-84052963;hsX:42775229-42775229,hsX:17037847-17037847;hsX:90134362-90134362,hsX:135206545-135206545;hsX:108810040-108810040,hs11:57652831-57652831;hsX:25707750-25707750,hsX:74214889-74214889;hsX:28813516-28813516,hsX:25710474-25710474;hs7:54630075-54630075,hs17:5559445-5559445;hsX:44752477-44752477,hsX:44044303-44044303;hs5:172811557-172811557,hs5:172811639-172811639;hsX:114275313-114275313,hsX:28120496-28120496;hs14:59262405-59262405,hs14:80667438-80667438;hs3:39982712-39982712,hs3:39982776-39982776;hs3:36964923-36964923,hs4:146807124-146807124 SYN1_POLA1;RS1;SLC1A5;P4HA1;ALG13;ZNF827;EFHC2;SEC22A;LOC285878;TRANK1;PRKX;GPC3;HDHD1;SSX3;ATG4A;IL1RAPL1;GLRA2;SH3KBP1;IL1RAPL2;DIAPH2;DACH2;ERCC6L;PIN4;MRPL16;HDHD1_MACROD1;LOC286467;STX3;PRPSAP2;UNG;C11orf95;FTX;MAOB;OR9Q1;TEX11;MSX2;SYN1;CXorf30;PLS3;TTC9C;TMCC1;ATP7A;POLA1;PNPLA4_ATP1B4;RFESD_RFESD;DDX3X;KIAA1217;PCDH11X;DMD;ATRX;C11orf95_RELA;LRCH2;REPS2;VSTM2A;KDM6A;DIO2 St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA Members of the nuclear factor-kappaB (NF-kappaB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-kappaB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-kappaB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-kappaB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-kappaB target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma. GRCh37/hg19 EGAS00001000254 Yes C1orf95,RELA;HDHD1,MACROD1;PRG2,C11orf95 CTDB0169 Research 24553141 Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 2014 Feb 1,11 Ependymoma Next Generation Sequencing Homo sapiens ST2 Illumina HighSeq chr1:10101-23950200:-1;chr1:24078468-24080192:-1;chr2:10001-44700:1;chr2:128536801-128537500:-1;chr9:10001-141108100:-1;chr11:133701-55365400:-1;chr11:55459601-55784390:-1;chr11:56496718-56497900:1;chr11:56498057-56498168:1;chr11:56498169-56498545:1;chr11:56498546-56498608:1;chr11:56663001-56677510:-1;chr11:57352433-57353960:-1;chr11:57533945-57537111:-1;chr11:59910169-59912939:-1;chr11:60691595-60693442:-1;chr11:60840946-61159547:-1;chr11:61316664-61318506:-1;chr11:61742963-61745364:-1;chr11:62310777-62312488:-1;chr11:62462371-62464600:-1;chr11:63532010-64841368:1;chr11:64841369-64842810:-1;chr11:64842811-65429800:1;chr11:65429801-65431371:-1;chr11:65431372-65962744:1;chr11:65962745-65964931:-1;chr11:65964932-66178051:1;chr11:66178052-66505173:-1;chr11:66505174-76257798:1;chr11:76257799-77208636:-1;chr11:77874774-77877400:-1;chr11:78148643-78151579:-1;chr11:79130183-79133520:-1;chr11:79133521-80288992:1;chr11:80288993-80290733:-1;chr11:82249727-82253741:-1;chr11:83112371-83115905:-1;chr11:83115906-84613700:1;chr11:84613701-85617848:-1;chr11:85617849-86132389:1;chr11:88973847-88973900:1;chr11:88974001-88974300:1;chr11:88974365-88974484:1;chr11:88974485-88975242:-1;chr11:90813909-90819550:-1;chr11:90819551-92388918:1;chr11:92388919-92390137:-1;chr11:92390138-93274768:1;chr11:93274769-93275375:-1;chr11:93275376-118523766:1;chr11:118523767-133075931:-1;chr11:133459430-133461682:-1;chr11:134929801-134946400:1 hs11:64983067-64983067,hs11:64983501-64983501;hs3:34432532-34432532,hs3:34433003-34433003;hs11:57352433-57352433,hs11:83112371-83112371;hs11:57353961-57353961,hs11:56898805-56898805;hs6:109203696-109203696,hs6:109202055-109202055;hs13:56880933-56880933,hs13:56881767-56881767;hs11:56498169-56498169,hs11:88973888-88973888;hs11:56498609-56498609,hs11:86132705-86132705;hs11:86133004-86133004,hs11:88973932-88973932;hs1:24078468-24078468,hs11:82249727-82249727;hs11:93274769-93274769,hs11:66505174-66505174;hs11:65962745-65962745,hs11:79133521-79133521;hs11:77874774-77874774,hs11:57537112-57537112;hs11:92390138-92390138,hs11:65964932-65964932;hs11:56498022-56498022,hs11:88974396-88974396;hs11:88671613-88671613,hs11:62464596-62464596;hs11:56498609-56498609,hs11:86132705-86132705;hs11:56498169-56498169,hs11:88973888-88973888;hs7:20016970-20016970,hs7:20018602-20018602;hs11:92390138-92390138,hs11:65964932-65964932;hs11:56498022-56498022,hs11:88974396-88974396;hs11:60691595-60691595,hs11:57467033-57467033;hs11:86133004-86133004,hs11:88973932-88973932;hs11:88974331-88974331,hs11:85617849-85617849;hs11:56498169-56498169,hs11:88973888-88973888;hs11:62462371-62462371,hs1:24080193-24080193;hs11:76257799-76257799,hs11:56496718-56496718;hs11:77877366-77877366,hs11:62312489-62312489;hs11:78148643-78148643,hs11:88974372-88974372;hs17:42676519-42676519,hs2:58227721-58227721;hs11:56498169-56498169,hs11:88973888-88973888;hs11:133075932-133075932,hs11:61318507-61318507;hs21:25629382-25629382,hs21:25633408-25633408;hs11:90819551-90819551,hs11:65431372-65431372;hs11:86133004-86133004,hs11:88973932-88973932;hs11:61742963-61742963,hs11:55784391-55784391;hs11:88974365-88974365,hs11:88973839-88973839;hs11:56498169-56498169,hs11:88973888-88973888;hs11:56498057-56498057,hs11:60840946-60840946;hs11:88974331-88974331,hs11:85617849-85617849;hs11:78148643-78148643,hs11:88974372-88974372;hs11:133459430-133459430,hs11:59912940-59912940;hs11:56498022-56498022,hs11:88974396-88974396;hs11:77874774-77874774,hs11:57537112-57537112;hs11:88974331-88974331,hs11:85617849-85617849;hs11:80290734-80290734,hs11:61159548-61159548;hs11:57467021-57467021,hs11:59910169-59910169;hs11:133475467-133475467,hs11:56677511-56677511;hs11:56498609-56498609,hs11:86132705-86132705;hs11:133475462-133475462,hs11:77208637-77208637;hs11:56498169-56498169,hs11:88973888-88973888;hs11:78148643-78148643,hs11:88974372-88974372;hs11:57533945-57533945,hs11:61745365-61745365;hs11:92388919-92388919,hs11:93275376-93275376;hs11:88671613-88671613,hs11:62464596-62464596;hs11:86133004-86133004,hs11:88973932-88973932;hs11:92388919-92388919,hs11:93275376-93275376;hs11:88974350-88974350,hs11:90813909-90813909;hs11:62310777-62310777,hs11:56529059-56529059;hs11:65962745-65962745,hs11:79133521-79133521;hs11:80288993-80288993,hs11:86132390-86132390;hs11:86133004-86133004,hs11:88973932-88973932;hs11:133075932-133075932,hs11:61318507-61318507;hs6:104439597-104439597,hs6:104440200-104440200;hs20:36718918-36718918,hs20:36718843-36718843;hs11:76257799-76257799,hs11:56496718-56496718;hs11:57533945-57533945,hs11:61745365-61745365;hs11:86133004-86133004,hs11:88973932-88973932;hs11:56498022-56498022,hs11:88974396-88974396;hs11:76257799-76257799,hs11:56496718-56496718;hs11:66178052-66178052,hs11:64842811-64842811;hs11:56498169-56498169,hs11:88973888-88973888;hs11:62462371-62462371,hs1:24080193-24080193;hs11:79130183-79130183,hs11:133461683-133461683;hs11:76257799-76257799,hs11:56496718-56496718;hs11:56498022-56498022,hs11:88974396-88974396;hs11:56498609-56498609,hs11:86132705-86132705;hs19:58477128-58477128,hs19:58476480-58476480;hs11:88974280-88974280,hs11:88973839-88973839;hs11:88974330-88974330,hs11:83115906-83115906;hs11:64841369-64841369,hs11:118523767-118523767;hs11:56498169-56498169,hs11:88973888-88973888;hs11:56498022-56498022,hs11:88974396-88974396;hs11:56498609-56498609,hs11:86132705-86132705;hs11:61223391-61223391,hs11:82253742-82253742;hs11:61316664-61316664,hs11:86989226-86989226;hs11:65429801-65429801,hs11:63532010-63532010;hs21:24828945-24828945,hs21:24829265-24829265;hs11:56498169-56498169,hs11:88973888-88973888 SLC22A20;ARMC2;CCDC81_NARS2;C11orf30;TCEB3;C11orf75;PACS1;CTNND1;FAT3;BSCL2_GRM5;CCDC81_TYR;OR8U8;TYR;ZDHHC5;CCDC81;CCDC83;AHNAK;TYR_NARS2;NARS2;SYT7;CCDC81_CCDC83;TMX2-CTNND1;TYR_CCDC83;C11orf30_OR8U8;HNRNPUL2-BSCL2_GRM5;ODZ4;OPCML;RPRD1B_RPRD1B;OR8U8_OR8U8;BSCL2;C19orf18;PHLDB1;TMEM135_SYT7;C11orf95_RELA St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA Members of the nuclear factor-kappaB (NF-kappaB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-kappaB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-kappaB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-kappaB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-kappaB target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma. GRCh37/hg19 EGAS00001000254 Yes C1orf95,RELA;PACS1,ODZ4;PHLDB1,CDCA5 CTDB0170 Research 24553141 Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 2014 Feb 11 Ependymoma Next Generation Sequencing Homo sapiens ST3 Illumina HighSeq chr1:67625082-83788300:-1;chr1:107215337-107219950:-1;chr1:143538601-249240500:1;chr2:188210554-188212008:-1;chr3:50004272-50005960:-1;chr3:182041516-182045507:-1;chr4:108875141-109373478:-1;chr4:109383708-109384629:-1;chr4:109384630-109385237:1;chr4:109385238-109386211:-1;chr4:109386212-109388977:1;chr4:109388978-109390580:1;chr4:109390581-109392568:-1;chr4:109392569-109393500:1;chr4:109393501-109511572:-1;chr4:109511573-151613043:1;chr4:151613044-151632069:-1;chr5:100307271-100307355:-1;chr9:4714201-21901594:-1;chr9:21901595-22025245:-1;chr9:22025246-24430712:-1;chr9:24430713-24432864:-1;chr9:24432865-29916900:-1;chr9:29916901-31587601:1;chr9:31587602-31587699:-1;chr10:79386572-113490323:-1;chr11:48669201-48670070:-1;chr11:57399735-57400563:-1;chr11:59439701-59440268:-1;chr11:60105782-60107379:-1;chr11:60375800-60377018:-1;chr11:60377019-60377260:1;chr11:60377261-60543559:-1;chr11:60543560-62531300:-1;chr11:62531401-62531825:-1;chr11:64184367-64185239:-1;chr11:64185240-64791300:-1;chr11:64791384-64791800:-1;chr11:64791901-64799860:-1;chr11:64799861-64802103:-1;chr11:64802104-65088994:-1;chr11:65088995-65254664:-1;chr11:65254665-72042700:-1;chr11:72042801-72043094:-1;chr11:78798885-81003016:-1;chr11:81003017-81637490:1;chr11:81637491-81637738:1;chr11:81637739-81637836:1;chr11:81637837-83173785:-1;chr11:83565352-83566601:-1;chr11:88046595-88047613:-1;chr11:89831401-92099860:-1;chr11:94887474-94887888:1;chr11:94887889-94888065:1;chr11:94888066-94888527:1;chr11:94888528-94889981:1;chr11:94889982-94890456:-1;chr11:94890457-94961146:1;chr11:94961147-94962333:-1;chr11:95544046-95545829:-1;chr11:107827417-107952854:-1;chr11:111488261-111489062:-1;chr11:112270860-112272265:-1;chr11:112272266-114186121:-1;chr11:114186122-114186599:-1;chr11:116176859-116177461:-1;chr11:118812654-118813863:-1;chr11:119214409-119214728:-1;chr11:119214729-119705794:-1;chr11:119705795-119707689:-1;chr11:119912269-119913412:-1;chr11:123281297-125461747:-1;chr11:126349249-126741155:-1;chr11:132339815-132341900:-1;chr13:24806253-24827234:-1;chr14:19000101-34303789:1;chr14:34303790-34757423:-1;chr16:7865401-21594700:-1;chr17:1-2032200:1;chr17:28952501-30579648:1;chr17:30579649-32071800:1;chr17:32071801-32101473:1;chr17:32101474-34968606:1;chr18:49080713-49080811:-1 hs7:142998405-142998405,hs15:72276914-72276914;hs1:107215337-107215337,hs1:107219951-107219951;hs1:67625082-67625082,hs1:83788301-83788301;hs11:114186122-114186122,hs11:114186600-114186600;hs11:48669026-48669026,hs11:48670071-48670071;hs7:142998405-142998405,hs15:72276914-72276914;hs9:3123766-3123766,hs9:3123836-3123836;hs4:108877071-108877071,hs4:109384630-109384630;hs15:72276908-72276908,hs7:142998123-142998123;hs11:119214729-119214729,hs11:88047614-88047614;hs11:81637739-81637739,hs11:119707690-119707690;hs9:132014196-132014196,hs9:133525332-133525332;hs11:94887474-94887474,hs11:60377019-60377019;hs2:38306620-38306620,hs2:46717347-46717347;hs11:72042738-72042738,hs11:83566602-83566602;hs11:60105782-60105782,hs11:83565352-83565352;hs11:95544046-95544046,hs11:116177462-116177462;hs2:188210554-188210554,hs2:188212009-188212009;hs18:49080713-49080713,hs18:49080812-49080812;hs6:74110830-74110830,hs2:24763984-24763984;hs11:119214729-119214729,hs11:88047614-88047614;hs11:132341901-132341901,hs11:65254665-65254665;hs11:123281297-123281297,hs11:126349249-126349249;hs11:64184367-64184367,hs11:65088995-65088995;hs19:45622885-45622885,hs19:45622982-45622982;hs4:109386212-109386212,hs4:109373479-109373479;hs4:109385238-109385238,hs4:109511573-109511573;hs11:81637837-81637837,hs11:67359965-67359965;hs15:72276908-72276908,hs7:142998123-142998123;hs11:118812654-118812654,hs11:118813864-118813864;hs9:24430713-24430713,hs9:24432865-24432865;hs5:57769180-57769180,hs5:59079665-59079665;hs11:71621464-71621464,hs11:112272266-112272266;hs11:94888600-94888600,hs11:119214409-119214409;hs3:50005961-50005961,hs17:34889458-34889458;hs14:37151721-37151721,hs14:37151782-37151782;hs9:31587602-31587602,hs9:31587700-31587700;hs17:45569813-45569813,hs8:11787247-11787247;hs10:79386572-79386572,hs10:113490324-113490324;hs11:57399735-57399735,hs11:57400564-57400564;hs11:107827417-107827417,hs11:83173786-83173786;hs11:64799861-64799861,hs11:81637491-81637491;hs11:62531311-62531311,hs11:72043095-72043095;hs3:110372617-110372617,hs3:110372657-110372657;hs11:94888600-94888600,hs11:119214409-119214409;hs11:59439608-59439608,hs11:59440269-59440269;hs9:21901595-21901595,hs9:22025246-22025246;hs9:133525306-133525306,hs2:29004208-29004208;hs11:39887039-39887039,hs11:39887269-39887269;hs17:30579649-30579649,hs17:28951909-28951909;hs7:142998395-142998395,hs15:72276914-72276914;hs12:122342961-122342961,hs12:57917215-57917215;hs11:62531311-62531311,hs11:72043095-72043095;hs3:182041516-182041516,hs3:182045508-182045508;hs3:77984982-77984982,hs3:77984926-77984926;hs2:24763977-24763977,hs6:74110832-74110832;hs10:90471894-90471894,hs10:90428535-90428535;hs11:107827417-107827417,hs11:83173786-83173786;hs11:112270860-112270860,hs11:64791849-64791849;hs13:24806253-24806253,hs13:24827235-24827235;hs11:64799861-64799861,hs11:81637491-81637491;hs11:125461748-125461748,hs11:60107380-60107380;hs2:106475471-106475471,hs4:75849999-75849999;hs11:64791384-64791384,hs11:64802104-64802104;hs11:94962334-94962334,hs11:92099861-92099861;hs4:108875141-108875141,hs4:109383708-109383708;hs11:78798885-78798885,hs11:94887531-94887531;hs7:142998113-142998113,hs7:142998403-142998403;hs11:88046595-88046595,hs11:111488261-111488261;hs12:122342961-122342961,hs12:57917215-57917215;hs11:94887827-94887827,hs11:107952855-107952855;hs11:119214729-119214729,hs11:88047614-88047614;hs11:60105782-60105782,hs11:83565352-83565352;hs4:151613044-151613044,hs4:151632070-151632070;hs11:94888066-94888066,hs11:64185240-64185240;hs11:119705795-119705795,hs11:81003017-81003017;hs3:85646546-85646546,hs3:69873613-69873613;hs7:142998405-142998405,hs15:72276914-72276914;hs11:119912269-119912269,hs11:126741156-126741156;hs11:116176859-116176859,hs11:111489063-111489063;hs5:27443337-27443337,hs5:27443440-27443440;hs11:67373086-67373086,hs11:95545830-95545830;hs22:33661576-33661576,hs22:33661660-33661660;hs11:107827417-107827417,hs11:83173786-83173786;hs4:109390581-109390581,hs4:109392569-109392569;hs11:94888016-94888016,hs11:107828960-107828960;hs11:94961147-94961147,hs11:65433038-65433038;hs5:100307271-100307271,hs5:100307356-100307356;hs11:94887889-94887889,hs11:64634423-64634423;hs17:34886656-34886656,hs3:50004272-50004272;hs14:34303790-34303790,hs14:34757424-34757424;hs11:132339815-132339815,hs11:119913413-119913413;hs3:85646546-85646546,hs3:69873613-69873613;hs15:72276908-72276908,hs7:142998123-142998123;hs16:7106321-7106321,hs16:7106231-7106231;hs12:125506321-125506321,hs12:125506720-125506720;hs11:125459685-125459685,hs11:107828724-107828724;hs11:94890457-94890457,hs11:62531826-62531826;hs11:63531205-63531205,hs11:60543560-60543560 CASP2;MYO9A;MYO9A_MYO9A;CTSC;DLG2_CLPB;MS4A6E_DLG2;CEP57;CALCRL;DDX43;MFRP;OPCML;KIRREL3;CDC42EP2;LOC285456;PDE4D;LOC100133315;MYO19_RBM6;MRPL45P2;KCNMA1;RAB39;ARL2-SNX15;CLPB;C1QTNF5;CDKN2B-AS1;PPP1CB;LRRC37BP1;MBD6;POLR2G;LIPF;SPATA13_SPATA13;SNX15;MS4A6E;NCK2;ARL2-SNX15_ARL2-SNX15;SESN3_FAT3;ODZ4;SIK2_CTSC;PSMD9;CUL5;CADM2;SIK2;DLG2;SESN3;EHD1;RBM6_MYO19;MITF St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA Members of the nuclear factor-kappaB (NF-kappaB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-kappaB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-kappaB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-kappaB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-kappaB target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma. GRCh37/hg19 EGAS00001000254 Yes C1orf95,RELA;KIRREL3,RP11-831A10 CTDB0171 Research 24553141 Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 2014 Feb 2,11 Ependymoma Next Generation Sequencing Homo sapiens ST4 Illumina HighSeq chr2:32150501-32200497:-1;chr2:32850983-32851536:-1;chr2:34130260-34135800:-1;chr2:34654993-34666613:-1;chr2:39763329-39763957:-1;chr3:60201-90391100:-1;chr3:192886401-197948400:-1;chr4:96418001-191043900:1;chr5:11701-45912900:-1;chr5:100762101-180785400:-1;chr6:90701-65194400:-1;chr6:65202301-171050900:-1;chr7:10001-19614100:1;chr8:33501-78414800:-1;chr8:78448301-146303800:-1;chr9:10001-6700600:-1;chr9:6711401-141108100:-1;chr11:50616101-59242474:1;chr11:59242475-59247917:-1;chr11:63613166-63613448:-1;chr11:64429398-64484187:-1;chr13:56114201-115109800:1;chr21:9411201-48119800:-1;chr22:16054601-51234500:-1 hs2:33528011-33528011,hs2:37546802-37546802;hs11:57080811-57080811,hs11:55701486-55701486;hs11:65431243-65431243,hs11:63532315-63532315;hs11:59242475-59242475,hs2:34837578-34837578;hs11:63613166-63613166,hs11:63613449-63613449;hs2:31455656-31455656,hs2:33529265-33529265;hs6:149019988-149019988,hs6:149020049-149020049;hs2:37555137-37555137,hs2:31463551-31463551;hs2:39763958-39763958,hs11:59236125-59236125;hs11:65432268-65432268,hs2:34135762-34135762;hs11:64429398-64429398,hs2:39763329-39763329;hs2:34654993-34654993,hs2:32394770-32394770;hs2:32389918-32389918,hs2:32851537-32851537;hs2:34130260-34130260,hs2:51175100-51175100;hs2:34902878-34902878,hs2:34666614-34666614;hs2:39347009-39347009,hs2:31457120-31457120;hs11:65096960-65096960,hs11:65097953-65097953;hs1:57176418-57176418,hs1:57176469-57176469;hs11:55691545-55691545,hs11:57080302-57080302;hs11:59237569-59237569,hs2:32150351-32150351;hs3:77239677-77239677,hs3:77239792-77239792;hs11:60192521-60192521,hs11:60193197-60193197;hs11:62923912-62923912,hs2:32200498-32200498;hs2:52223302-52223302,hs2:39349632-39349632;hs2:32850983-32850983,hs11:64484188-64484188;hs2:31462408-31462408,hs11:59247918-59247918 LTBP1;TNKS1BP1;C11orf95;EHD3;LOC728730;LOC728730_NRXN2;SLC30A6;NRXN1;SOS1_EHD3;PRKAA2_PRKAA2;MEMO1;NRXN2 St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA Members of the nuclear factor-kappaB (NF-kappaB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-kappaB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-kappaB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-kappaB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-kappaB target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma. GRCh37/hg19 EGAS00001000254 Yes C1orf95,RELA; CTDB0172 Research 24553141 Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 2014 Feb 6,8,11 Ependymoma Next Generation Sequencing Homo sapiens ST5 Illumina HighSeq chr1:120378803-120381148:-1;chr6:2150195-2172900:-1;chr6:2172901-2174800:-1;chr6:2174801-2180017:-1;chr6:3927080-3943200:-1;chr11:63476704-63532899:-1;chr11:65091865-65094547:-1;chrY:2649501-59033300:-1 hs6:2180018-2180018,hs11:65430730-65430730;hs1:120378803-120378803,hs1:120381149-120381149;hs11:63476704-63476704,hs11:65091865-65091865;hs6:3927080-3927080,hs6:3943206-3943206;hs6:2150195-2150195,hs11:65094548-65094548;hs11:63093918-63093918,hs8:50418821-50418821;hs11:65430619-65430619,hs11:63532900-63532900 GMDS;NBPF7_NBPF7;RTN3;C11orf95 St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA Members of the nuclear factor-kappaB (NF-kappaB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-kappaB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-kappaB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-kappaB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-kappaB target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma. GRCh37/hg19 EGAS00001000254 Yes C1orf95,RELA; CTDB0173 Research 24553141 Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 2014 Feb 11 Ependymoma Next Generation Sequencing Homo sapiens ST6 Illumina HighSeq chr1:10101-249240500:-1;chr2:92277301-243183600:-1;chr3:60201-197948400:-1;chr4:10501-191043900:-1;chr5:11701-180375000:1;chr5:180440901-180785400:1;chr6:90701-171050900:-1;chr7:61886701-159128500:-1;chr8:33501-146303800:-1;chr9:10001-141108100:-1;chr11:133701-59887975:-1;chr11:59889851-61609285:-1;chr11:61609694-62624514:-1;chr11:62625097-63993126:-1;chr11:63993645-65431302:-1;chr11:65432736-68208863:-1;chr11:68208864-69354214:-1;chr11:69354215-71247036:-1;chr11:71249201-77358825:-1;chr11:77359102-78565937:-1;chr11:79499844-80280500:-1;chr11:80281436-82077333:-1;chr11:82077540-85582709:-1;chr11:85584876-86883342:-1;chr11:86884365-90519953:-1;chr11:90521007-134926900:-1;chr14:19000101-107289500:-1;chr18:10001-78017200:-1;chr20:60001-62965000:-1;chr22:16054601-51234500:-1;chrX:2699501-154930300:-1 hs11:71247037-71247037,hs11:61609694-61609694;hs11:77358826-77358826,hs11:85584876-85584876;hs11:65431303-65431303,hs11:63532061-63532061;hs11:62624515-62624515,hs11:80280644-80280644;hs11:71249048-71249048,hs11:59889851-59889851;hs11:90521007-90521007,hs11:77359102-77359102;hs11:78565938-78565938,hs11:86883343-86883343;hs9:138166501-138166501,hs9:138166442-138166442;hs11:63528854-63528854,hs11:86884365-86884365;hs22:49276093-49276093,hs22:49275975-49275975;hs11:82077540-82077540,hs11:80281436-80281436;hs19:21005728-21005728,hs19:21005944-21005944;hs11:63993127-63993127,hs11:62123694-62123694;hs11:79499844-79499844,hs11:69354215-69354215;hs5:70763497-70763497,hs5:70764157-70764157;hs11:59887976-59887976,hs11:85582710-85582710;hs5:91502446-91502446,hs5:91502530-91502530;hs11:62123343-62123343,hs11:82077334-82077334;hs11:68208864-68208864,hs11:90519954-90519954;hs11:63993127-63993127,hs11:62123694-62123694;hs11:65432736-65432736,hs11:63993645-63993645;hs11:61609286-61609286,hs11:62625097-62625097 sFADS2;CCDC83;C11orf95;SLC3A2;TMEM135_ODZ4;TMEM135;ASRGL1;BDP1;LRP5;TRPT1;FADS2_SLC3A2 St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA Members of the nuclear factor-kappaB (NF-kappaB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-kappaB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-kappaB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-kappaB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-kappaB target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma. GRCh37/hg19 EGAS00001000254 Yes C1orf95,RELA; CTDB0174 Research 24553141 Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 2014 Feb 6,11 Ependymoma Next Generation Sequencing Homo sapiens ST7 Illumina HighSeq chr2:61586301-61779500:-1;chr3:97275094-97283404:-1;chr4:63432036-63432100:1;chr5:164888567-164995689:-1;chr7:79979905-79979984:1;chr7:159103401-159128500:1;chr9:21333545-24963469:-1 hs11:62493322-62493322,hs11:65384107-65384107;hs11:54928254-54928254,hs11:54929101-54929101;hs9:21333545-21333545,hs9:24963470-24963470;hs3:97275094-97275094,hs3:97283405-97283405;hs11:65384119-65384119,hs6:3457860-3457860;hs11:62493322-62493322,hs11:65384107-65384107;hs11:65430839-65430839,hs11:63533129-63533129;hs11:63533000-63533000,hs11:62493318-62493318;hs16:12002319-12002319,hs16:12002645-12002645;hs5:164888567-164888567,hs5:164995690-164995690;hs11:62493322-62493322,hs11:65384107-65384107;hs7:79979985-79979985,hs7:79979905-79979905;hs11:63533000-63533000,hs11:62493318-62493318;hs11:63533000-63533000,hs11:62493318-62493318;hs18:45333973-45333973,hs1:178469117-178469117;hs11:62572909-62572909,hs6:35436603-35436603;hs4:63432159-63432159,hs4:63432036-63432036;hs11:62572909-62572909,hs6:35436603-35436603;hs11:62493322-62493322,hs11:65384107-65384107;hs6:3457888-3457888,hs11:65430842-65430842 PCNXL3;HNRNPUL2;HNRNPUL2-BSCL2_C11orf95;C11orf95;HNRNPUL2_C11orf95;RPL10A;NXF1;HNRNPUL2-BSCL2 St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA Members of the nuclear factor-kappaB (NF-kappaB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-kappaB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-kappaB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-kappaB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-kappaB target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma. GRCh37/hg19 EGAS00001000254 Yes C1orf95,RELA; CTDB0175 Research 24553141 Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 2014 Feb 11 Ependymoma Next Generation Sequencing Homo sapiens ST8 Illumina HighSeq chr2:10001-81600:1;chr3:60201-187500:1;chr7:159106701-159128500:1;chr11:1282285-1283001:-1;chr11:44546631-44546759:-1;chr11:65226635-65226761:-1;chr11:65431401-65432927:-1;chr11:134893601-134946400:1;chr14:107216201-107289500:1;chr18:77999101-78017200:1 hs11:1282285-1282285,hs11:44546760-44546760;hs11:44546631-44546631,hs11:63532380-63532380;hs11:65226763-65226763,hs11:65432928-65432928;hs11:1481510-1481510,hs11:1482374-1482374;hs11:65226635-65226635,hs11:1283002-1283002;hs11:65431350-65431350,hs11:63532607-63532607 MUC5B;C11orf95;BRSK2 St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA Members of the nuclear factor-kappaB (NF-kappaB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-kappaB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-kappaB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-kappaB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-kappaB target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma. GRCh37/hg19 EGAS00001000254 Yes C1orf95,RELA; CTDB0176 Research 24553141 Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 2014 Feb 4,11 Ependymoma Next Generation Sequencing Homo sapiens ST16 Illumina HighSeq chr1:81217101-81237400:-1;chr1:98589401-98654300:-1;chr2:59847801-59874500:-1;chr2:108558401-108583500:-1;chr2:139818501-139848900:-1;chr3:79636601-79660200:-1;chr3:168690401-168722700:-1;chr4:46101501-46124200:-1;chr4:117824865-117827924:-1;chr5:102843880-102847057:-1;chr6:22580203-22599200:-1;chr10:25623101-25665700:-1;chr10:57239213-57269300:-1;chr11:50539301-50543138:1;chr11:50547301-50566700:-1;chr11:50567567-56288679:-1;chr11:56288680-56289476:-1;chr11:57745112-57745285:-1;chr11:59235143-62303918:-1;chr11:91405151-91405481:-1;chr11:94930463-94931480:-1;chr11:104878828-104879567:-1;chr11:113887101-113887569:-1;chr11:116173026-116173734:-1;chr12:82104001-82131200:-1;chr12:88263601-88271326:-1;chr12:88271390-88290300:-1;chr14:19000101-20208100:-1;chr14:62772301-62808000:-1;chr18:58463901-58490800:-1;chrY:2649501-59033300:-1 hs11:124223124-124223124,hs11:124238938-124238938;hs4:117824865-117824865,hs4:117827925-117827925;hs4:117888344-117888344,hs4:117920171-117920171;hs11:120951839-120951839,hs11:94931481-94931481;hs5:103793701-103793701,hs5:104042547-104042547;hs11:113887570-113887570,hs11:57745286-57745286;hs11:59235143-59235143,hs11:91405482-91405482;hs11:101981768-101981768,hs11:63530974-63530974;hs11:56288680-56288680,hs11:57745112-57745112;hs11:91405151-91405151,hs11:121006568-121006568;hs11:116173026-116173026,hs11:121006909-121006909;hs4:170778649-170778649,hs4:170778917-170778917;hs2:97835742-97835742,hs2:96600330-96600330;hs5:102843880-102843880,hs5:102847058-102847058;hs11:113887041-113887041,hs11:76925957-76925957;hs11:116173735-116173735,hs11:62303919-62303919;hs11:76924222-76924222,hs11:94930463-94930463;hs11:117895034-117895034,hs11:56289477-56289477;hs11:104878828-104878828,hs11:104879568-104879568;hs4:182472980-182472980,hs11:112813940-112813940 SESN3_TBCEL;C11orf95_YAP1;OR8U8;TECTA;ANKRD36;AHNAK;MYO7A_SESN3;LOC100526771_OR8U8;CASP5_CASP5 St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project, Memphis, Tennessee 38105, USA Members of the nuclear factor-kappaB (NF-kappaB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-kappaB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-kappaB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-kappaB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-kappaB target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma. GRCh37/hg19 EGAS00001000254 Yes C11orf95,YAP1;MYO7A,SESN3 CTDB0177 Research 24670643 Li Y, Schwab C, Ryan SL, Papaemmanuil E, Robinson HM, Jacobs P, Moorman AV, Dyer S, Borrow J, Griffiths M, Heerema NA, Carroll AJ, Talley P, Bown N, Telford N, Ross FM, Gaunt L, McNally RJ, Young BD, Sinclair P, Rand V, Teixeira MR, Joseph O, Robinson B, Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 2014 Apr 15,21 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens PD9020a Illumina HiSeq 2000 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes. GRCh37/hg19 EGAD00001000658 Yes NA CTDB0178 Research 24670643 Li Y, Schwab C, Ryan SL, Papaemmanuil E, Robinson HM, Jacobs P, Moorman AV, Dyer S, Borrow J, Griffiths M, Heerema NA, Carroll AJ, Talley P, Bown N, Telford N, Ross FM, Gaunt L, McNally RJ, Young BD, Sinclair P, Rand V, Teixeira MR, Joseph O, Robinson B, Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 2014 Apr 21 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens PD9021a Illumina HiSeq 2000 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes. GRCh37/hg19 EGAD00001000658 Yes NA CTDB0179 Research 24670643 Li Y, Schwab C, Ryan SL, Papaemmanuil E, Robinson HM, Jacobs P, Moorman AV, Dyer S, Borrow J, Griffiths M, Heerema NA, Carroll AJ, Talley P, Bown N, Telford N, Ross FM, Gaunt L, McNally RJ, Young BD, Sinclair P, Rand V, Teixeira MR, Joseph O, Robinson B, Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 2014 Apr 21 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens PD9022a Illumina HiSeq 2000 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes. GRCh37/hg19 EGAD00001000658 Yes NA CTDB0180 Research 24670643 Li Y, Schwab C, Ryan SL, Papaemmanuil E, Robinson HM, Jacobs P, Moorman AV, Dyer S, Borrow J, Griffiths M, Heerema NA, Carroll AJ, Talley P, Bown N, Telford N, Ross FM, Gaunt L, McNally RJ, Young BD, Sinclair P, Rand V, Teixeira MR, Joseph O, Robinson B, Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 2014 Apr 21 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens PD9023a Illumina HiSeq 2000 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes. GRCh37/hg19 EGAD00001000658 Yes NA CTDB0181 Research 24670643 Li Y, Schwab C, Ryan SL, Papaemmanuil E, Robinson HM, Jacobs P, Moorman AV, Dyer S, Borrow J, Griffiths M, Heerema NA, Carroll AJ, Talley P, Bown N, Telford N, Ross FM, Gaunt L, McNally RJ, Young BD, Sinclair P, Rand V, Teixeira MR, Joseph O, Robinson B, Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 2014 Apr 21 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens PD4117a Illumina HiSeq 2000 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes. GRCh37/hg19 EGAD00001000658 Yes NA CTDB0182 Research 24670643 Li Y, Schwab C, Ryan SL, Papaemmanuil E, Robinson HM, Jacobs P, Moorman AV, Dyer S, Borrow J, Griffiths M, Heerema NA, Carroll AJ, Talley P, Bown N, Telford N, Ross FM, Gaunt L, McNally RJ, Young BD, Sinclair P, Rand V, Teixeira MR, Joseph O, Robinson B, Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 2014 Apr 15,21 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens PD7170a Illumina HiSeq 2000 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes. GRCh37/hg19 EGAD00001000658 Yes NA CTDB0183 Research 24670643 Li Y, Schwab C, Ryan SL, Papaemmanuil E, Robinson HM, Jacobs P, Moorman AV, Dyer S, Borrow J, Griffiths M, Heerema NA, Carroll AJ, Talley P, Bown N, Telford N, Ross FM, Gaunt L, McNally RJ, Young BD, Sinclair P, Rand V, Teixeira MR, Joseph O, Robinson B, Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 2014 Apr 15,21 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens PD7171a Illumina HiSeq 2000 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes. GRCh37/hg19 EGAD00001000658 Yes NA CTDB0184 Research 24670643 Li Y, Schwab C, Ryan SL, Papaemmanuil E, Robinson HM, Jacobs P, Moorman AV, Dyer S, Borrow J, Griffiths M, Heerema NA, Carroll AJ, Talley P, Bown N, Telford N, Ross FM, Gaunt L, McNally RJ, Young BD, Sinclair P, Rand V, Teixeira MR, Joseph O, Robinson B, Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 2014 Apr 15,21 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens PD10008a Illumina HiSeq 2000 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes. GRCh37/hg19 EGAD00001000658 Yes NA CTDB0185 Research 24670643 Li Y, Schwab C, Ryan SL, Papaemmanuil E, Robinson HM, Jacobs P, Moorman AV, Dyer S, Borrow J, Griffiths M, Heerema NA, Carroll AJ, Talley P, Bown N, Telford N, Ross FM, Gaunt L, McNally RJ, Young BD, Sinclair P, Rand V, Teixeira MR, Joseph O, Robinson B, Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 2014 Apr 15,21 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens PD10009a Illumina HiSeq 2000 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes. GRCh37/hg19 EGAD00001000658 Yes NA CTDB0186 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 13,20 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0384 Illumina HiSeq 2000 hs1:9476437-9476437,hs3:96604245-96604245;hs1:77465422-77465422,hs6:82454489-82454489;hs1:101437413-101437413,hs1:101439416-101439416;hs1:106664304-106664304,hs1:106668260-106668260;hs1:108136719-108136719,hs1:108137232-108137232;hs1:159494606-159494606,hs4:99513697-99513697;hs1:246929463-246929463,hs1:246388678-246388678;hs2:22962218-22962218,hs2:23393425-23393425;hs2:88864150-88864150,hs2:88864208-88864208;hs2:133001428-133001428,hs14:19000172-19000172;hs2:146252246-146252246,hs2:806491-806491;hs3:11685085-11685085,hs3:178469137-178469137;hs3:18672577-18672577,hs3:20113942-20113942;hs3:59753449-59753449,hs3:59972822-59972822;hs3:65197426-65197426,hs3:65217670-65217670;hs3:85051425-85051425,hs16:79737202-79737202;hs3:123590928-123590928,hs20:51491435-51491435;hs3:135980778-135980778,hs3:135980875-135980875;hs3:176537593-176537593,hs3:176592803-176592803;hs3:176545416-176545416,hs3:176837941-176837941;hs3:179061946-179061946,hs3:12009978-12009978;hs3:190688115-190688115,hs3:191079961-191079961;hs3:193452855-193452855,hs3:193556172-193556172;hs3:196513380-196513380,hs3:196513442-196513442;hs4:12944727-12944727,hs4:12948594-12948594;hs4:29828473-29828473,hs4:29830855-29830855;hs4:95476207-95476207,hs12:53342905-53342905;hs4:130106855-130106855,hs4:130395005-130395005;hs5:10301537-10301537,hs6:31803104-31803104;hs5:24746046-24746046,hs5:25559214-25559214;hs5:37991456-37991456,hs20:33590230-33590230;hs5:99507374-99507374,hs5:99507665-99507665;hs5:165041644-165041644,hs5:165482374-165482374;hs5:175878829-175878829,hs18:41279290-41279290;hs6:5135295-5135295,hs6:5135740-5135740;hs6:18415524-18415524,hs6:18499313-18499313;hs6:31807531-31807531,hs5:10301536-10301536;hs6:33536236-33536236,hs6:33552099-33552099;hs6:33551997-33551997,hs6:37654125-37654125;hs6:34607332-34607332,hs20:51346764-51346764;hs6:36607480-36607480,hs13:78327134-78327134;hs6:37672999-37672999,hs13:59740798-59740798;hs6:37673083-37673083,hs13:59736389-59736389;hs6:54036238-54036238,hs6:54094214-54094214;hs6:64142114-64142114,hs8:50851121-50851121;hs6:123849869-123849869,hs6:71842981-71842981;hs6:146149490-146149490,hs10:2297811-2297811;hs6:146611914-146611914,hs10:3754697-3754697;hs6:157962215-157962215,hsY:17539065-17539065;hs7:6307677-6307677,hs12:29621014-29621014;hs7:16831543-16831543,hs15:48427676-48427676;hs7:84381808-84381808,hs7:84381670-84381670;hs7:110452678-110452678,hs7:109849168-109849168;hs7:126762756-126762756,hs7:106505327-106505327;hs7:136784013-136784013,hs7:136785152-136785152;hs8:6362735-6362735,hs8:118317432-118317432;hs8:34764794-34764794,hs8:35329986-35329986;hs8:49155386-49155386,hs8:49155689-49155689;hs8:51130002-51130002,hs8:51766364-51766364;hs8:57449366-57449366,hs11:9339506-9339506;hs8:85865360-85865360,hs8:85874160-85874160;hs8:126681536-126681536,hs13:78932591-78932591;hs8:144154617-144154617,hs8:144153627-144153627;hs9:33523770-33523770,hs2:133115893-133115893;hs10:57044497-57044497,hs10:57069416-57069416;hs10:129647123-129647123,hs9:10208237-10208237;hs11:3929702-3929702,hs11:3844028-3844028;hs11:9554048-9554048,hs11:9554356-9554356;hs11:21499308-21499308,hs11:21806763-21806763;hs11:68331242-68331242,hs11:68331983-68331983;hs11:79774427-79774427,hs11:79872454-79872454;hs11:97196046-97196046,hs11:99623376-99623376;hs11:103640503-103640503,hs11:104106633-104106633;hs11:122766019-122766019,hs11:123282129-123282129;hs12:156186-156186,hs12:69734029-69734029;hs12:6976845-6976845,hs12:6978027-6978027;hs12:24852785-24852785,hs12:24935201-24935201;hs12:48683417-48683417,hs12:48685277-48685277;hs12:48685605-48685605,hs12:72800764-72800764;hs12:48686574-48686574,hs20:62145285-62145285;hs12:53407130-53407130,hs12:72830757-72830757;hs12:54323036-54323036,hs20:43236044-43236044;hs12:54381260-54381260,hs20:62819186-62819186;hs12:55698548-55698548,hs20:53195539-53195539;hs12:62588296-62588296,hs20:62148982-62148982;hs12:62723651-62723651,hs20:61347848-61347848;hs12:62906258-62906258,hs20:56181624-56181624;hs12:62914146-62914146,hs12:70162474-70162474;hs12:63044683-63044683,hs20:57025238-57025238;hs12:63191013-63191013,hs13:59081537-59081537;hs12:63273351-63273351,hs13:28146630-28146630;hs12:63281274-63281274,hs20:51395054-51395054;hs12:63311610-63311610,hs20:56499804-56499804;hs12:63375183-63375183,hs20:52911178-52911178;hs12:63481902-63481902,hs13:52735303-52735303;hs12:63481924-63481924,hs13:30029577-30029577;hs12:63493040-63493040,hs12:71518069-71518069;hs12:63520309-63520309,hs13:29178787-29178787;hs12:63654110-63654110,hs20:52131143-52131143;hs12:63655165-63655165,hs13:74576474-74576474;hs12:63923307-63923307,hs13:59585982-59585982;hs12:63963433-63963433,hs20:53333965-53333965;hs12:64182226-64182226,hs20:54251592-54251592;hs12:64183097-64183097,hs12:64652771-64652771;hs12:64184340-64184340,hs12:70086630-70086630;hs12:64184364-64184364,hs20:61528616-61528616;hs12:64263088-64263088,hs12:64377018-64377018;hs12:64267845-64267845,hs20:61528345-61528345;hs12:64270346-64270346,hs13:29777528-29777528;hs12:64298714-64298714,hs12:65187284-65187284;hs12:64379443-64379443,hs12:74443360-74443360;hs12:64654182-64654182,hs20:61529427-61529427;hs12:64833459-64833459,hs13:30278388-30278388;hs12:64921706-64921706,hs17:39436374-39436374;hs12:65121270-65121270,hs13:62400487-62400487;hs12:65125229-65125229,hs12:65176453-65176453;hs12:65187755-65187755,hs13:62400470-62400470;hs12:65218422-65218422,hs12:69728650-69728650;hs12:65224345-65224345,hs13:74792788-74792788;hs12:65860422-65860422,hs12:66361472-66361472;hs12:67632186-67632186,hs13:28123978-28123978;hs12:67946243-67946243,hs13:77603136-77603136;hs12:68282256-68282256,hs13:27630875-27630875;hs12:68611267-68611267,hs20:55048330-55048330;hs12:68611563-68611563,hs12:68611144-68611144;hs12:68611563-68611563,hs12:68611144-68611144;hs12:68714324-68714324,hs20:51681007-51681007;hs12:68718229-68718229,hs12:68920538-68920538;hs12:68749719-68749719,hs20:57082401-57082401;hs12:68771231-68771231,hs20:53900289-53900289;hs12:68775239-68775239,hs12:68793242-68793242;hs12:68793263-68793263,hs12:72600222-72600222;hs12:68793619-68793619,hs13:27621531-27621531;hs12:68873460-68873460,hs13:28146863-28146863;hs12:68986522-68986522,hs12:70636561-70636561;hs12:69065558-69065558,hs20:51733197-51733197;hs12:69263211-69263211,hs12:68718070-68718070;hs12:69346234-69346234,hs13:56286185-56286185;hs12:69387147-69387147,hs12:69737712-69737712;hs12:69396332-69396332,hs12:74334392-74334392;hs12:69512347-69512347,hs20:50906991-50906991;hs12:69679841-69679841,hs20:51170329-51170329;hs12:69726572-69726572,hs20:51348698-51348698;hs12:69779128-69779128,hs20:51513402-51513402;hs12:69822045-69822045,hs12:69794067-69794067;hs12:69822366-69822366,hs20:56353878-56353878;hs12:69848025-69848025,hs13:78142848-78142848;hs12:69959774-69959774,hs13:74996592-74996592;hs12:69998326-69998326,hs20:52432580-52432580;hs12:70007563-70007563,hs12:69237620-69237620;hs12:70033043-70033043,hs13:58444684-58444684;hs12:70072740-70072740,hs13:77834007-77834007;hs12:70087382-70087382,hs20:51802974-51802974;hs12:70087828-70087828,hs13:29725354-29725354;hs12:70166992-70166992,hs17:36933980-36933980;hs12:70219823-70219823,hs20:52203205-52203205;hs12:70500748-70500748,hs20:54244950-54244950;hs12:70505465-70505465,hs12:67938966-67938966;hs12:70649397-70649397,hs12:70649557-70649557;hs12:70661663-70661663,hs20:55989651-55989651;hs12:70670343-70670343,hs20:50817329-50817329;hs12:70843623-70843623,hs13:53915181-53915181;hs12:71249513-71249513,hs20:62874267-62874267;hs12:71284453-71284453,hs12:54824391-54824391;hs12:71399935-71399935,hs13:65963415-65963415;hs12:71691903-71691903,hs20:62210913-62210913;hs12:72061770-72061770,hs13:28106231-28106231;hs12:72108338-72108338,hs12:81317851-81317851;hs12:72600242-72600242,hs13:79403289-79403289;hs12:72651451-72651451,hs20:62558679-62558679;hs12:72660683-72660683,hs20:56569313-56569313;hs12:72799273-72799273,hs12:75104770-75104770;hs12:72800700-72800700,hs13:83222273-83222273;hs12:74040086-74040086,hs20:50640031-50640031;hs12:74069819-74069819,hs20:53900910-53900910;hs12:74288274-74288274,hs12:83536936-83536936;hs12:74522768-74522768,hs12:81315999-81315999;hs12:74613935-74613935,hs12:83529538-83529538;hs12:75232249-75232249,hs13:59988333-59988333;hs12:75496144-75496144,hs13:78128888-78128888;hs12:75511458-75511458,hs13:27362414-27362414;hs12:75518505-75518505,hs13:78905113-78905113;hs12:75534369-75534369,hs13:77982429-77982429;hs12:81317817-81317817,hs18:61662394-61662394;hs12:81321390-81321390,hs12:74128858-74128858;hs12:82983339-82983339,hs12:83444566-83444566;hs12:83217353-83217353,hs12:83445023-83445023;hs12:83366143-83366143,hs18:21354962-21354962;hs12:83447361-83447361,hs18:21306373-21306373;hs12:118681858-118681858,hs12:118841461-118841461;hs13:27621743-27621743,hs20:50640945-50640945;hs13:27661635-27661635,hs17:35750231-35750231;hs13:27819388-27819388,hs13:28800526-28800526;hs13:27964374-27964374,hs12:64252540-64252540;hs13:28128738-28128738,hs13:78898949-78898949;hs13:28146631-28146631,hs13:75129344-75129344;hs13:28411096-28411096,hs13:31829636-31829636;hs13:28510351-28510351,hs13:63223648-63223648;hs13:29080867-29080867,hs13:29905354-29905354;hs13:29299928-29299928,hs13:29312723-29312723;hs13:29399755-29399755,hs13:77496641-77496641;hs13:29524294-29524294,hs20:51681373-51681373;hs13:29642472-29642472,hs20:53887156-53887156;hs13:29642767-29642767,hs13:79370884-79370884;hs13:29687805-29687805,hs20:62576656-62576656;hs13:29724638-29724638,hs13:60031018-60031018;hs13:29730744-29730744,hs20:53847115-53847115;hs13:29778209-29778209,hs20:51803687-51803687;hs13:29784400-29784400,hs20:53191772-53191772;hs13:29787098-29787098,hs20:53845492-53845492;hs13:29795310-29795310,hs20:52399910-52399910;hs13:29899545-29899545,hs13:61847852-61847852;hs13:29993784-29993784,hs17:37368828-37368828;hs13:30385875-30385875,hs20:53607578-53607578;hs13:30397180-30397180,hs20:53473662-53473662;hs13:30407189-30407189,hs13:62913676-62913676;hs13:30477385-30477385,hs12:68874413-68874413;hs13:30645561-30645561,hs13:30988451-30988451;hs13:30672886-30672886,hs13:78559485-78559485;hs13:31037634-31037634,hs13:64936213-64936213;hs13:31129898-31129898,hs13:74579518-74579518;hs13:31695113-31695113,hs12:75511755-75511755;hs13:31895347-31895347,hs13:59979486-59979486;hs13:32525268-32525268,hs12:75086327-75086327;hs13:45763152-45763152,hs13:57940823-57940823;hs13:45801944-45801944,hs13:45839955-45839955;hs13:45880622-45880622,hs13:49882506-49882506;hs13:52231236-52231236,hs13:59891588-59891588;hs13:54717195-54717195,hs20:52493897-52493897;hs13:55410180-55410180,hs13:55411241-55411241;hs13:55411942-55411942,hs20:56652762-56652762;hs13:56440216-56440216,hs17:36770926-36770926;hs13:56518952-56518952,hs20:56931997-56931997;hs13:57181514-57181514,hs20:50689714-50689714;hs13:57641754-57641754,hs13:59463730-59463730;hs13:58028355-58028355,hs13:49826118-49826118;hs13:58525835-58525835,hs13:59555615-59555615;hs13:58562758-58562758,hs13:58425819-58425819;hs13:58562762-58562762,hs13:59569050-59569050;hs13:58564094-58564094,hs13:77638418-77638418;hs13:58888506-58888506,hs13:59741028-59741028;hs13:59339083-59339083,hs13:59568952-59568952;hs13:59837545-59837545,hs20:51384568-51384568;hs13:59994775-59994775,hs13:59995002-59995002;hs13:60038030-60038030,hs20:50553482-50553482;hs13:60039647-60039647,hs13:45766921-45766921;hs13:60142744-60142744,hs13:59058076-59058076;hs13:60268155-60268155,hs20:55824791-55824791;hs13:60344731-60344731,hs20:52229410-52229410;hs13:61173694-61173694,hs13:65101033-65101033;hs13:61925743-61925743,hs20:54076486-54076486;hs13:62346786-62346786,hs13:62410175-62410175;hs13:62346868-62346868,hs13:64076886-64076886;hs13:62414351-62414351,hs13:59460010-59460010;hs13:62415895-62415895,hs13:62412097-62412097;hs13:62919564-62919564,hs13:74766776-74766776;hs13:62919564-62919564,hs13:74766773-74766773;hs13:63236300-63236300,hs13:78285040-78285040;hs13:64076911-64076911,hs13:57612325-57612325;hs13:64404859-64404859,hs20:56995369-56995369;hs13:64929039-64929039,hs13:64935874-64935874;hs13:67956078-67956078,hs13:62414427-62414427;hs13:69913177-69913177,hs13:69915236-69915236;hs13:74553610-74553610,hs13:74754466-74754466;hs13:74766684-74766684,hs13:74766767-74766767;hs13:74770614-74770614,hs20:51394154-51394154;hs13:74770764-74770764,hs20:52272353-52272353;hs13:74897305-74897305,hs20:53438799-53438799;hs13:75126481-75126481,hs20:51389521-51389521;hs13:75143166-75143166,hs20:56353839-56353839;hs13:75255952-75255952,hs20:53438502-53438502;hs13:77597948-77597948,hs20:52244417-52244417;hs13:77603117-77603117,hs20:53511771-53511771;hs13:78088547-78088547,hs20:52159358-52159358;hs13:78327091-78327091,hs20:56661666-56661666;hs13:78339408-78339408,hs6:34105820-34105820;hs13:78396610-78396610,hs20:51591741-51591741;hs13:78982214-78982214,hs13:59919773-59919773;hs13:78993812-78993812,hs12:68974200-68974200;hs13:79028330-79028330,hs20:51320120-51320120;hs13:79104157-79104157,hs17:37179051-37179051;hs13:79132442-79132442,hs13:29698854-29698854;hs13:79158033-79158033,hs20:62814491-62814491;hs13:79165305-79165305,hs20:51685823-51685823;hs13:79307529-79307529,hs20:51601833-51601833;hs13:79370060-79370060,hs20:53885404-53885404;hs13:79425926-79425926,hs20:62788312-62788312;hs13:81068877-81068877,hs20:61464873-61464873;hs13:81136503-81136503,hs20:57406314-57406314;hs13:83007551-83007551,hs20:43767831-43767831;hs13:83548180-83548180,hs20:53206905-53206905;hs13:113707309-113707309,hs5:124790469-124790469;hs15:59213701-59213701,hs15:71173864-71173864;hs16:59248354-59248354,hs16:84056688-84056688;hs17:36405343-36405343,hs20:53305198-53305198;hs17:37363022-37363022,hs17:38669211-38669211;hs17:38205883-38205883,hs17:38434274-38434274;hs17:38456897-38456897,hs13:54775691-54775691;hs17:38674998-38674998,hs20:51421237-51421237;hs17:38729524-38729524,hs20:56505852-56505852;hs17:68496261-68496261,hs17:69005060-69005060;hs17:68603441-68603441,hs17:68603850-68603850;hs18:22936987-22936987,hs12:83539919-83539919;hs18:25859600-25859600,hs12:83178431-83178431;hs18:60308718-60308718,hs18:60310648-60310648;hs18:65209069-65209069,hs18:25858516-25858516;hs19:40187675-40187675,hs19:37798614-37798614;hs19:47021278-47021278,hs2:228565947-228565947;hs20:15068116-15068116,hs20:15073163-15073163;hs20:49199939-49199939,hs12:51437802-51437802;hs20:50660978-50660978,hs20:51910224-51910224;hs20:50807564-50807564,hs20:55286081-55286081;hs20:50864954-50864954,hs13:56087649-56087649;hs20:51009321-51009321,hs20:53867484-53867484;hs20:51021600-51021600,hs20:55777836-55777836;hs20:51156557-51156557,hs20:51609148-51609148;hs20:51284499-51284499,hs20:52345738-52345738;hs20:51300377-51300377,hs20:51474891-51474891;hs20:51628433-51628433,hs20:56678620-56678620;hs20:51683062-51683062,hs20:56356987-56356987;hs20:51744504-51744504,hs12:68871886-68871886;hs20:51910871-51910871,hs12:74069610-74069610;hs20:51934100-51934100,hs12:69396351-69396351;hs20:52170502-52170502,hs20:55667889-55667889;hs20:52236837-52236837,hs20:56346074-56346074;hs20:52325181-52325181,hs20:55832511-55832511;hs20:52386562-52386562,hs20:53003306-53003306;hs20:52434671-52434671,hs20:54143952-54143952;hs20:52602025-52602025,hs20:51961022-51961022;hs20:53195538-53195538,hs13:29776147-29776147;hs20:53208771-53208771,hs20:59587884-59587884;hs20:53229893-53229893,hs20:62145284-62145284;hs20:53458282-53458282,hs13:78290022-78290022;hs20:53466885-53466885,hs20:55174875-55174875;hs20:53614884-53614884,hs13:27953371-27953371;hs20:53887097-53887097,hs12:68771253-68771253;hs20:54903534-54903534,hs20:60976286-60976286;hs20:55326188-55326188,hs20:57093666-57093666;hs20:55375161-55375161,hs20:57098437-57098437;hs20:55770025-55770025,hs20:56529956-56529956;hs20:55778647-55778647,hs20:56993638-56993638;hs20:55824666-55824666,hs20:51996715-51996715;hs20:55836709-55836709,hs17:38674389-38674389;hs20:56347865-56347865,hs20:51734946-51734946;hs20:56356457-56356457,hs20:56348001-56348001;hs20:56522303-56522303,hs20:56540410-56540410;hs20:56523605-56523605,hs20:55768764-55768764;hs20:56566231-56566231,hs17:36350483-36350483;hs20:56942784-56942784,hs13:64060118-64060118;hs20:56978705-56978705,hs20:55987649-55987649;hs20:61393313-61393313,hs20:55487347-55487347;hs20:61528021-61528021,hs20:61529434-61529434;hs20:61530529-61530529,hs12:70087460-70087460;hs20:61530571-61530571,hs12:64183098-64183098;hs20:61880578-61880578,hs20:62142332-62142332;hs20:62558943-62558943,hs12:68775265-68775265;hs20:62874268-62874268,hs13:79155826-79155826;hs20:62875753-62875753,hs12:63791868-63791868;hs21:15679833-15679833,hs21:15682948-15682948;hsX:6711425-6711425,hsX:6799578-6799578;hsX:63420451-63420451,hsX:63592702-63592702;hsX:64485651-64485651,hsX:64487684-64487684;hsX:94718978-94718978,hs10:31513693-31513693 TSHZ2;MTUS2;BMP7;DIDO1;SRGAP1;TMTC2;DOK5;TBC1D30;PPM1H;TMEM5;IL26;BEST3;KCNC2;LNX2;TRHDE;CNOT2;LIN7A;GTF2F2;SLAIN1;VAPB;KLF12;CPM;MDM1;UBL3;MYT1;FHIT;MACROD2;LAMA3;PCDH15;MLIP;RAB3IP;PPP6R3;PTPRR;SNTG1;EIF2AK3;MON2;VAV3;DIAPH3;SLC30A7;GNS;HMGB1;B3GALTL;MYCBP2;SCEL;RP11-1407O15.2;ZFP64;NTSR1;DNAJC5;PCCB;PAK2;CMBL;LYRM4;C6orf48;GGNBP1;IMMP2L;SMYD3;PTPRD;CADM2;KRT8;C12orf28;EPHA6;NELL1;ZDHHC14;FRS2;PTPN1;PAN3;MYLK;TSPAN8;KCNMB2;HOXC10;CDC6;COL9A3;RAB22A;MSRB3;MED24;RNF144B;PPP5D1;WIPF2;APCDD1L;PKIG;GRM4;MCPH1;KAT2B;RNF111;PI16;VGLL4;FAM19A2;UNC5D;GRM8;ST6GALNAC5;SCCPDH;PGAP2;STIM1;CNTN5;C11orf63;RP11-677C1.2;OVCH1;KRT18;EIF4B;USP15;DPY19L2;XPOT;MDM2;YEATS4;THAP2;TAOK3;SUDS3;USP12;CDADC1;WDFY2;FBXL3;MCF2L;SLC24A5;SLTM;LRRC49;THAP10;SLC38A8;ACACA;TBC1D3;PIP4K2B;STAC2;SLC19A3;MYH7B;TRPC4AP;Z97053.1;ZNF217;BCAS1;RTFDC1;ZBP1;CABLES2;NKAIN4;UCKL1;TBL1XR1;CCDC50;PDLIM5;TSPAN5;FAF2;C6orf106;MDGA1;FAM46A;TRDN;GRM1;CYTH3;AGR2;ANGPT2;FAM123B;MTMR8 Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes MTUS2,UCKL1;MTUS2,STAC2;DIAPH3,BMP7;DOK5,MTUS2;DIDO1,BEST3 CTDB0187 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 17 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0833 Illumina HiSeq 2000 hs1:21275054-21275054,hs5:81869745-81869745;hs1:49834174-49834174,hs1:49876651-49876651;hs1:51767141-51767141,hs1:52509490-52509490;hs1:60896542-60896542,hs22:29065751-29065751;hs1:81315722-81315722,hs5:81869952-81869952;hs1:88589551-88589551,hs1:119875316-119875316;hs1:89026824-89026824,hs22:29066049-29066049;hs1:119400900-119400900,hs6:113124373-113124373;hs1:119401054-119401054,hs7:136910064-136910064;hs1:154211486-154211486,hs17:38679438-38679438;hs1:183595542-183595542,hs11:27780160-27780160;hs1:190737827-190737827,hs22:29065957-29065957;hs1:192751961-192751961,hs1:193168150-193168150;hs1:193129221-193129221,hs1:193283382-193283382;hs1:215482217-215482217,hs5:81870069-81870069;hs1:221594139-221594139,hs1:223139521-223139521;hs1:223087695-223087695,hs1:223155959-223155959;hs1:224322895-224322895,hs1:224201425-224201425;hs1:230860835-230860835,hs1:231153544-231153544;hs1:238046903-238046903,hs1:238317687-238317687;hs1:238512429-238512429,hs1:238513911-238513911;hs1:238964716-238964716,hs1:238965050-238965050;hs1:241135425-241135425,hs1:242422406-242422406;hs1:241455176-241455176,hs1:241688374-241688374;hs2:2229039-2229039,hs2:4048854-4048854;hs2:8545746-8545746,hs2:8621857-8621857;hs2:9627905-9627905,hs2:9628008-9628008;hs2:83500818-83500818,hs2:83502142-83502142;hs2:88206986-88206986,hs5:81869733-81869733;hs2:107465302-107465302,hs5:81870077-81870077;hs2:107465305-107465305,hs5:81869871-81869871;hs2:141869354-141869354,hs2:141996665-141996665;hs2:141986792-141986792,hs2:142169185-142169185;hs2:156552292-156552292,hs2:156558931-156558931;hs2:188821327-188821327,hs22:29065730-29065730;hs2:188821327-188821327,hs22:29066119-29066119;hs2:224097305-224097305,hs2:224097800-224097800;hs2:226113179-226113179,hs2:226943291-226943291;hs2:241090959-241090959,hs2:241575362-241575362;hs3:4683828-4683828,hs3:4620173-4620173;hs3:10035781-10035781,hs3:10089555-10089555;hs3:17637820-17637820,hs3:17753535-17753535;hs3:27887883-27887883,hs22:29065968-29065968;hs3:59946035-59946035,hs3:60056732-60056732;hs3:60318972-60318972,hs3:60481150-60481150;hs3:60358270-60358270,hs3:60369833-60369833;hs3:60528838-60528838,hs3:60569524-60569524;hs3:61150764-61150764,hs3:61151903-61151903;hs3:61624422-61624422,hs3:61834724-61834724;hs3:66009120-66009120,hs3:65997927-65997927;hs3:76513965-76513965,hs3:76584746-76584746;hs3:76606646-76606646,hs3:77004450-77004450;hs3:84972812-84972812,hs3:101284661-101284661;hs3:96922919-96922919,hsX:11732646-11732646;hs3:101284493-101284493,hs3:101284734-101284734;hs3:101284683-101284683,hs10:20442473-20442473;hs3:101284953-101284953,hs8:40701062-40701062;hs3:101285081-101285081,hs16:5546812-5546812;hs3:140860511-140860511,hs3:140860733-140860733;hs3:141085199-141085199,hs3:160347866-160347866;hs3:188060297-188060297,hs3:188128478-188128478;hs3:191929749-191929749,hs22:29065844-29065844;hs4:32530899-32530899,hs11:92879442-92879442;hs4:34577588-34577588,hs20:33099161-33099161;hs4:91871845-91871845,hs4:92213326-92213326;hs4:99920185-99920185,hs4:99927973-99927973;hs4:99920199-99920199,hs4:99928270-99928270;hs4:165535404-165535404,hs14:71198188-71198188;hs4:175910560-175910560,hs4:175912630-175912630;hs4:176589693-176589693,hs4:176715618-176715618;hs4:190777720-190777720,hs4:190778217-190778217;hs5:424510-424510,hs5:424239-424239;hs5:4578991-4578991,hs5:4592952-4592952;hs5:16882433-16882433,hs3:124224499-124224499;hs5:21767310-21767310,hs5:30432065-30432065;hs5:22174446-22174446,hs5:81869821-81869821;hs5:22813210-22813210,hs5:22813652-22813652;hs5:29292807-29292807,hs5:29309373-29309373;hs5:40318856-40318856,hs5:94578934-94578934;hs5:40354842-40354842,hs5:40670282-40670282;hs5:40368802-40368802,hs5:94654078-94654078;hs5:81869880-81869880,hs3:131765615-131765615;hs5:81869938-81869938,hs11:132446214-132446214;hs5:81869952-81869952,hs8:111218518-111218518;hs5:81869972-81869972,hs5:162051107-162051107;hs5:81869972-81869972,hs5:162051107-162051107;hs5:81870075-81870075,hs13:68018935-68018935;hs5:81870077-81870077,hs9:29651190-29651190;hs5:81870077-81870077,hs11:30109978-30109978;hs5:81870077-81870077,hsX:95698368-95698368;hs5:81870077-81870077,hs1:21275034-21275034;hs5:81870078-81870078,hs6:8954174-8954174;hs5:86256166-86256166,hs5:92409749-92409749;hs5:93173251-93173251,hs5:93169108-93169108;hs5:93617811-93617811,hs5:93630494-93630494;hs5:94580829-94580829,hs5:40318681-40318681;hs5:110085922-110085922,hs6:107124692-107124692;hs5:142519293-142519293,hs5:142519127-142519127;hs5:143971743-143971743,hs5:143972686-143972686;hs5:164627860-164627860,hs5:164628767-164628767;hs5:179807288-179807288,hs5:179814628-179814628;hs5:179978179-179978179,hs5:179979164-179979164;hs5:179979168-179979168,hs5:179979357-179979357;hs6:13443690-13443690,hs6:13500418-13500418;hs6:66274846-66274846,hs13:97306316-97306316;hs6:66293871-66293871,hs4:21167219-21167219;hs6:101244499-101244499,hs6:102277883-102277883;hs6:113124712-113124712,hs6:113124730-113124730;hs6:144756803-144756803,hs6:145633381-145633381;hs6:144953240-144953240,hs18:30807102-30807102;hs6:157218325-157218325,hs10:14868123-14868123;hs7:22614799-22614799,hs7:22615834-22615834;hs7:22676218-22676218,hs7:22529606-22529606;hs7:64894133-64894133,hs7:64895080-64895080;hs7:90330355-90330355,hs11:14450871-14450871;hs7:109899436-109899436,hs7:110165987-110165987;hs7:110519845-110519845,hs7:110530679-110530679;hs7:110730267-110730267,hs7:110755528-110755528;hs7:155968441-155968441,hs7:155968695-155968695;hs7:157353157-157353157,hs7:157340220-157340220;hs8:42721557-42721557,hs10:28665096-28665096;hs8:55654422-55654422,hs8:55630064-55630064;hs8:88391152-88391152,hs8:90696212-90696212;hs8:88837304-88837304,hs22:29065729-29065729;hs8:90436320-90436320,hs8:90486429-90486429;hs8:90562033-90562033,hs8:90672488-90672488;hs8:100293433-100293433,hs8:100935079-100935079;hs8:111078634-111078634,hs5:81869951-81869951;hs8:126553773-126553773,hs8:128255945-128255945;hs8:126621612-126621612,hs14:46535300-46535300;hs8:126704506-126704506,hs8:126864806-126864806;hs8:126764614-126764614,hs8:126765763-126765763;hs8:126854835-126854835,hs8:126858858-126858858;hs8:126861044-126861044,hs8:128320483-128320483;hs8:128219630-128219630,hs8:126854848-126854848;hs8:128219630-128219630,hs19:23790723-23790723;hs8:128505558-128505558,hs8:128506269-128506269;hs8:128505558-128505558,hs8:128506269-128506269;hs8:128628171-128628171,hs8:128797772-128797772;hs8:128711625-128711625,hs8:126859381-126859381;hs8:141474178-141474178,hs8:141436937-141436937;hs9:10907949-10907949,hs22:29065718-29065718;hs9:21952644-21952644,hsX:30057998-30057998;hs9:22452375-22452375,hs9:22461755-22461755;hs9:22458332-22458332,hsX:30050421-30050421;hs9:25993012-25993012,hs9:26065422-26065422;hs9:29651198-29651198,hs5:81869956-81869956;hs9:105723670-105723670,hs9:105879859-105879859;hs9:108000833-108000833,hs9:108000120-108000120;hs9:113682350-113682350,hs9:113682481-113682481;hs10:138825-138825,hs10:17420191-17420191;hs10:3224559-3224559,hs10:10719713-10719713;hs10:3227088-3227088,hs10:71255966-71255966;hs10:3246968-3246968,hs10:74609706-74609706;hs10:4885739-4885739,hs10:79145356-79145356;hs10:4900607-4900607,hs10:72212030-72212030;hs10:4916624-4916624,hs10:6120304-6120304;hs10:4921657-4921657,hs10:15024549-15024549;hs10:5598950-5598950,hs10:74097955-74097955;hs10:5614094-5614094,hs10:23957821-23957821;hs10:6123085-6123085,hs10:17206631-17206631;hs10:10729333-10729333,hs10:30233764-30233764;hs10:11855250-11855250,hs10:17205620-17205620;hs10:11855250-11855250,hs11:2658330-2658330;hs10:12017356-12017356,hs10:12023629-12023629;hs10:12017360-12017360,hs10:12020647-12020647;hs10:12017795-12017795,hs10:12023630-12023630;hs10:12020808-12020808,hs10:12016237-12016237;hs10:15031764-15031764,hs10:3244780-3244780;hs10:15235990-15235990,hs10:71981005-71981005;hs10:15247481-15247481,hs10:23963775-23963775;hs10:17441148-17441148,hs10:32456077-32456077;hs10:26179641-26179641,hs10:63004795-63004795;hs10:26877896-26877896,hs10:30845816-30845816;hs10:27269881-27269881,hs10:70867650-70867650;hs10:28870602-28870602,hs9:71474692-71474692;hs10:30241779-30241779,hs10:75666031-75666031;hs10:30858969-30858969,hs10:63353063-63353063;hs10:32458976-32458976,hs10:30647283-30647283;hs10:34744495-34744495,hs10:71962709-71962709;hs10:37715116-37715116,hs10:37718456-37718456;hs10:43835361-43835361,hs10:52148649-52148649;hs10:53746369-53746369,hs10:54030718-54030718;hs10:62544058-62544058,hs10:76645626-76645626;hs10:62703952-62703952,hs10:43623059-43623059;hs10:63052850-63052850,hs10:83370852-83370852;hs10:63344208-63344208,hs10:70842177-70842177;hs10:65701023-65701023,hs10:82701916-82701916;hs10:65701272-65701272,hs10:82703414-82703414;hs10:68480795-68480795,hs10:58434689-58434689;hs10:68695715-68695715,hs10:77032627-77032627;hs10:70847285-70847285,hs10:27259952-27259952;hs10:70872652-70872652,hs10:83820724-83820724;hs10:71983680-71983680,hs10:68686780-68686780;hs10:74145604-74145604,hs10:72199303-72199303;hs10:75690761-75690761,hs10:15670168-15670168;hs10:75956738-75956738,hs10:74586673-74586673;hs10:76658545-76658545,hs10:75902320-75902320;hs10:77059998-77059998,hs10:11840280-11840280;hs10:78528326-78528326,hs10:78530466-78530466;hs10:79147668-79147668,hs10:68452260-68452260;hs10:79726141-79726141,hs10:63137181-63137181;hs10:83821281-83821281,hs10:84036777-84036777;hs10:107981174-107981174,hs10:131375073-131375073;hs11:57579195-57579195,hs11:57578618-57578618;hs11:83828188-83828188,hs11:83855316-83855316;hs11:106440653-106440653,hs11:106442607-106442607;hs12:83389195-83389195,hs12:83426505-83426505;hs12:83389765-83389765,hs12:83445176-83445176;hs12:92255650-92255650,hs12:93162698-93162698;hs12:93957586-93957586,hs12:94042450-94042450;hs12:99543305-99543305,hs22:29065871-29065871;hs13:25604704-25604704,hs13:25604008-25604008;hs13:56551892-56551892,hs13:56553210-56553210;hs13:66811725-66811725,hs13:84026674-84026674;hs13:69212015-69212015,hs22:29066287-29066287;hs13:79513865-79513865,hs13:79604394-79604394;hs13:84034517-84034517,hs13:84257958-84257958;hs13:84034561-84034561,hs13:84034779-84034779;hs13:108095359-108095359,hs13:108095415-108095415;hs13:111326774-111326774,hs16:81803181-81803181;hs14:46019285-46019285,hs14:46016489-46016489;hs14:56662068-56662068,hs14:56670078-56670078;hs14:65174523-65174523,hs14:65132635-65132635;hs14:67441599-67441599,hs5:81869912-81869912;hs14:82909349-82909349,hs14:82897197-82897197;hs14:85454853-85454853,hs14:85414633-85414633;hs14:97330033-97330033,hs14:97329923-97329923;hs15:85727101-85727101,hs15:84921908-84921908;hs15:92852682-92852682,hs15:100927857-100927857;hs15:98073317-98073317,hs15:98074052-98074052;hs16:5546824-5546824,hs3:101284645-101284645;hs16:72496336-72496336,hs16:72496757-72496757;hs17:21319819-21319819,hs17:21320518-21320518;hs17:21319819-21319819,hs17:21320518-21320518;hs17:37714530-37714530,hs17:77318901-77318901;hs17:37993557-37993557,hs17:77223912-77223912;hs17:39374747-39374747,hs17:77822940-77822940;hs17:39818984-39818984,hs17:69585116-69585116;hs17:40883271-40883271,hs17:69570425-69570425;hs17:42470544-42470544,hs17:48267993-48267993;hs17:42474321-42474321,hs17:53066495-53066495;hs17:43295673-43295673,hs17:50849759-50849759;hs17:48209171-48209171,hs17:64476156-64476156;hs17:48268325-48268325,hs17:48270172-48270172;hs17:48276931-48276931,hs17:50792729-50792729;hs17:48409093-48409093,hs17:48738681-48738681;hs17:48491377-48491377,hs17:69521572-69521572;hs17:48502590-48502590,hs17:48205171-48205171;hs17:50205401-50205401,hs17:52857667-52857667;hs17:50804246-50804246,hs17:52844741-52844741;hs17:51861809-51861809,hs17:50592637-50592637;hs17:52573175-52573175,hs17:77906327-77906327;hs17:52573193-52573193,hs17:77906682-77906682;hs17:53626526-53626526,hs17:53628019-53628019;hs17:64251946-64251946,hs17:64251797-64251797;hs17:68130817-68130817,hs17:68131225-68131225;hs17:70402980-70402980,hs17:51448815-51448815;hs17:77354825-77354825,hs17:76313517-76313517;hs17:77906893-77906893,hs17:44296917-44296917;hs18:4006117-4006117,hs18:4285550-4285550;hs18:21462906-21462906,hs18:21463965-21463965;hs18:30809257-30809257,hs6:144953091-144953091;hs18:48509676-48509676,hs18:48604062-48604062;hs19:33087517-33087517,hs19:33087008-33087008;hs19:37145168-37145168,hs19:37162246-37162246;hs19:39012219-39012219,hs19:39012467-39012467;hs19:58829521-58829521,hs19:58868074-58868074;hs20:8584228-8584228,hs20:8580027-8580027;hs20:14384499-14384499,hs20:14501605-14501605;hs20:14799877-14799877,hs20:15000693-15000693;hs20:14823212-14823212,hs20:14917256-14917256;hs20:15083410-15083410,hs20:15098918-15098918;hs20:15185564-15185564,hs20:15977688-15977688;hs21:14345750-14345750,hs21:14345322-14345322;hs21:32645525-32645525,hs21:32647072-32647072;hs21:32748998-32748998,hs21:34801789-34801789;hs22:29065854-29065854,hsX:82884281-82884281;hs22:29065894-29065894,hs9:10907934-10907934;hs22:49780619-49780619,hs22:49779842-49779842;hsX:29970879-29970879,hsX:30058693-30058693;hsX:62934116-62934116,hsX:62956090-62956090;hsX:94110969-94110969,hsX:94196787-94196787;hsX:104065424-104065424,hsX:104119171-104119171;hsX:104508404-104508404,hsX:104543732-104543732;hsX:142713532-142713532,hsX:142713730-142713730;hsX:142714599-142714599,hsX:142721921-142721921;hsX:142722551-142722551,hsX:142714590-142714590;hsX:144665901-144665901,hsX:145124691-145124691;hsX:146356251-146356251,hsX:146348821-146348821;hsY:14010219-14010219,hsY:14010751-14010751 TTC28;FHIT;MACROD2;UPF2;TRMT10C;SLITRK4;IMMP2L;CTNNA3;ROBO2;LRP1B;CDH12;COL1A1;TMTC2;IL1RAPL2;KCNJ12;METAP1;CNOT6;UTRN;TBC1D16;STEAP1B;RBFOX3;DISP1;TIAM1;NRG3;PPA1;FAM190A;PRKG1;PTPRN2;LRRTM3;LAMA3;DLG2;SMAD4;RYR1;FAM155A;KCNMA1;DLGAP1;EYS;ITPR1;PLCB1;RGS7;ARHGAP26;MAGI1;AGBL4;APOH;VRK1;LPAR1;ST8SIA6;CDC73;MCU;KIAA0825;EIF4G3;MCTP1;GPM6A;PTPRG;LPP;TRDMT1;KAT6B;CTNND1;PELI2;KCNJ16;CCDC178;IAH1;ST6GAL2;TBC1D5;SPSB4;AHRR;FAM172A;ARHGEF9;CDK14;KCNIP4;PARD3;MAP3K9;EPHA6;PIP5K1B;CPNE4;ANKS1B;VPS13B;ASCC3;TRAPPC9;KANSL1;KCNQ1;PLXDC2;CNBD1;CA10;OPCML;ADK;MYT1L;RYR2;IL1RAPL1;IKZF3;JUP;RHOBTB1;ZNF675;ABCC3;STXBP4;MICU1;MYO10;ARID1B;GRIK2;RGPD2;GPHN;PRKCA;ZMAT4;KALRN;HS6ST3;FGF12;TTC39A;TXNDC12;UBAP2L;ARPC5;FBXO28;ZP4;PLD5;AKR1E2;CDNF;ITGA8;WAC;MTPAP;RET;SGMS1;CDK1;TSPAN15;NODAL;DNAJB12;AP3M1;MGMT;SLC36A4;PLEKHG7;CARS2;PLEKHG3;PLCG2;EZH1;SAMD14;ELAC1;ZNF461;ZNF497;ITCH;IFNGR2;FANCD2;ZBTB38;SLC25A46;GFOD1;LRRN3;RNF170;DMRTA1 Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes TBC1D16,KANSL1 CTDB0188 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct X Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_1074 Illumina HiSeq 2000 hs1:19130480-19130480,hs19:57755138-57755138;hs1:26839013-26839013,hs1:32513269-32513269;hs1:32549131-32549131,hs1:32550815-32550815;hs1:32966325-32966325,hs1:33005342-33005342;hs1:57220831-57220831,hs19:58361375-58361375;hs1:57221035-57221035,hs19:58358187-58358187;hs1:97395035-97395035,hs1:98271663-98271663;hs1:115364329-115364329,hs1:115481023-115481023;hs1:115400102-115400102,hs1:116429501-116429501;hs1:120471807-120471807,hs1:120249623-120249623;hs1:207386752-207386752,hs1:207459220-207459220;hs1:213608177-213608177,hs1:213594684-213594684;hs1:245816649-245816649,hs1:245827610-245827610;hs1:246095937-246095937,hs1:246135001-246135001;hs2:4530538-4530538,hs17:38004294-38004294;hs2:60954209-60954209,hs2:60955177-60955177;hs2:62649521-62649521,hs4:166445246-166445246;hs2:91937066-91937066,hs12:123873662-123873662;hs2:164071666-164071666,hs19:41566798-41566798;hs2:192154893-192154893,hs2:192155836-192155836;hs2:192491546-192491546,hs2:198422597-198422597;hs2:195548070-195548070,hs2:196503432-196503432;hs2:198393502-198393502,hs2:211938216-211938216;hs2:201620327-201620327,hs2:203635367-203635367;hs2:207128661-207128661,hs2:207129455-207129455;hs2:208655125-208655125,hs2:212550479-212550479;hs2:209219535-209219535,hs2:208159606-208159606;hs2:211678930-211678930,hs2:211680512-211680512;hs3:9921125-9921125,hs3:9930872-9930872;hs3:9922609-9922609,hs3:9944820-9944820;hs3:22595295-22595295,hs3:22595353-22595353;hs3:30336918-30336918,hs3:30818412-30818412;hs3:53162573-53162573,hs7:90396609-90396609;hs3:53162707-53162707,hs7:90398253-90398253;hs3:59959090-59959090,hs3:60035341-60035341;hs3:60239948-60239948,hs3:60472521-60472521;hs3:60431449-60431449,hs3:60476857-60476857;hs3:60485646-60485646,hs3:60511657-60511657;hs3:60879948-60879948,hs3:60910439-60910439;hs3:75960912-75960912,hs11:130675927-130675927;hs3:82826074-82826074,hs3:82826378-82826378;hs3:84262536-84262536,hs3:85001728-85001728;hs3:84987197-84987197,hsX:40607248-40607248;hs3:85001906-85001906,hsX:101788463-101788463;hs3:85284921-85284921,hs3:86294684-86294684;hs3:86183715-86183715,hs3:82826525-82826525;hs3:156069074-156069074,hs3:156130237-156130237;hs3:159985774-159985774,hs3:160058490-160058490;hs3:171833667-171833667,hs3:171837236-171837236;hs3:193710628-193710628,hs3:193465026-193465026;hs4:4554821-4554821,hs4:4558897-4558897;hs4:44840503-44840503,hs4:44838971-44838971;hs4:91046928-91046928,hs4:91050928-91050928;hs4:91047726-91047726,hs4:91264168-91264168;hs4:91050926-91050926,hs4:91053846-91053846;hs4:91461399-91461399,hs4:91691354-91691354;hs4:91979400-91979400,hs4:92224971-92224971;hs4:118134983-118134983,hs22:29069747-29069747;hs5:14306599-14306599,hs5:14306502-14306502;hs5:34190759-34190759,hs5:34192112-34192112;hs5:37161164-37161164,hs5:37163562-37163562;hs5:40616807-40616807,hs9:72756717-72756717;hs5:40963576-40963576,hs5:40964800-40964800;hs5:41052889-41052889,hs5:41059276-41059276;hs5:41595687-41595687,hs5:41596910-41596910;hs5:50421331-50421331,hs5:166187434-166187434;hs5:50421331-50421331,hs6:83384948-83384948;hs5:114072107-114072107,hs5:114072873-114072873;hs5:128839852-128839852,hs5:128840448-128840448;hs5:155637754-155637754,hs5:155641421-155641421;hs5:157250953-157250953,hs5:157250849-157250849;hs5:166187431-166187431,hs6:83384969-83384969;hs5:168860676-168860676,hs5:168860735-168860735;hs5:174234425-174234425,hs5:174292349-174292349;hs6:1864425-1864425,hs6:2152667-2152667;hs6:47437070-47437070,hs6:47436991-47436991;hs6:57157681-57157681,hs6:57132337-57132337;hs6:100977746-100977746,hs6:101013523-101013523;hs6:136579181-136579181,hs6:137020805-137020805;hs6:145139866-145139866,hs6:145140072-145140072;hs6:147889630-147889630,hs6:147893169-147893169;hs6:148153858-148153858,hs6:148208095-148208095;hs6:162054192-162054192,hs6:162060381-162060381;hs6:162059550-162059550,hs6:162060424-162060424;hs7:58048681-58048681,hs7:58047811-58047811;hs7:76009276-76009276,hs7:93089880-93089880;hs7:90158660-90158660,hs7:90159528-90159528;hs7:90216578-90216578,hs7:90845876-90845876;hs7:92920951-92920951,hs7:92921189-92921189;hs7:93047980-93047980,hs7:93048677-93048677;hs7:93287774-93287774,hs7:93290165-93290165;hs7:110929929-110929929,hs7:111041257-111041257;hs8:34304245-34304245,hs8:34314423-34314423;hs8:37750566-37750566,hs8:37752421-37752421;hs8:38988892-38988892,hs15:49219495-49219495;hs8:38988966-38988966,hs15:49219381-49219381;hs8:39001990-39001990,hs10:103483009-103483009;hs8:39440892-39440892,hs8:38993109-38993109;hs8:39562004-39562004,hs15:49453994-49453994;hs8:40117904-40117904,hs11:130120591-130120591;hs8:42107804-42107804,hs15:39005422-39005422;hs8:43284965-43284965,hs8:43269133-43269133;hs8:49300180-49300180,hs8:49289677-49289677;hs8:70661732-70661732,hs8:70662051-70662051;hs8:89569077-89569077,hs8:89646163-89646163;hs8:99344109-99344109,hs10:13349481-13349481;hs8:132007762-132007762,hs8:132008837-132008837;hs8:139240256-139240256,hs8:139334770-139334770;hs9:9420818-9420818,hs9:9613033-9613033;hs9:9757459-9757459,hs9:9759733-9759733;hs9:24689262-24689262,hs9:24691606-24691606;hs9:26533795-26533795,hs20:36768977-36768977;hs9:27085342-27085342,hs11:132513276-132513276;hs9:41251640-41251640,hs9:41252642-41252642;hs9:72757009-72757009,hs5:40615479-40615479;hs9:115559851-115559851,hs13:68353129-68353129;hs9:125028422-125028422,hs9:125028363-125028363;hs10:65032304-65032304,hs10:65258680-65258680;hs10:68269039-68269039,hs10:68269138-68269138;hs10:73735935-73735935,hs11:111182037-111182037;hs10:73846718-73846718,hs10:73857371-73857371;hs10:77152236-77152236,hs10:77108846-77108846;hs10:77285867-77285867,hs10:77487657-77487657;hs10:103581820-103581820,hs10:73845866-73845866;hs10:114635050-114635050,hs10:114634937-114634937;hs11:60746447-60746447,hs11:65121030-65121030;hs11:70542011-70542011,hs11:69038492-69038492;hs11:77797644-77797644,hs11:77785249-77785249;hs11:78324104-78324104,hs11:78299900-78299900;hs11:87858003-87858003,hs11:78322458-78322458;hs11:89180783-89180783,hs11:89183306-89183306;hs11:89183199-89183199,hs11:95254202-95254202;hs11:90527374-90527374,hs11:76987312-76987312;hs11:91056798-91056798,hs11:91056934-91056934;hs11:91819379-91819379,hs11:125197948-125197948;hs11:96743626-96743626,hs15:90256776-90256776;hs11:111163141-111163141,hs17:46727898-46727898;hs11:111224559-111224559,hs15:59283036-59283036;hs11:111701014-111701014,hs11:127303158-127303158;hs11:111701146-111701146,hs11:111709642-111709642;hs11:114864722-114864722,hs11:130711965-130711965;hs11:119717398-119717398,hs11:124347783-124347783;hs11:124331422-124331422,hs11:124347445-124347445;hs11:124672255-124672255,hs11:125891376-125891376;hs11:126620593-126620593,hs15:31651506-31651506;hs11:129585663-129585663,hs15:58314001-58314001;hs11:129976029-129976029,hs8:38988362-38988362;hs11:131033208-131033208,hs11:131037530-131037530;hs12:8413856-8413856,hs12:8414197-8414197;hs12:111962174-111962174,hs12:111962120-111962120;hs12:120740047-120740047,hs12:120701792-120701792;hs13:20859229-20859229,hs13:21256185-21256185;hs13:20922876-20922876,hs13:34084293-34084293;hs13:21116366-21116366,hs13:21118163-21118163;hs13:21137172-21137172,hs13:21139835-21139835;hs13:33337087-33337087,hs13:33339402-33339402;hs13:33557069-33557069,hs13:33558367-33558367;hs13:33563029-33563029,hs13:42268576-42268576;hs13:33573621-33573621,hs13:43329134-43329134;hs13:33595014-33595014,hs13:33597473-33597473;hs13:33769483-33769483,hs13:33769391-33769391;hs13:34018710-34018710,hs13:35020737-35020737;hs13:34226509-34226509,hs13:34229150-34229150;hs13:34478084-34478084,hs13:34479606-34479606;hs13:34492260-34492260,hs13:39455275-39455275;hs13:35086092-35086092,hs13:37898738-37898738;hs13:38402936-38402936,hs13:43077549-43077549;hs13:38557873-38557873,hs13:38563695-38563695;hs13:38606089-38606089,hs13:38612401-38612401;hs13:38608855-38608855,hs13:40313169-40313169;hs13:38632985-38632985,hs13:38625896-38625896;hs13:38646601-38646601,hs13:38648855-38648855;hs13:40314079-40314079,hs13:33392243-33392243;hs13:41243877-41243877,hs13:41445700-41445700;hs13:42156082-42156082,hs13:34058258-34058258;hs13:43959721-43959721,hs13:34671620-34671620;hs13:44792246-44792246,hs13:44794287-44794287;hs13:75599322-75599322,hs18:40237990-40237990;hs14:20602682-20602682,hs19:58412492-58412492;hs14:50422546-50422546,hs14:50422459-50422459;hs14:85452604-85452604,hs14:85454751-85454751;hs15:31651667-31651667,hs8:37636133-37636133;hs15:33388345-33388345,hs15:33396908-33396908;hs15:34120129-34120129,hs11:91818434-91818434;hs15:39160173-39160173,hs18:78016996-78016996;hs15:45040475-45040475,hs15:39154443-39154443;hs15:53118166-53118166,hs15:53117894-53117894;hs15:53120356-53120356,hs15:71121478-71121478;hs15:53120806-53120806,hs15:71116589-71116589;hs15:53121079-53121079,hs15:53124001-53124001;hs15:57832682-57832682,hs15:57832810-57832810;hs15:58555519-58555519,hs15:58556747-58556747;hs15:58643567-58643567,hs15:73498474-73498474;hs15:60262065-60262065,hs15:38909215-38909215;hs15:62284286-62284286,hs15:62395244-62395244;hs15:69364988-69364988,hs14:47814685-47814685;hs15:76765317-76765317,hs15:76977425-76977425;hs16:24575787-24575787,hs16:24575564-24575564;hs16:78182406-78182406,hs16:78292779-78292779;hs16:78569413-78569413,hs16:78737455-78737455;hs16:78899343-78899343,hs16:79058395-79058395;hs17:14071429-14071429,hs17:31028654-31028654;hs17:30984003-30984003,hs17:33576587-33576587;hs17:31230668-31230668,hs17:31230610-31230610;hs17:37530061-37530061,hs17:37531315-37531315;hs17:37614537-37614537,hs17:37633305-37633305;hs17:37669074-37669074,hs17:37687745-37687745;hs17:37678445-37678445,hs17:37686261-37686261;hs17:37743549-37743549,hs17:37671984-37671984;hs17:37795276-37795276,hs17:37820792-37820792;hs17:37809409-37809409,hs17:37815116-37815116;hs17:37955856-37955856,hs17:37956135-37956135;hs17:38004834-38004834,hs2:4530411-4530411;hs17:38050793-38050793,hs17:38054476-38054476;hs17:53232767-53232767,hs17:53236111-53236111;hs17:53245400-53245400,hs17:53283533-53283533;hs17:56406981-56406981,hs17:56452005-56452005;hs18:6436154-6436154,hs18:6720421-6720421;hs18:18792159-18792159,hsX:99121818-99121818;hs18:19339002-19339002,hs18:19338898-19338898;hs18:19932891-19932891,hs18:19946342-19946342;hs18:19936955-19936955,hs18:19940506-19940506;hs18:20427303-20427303,hs19:22595623-22595623;hs18:20984227-20984227,hs14:34199316-34199316;hs19:43167386-43167386,hs19:43167859-43167859;hs19:45379198-45379198,hs19:53426410-53426410;hs19:47742400-47742400,hs19:47912472-47912472;hs19:49012196-49012196,hs19:49016780-49016780;hs19:58373478-58373478,hs19:58376344-58376344;hs19:59065210-59065210,hs19:59066830-59066830;hs20:12168914-12168914,hs20:12182170-12182170;hs20:14672098-14672098,hs20:15157704-15157704;hs20:14739729-14739729,hs20:14840096-14840096;hs20:14861770-14861770,hs20:14950224-14950224;hs20:15024930-15024930,hs20:15076470-15076470;hs20:15087208-15087208,hs20:15157992-15157992;hs20:36575690-36575690,hs20:36586855-36586855;hs20:36586987-36586987,hs20:36587107-36587107;hs22:22740293-22740293,hs22:22743276-22743276;hs22:22785126-22785126,hs7:72379850-72379850;hsX:7043348-7043348,hsX:7043627-7043627;hsX:7262713-7262713,hsX:7397451-7397451;hsX:8074686-8074686,hsX:8167174-8167174;hsX:10382704-10382704,hsX:104048435-104048435;hsX:16784595-16784595,hsX:16612152-16612152;hsX:16967888-16967888,hsX:88160053-88160053;hsX:20395762-20395762,hsX:77072893-77072893;hsX:22457784-22457784,hsX:54666169-54666169;hsX:22750290-22750290,hsX:121042778-121042778;hsX:22774834-22774834,hsX:82337743-82337743;hsX:26730892-26730892,hsX:26705602-26705602;hsX:26845859-26845859,hsX:54666841-54666841;hsX:29622708-29622708,hsX:39752637-39752637;hsX:30776239-30776239,hsX:50843336-50843336;hsX:36778830-36778830,hsX:50344239-50344239;hsX:36779071-36779071,hsX:43935302-43935302;hsX:37208058-37208058,hsX:37208594-37208594;hsX:39854540-39854540,hsX:40053753-40053753;hsX:40073270-40073270,hsX:43717860-43717860;hsX:40604906-40604906,hsX:103354883-103354883;hsX:40607695-40607695,hsX:40195849-40195849;hsX:40834670-40834670,hsX:32873592-32873592;hsX:41815689-41815689,hsX:88161258-88161258;hsX:43220056-43220056,hsX:96291198-96291198;hsX:43249883-43249883,hsX:140336250-140336250;hsX:45313626-45313626,hsX:45314370-45314370;hsX:45772558-45772558,hsX:46398445-46398445;hsX:47644686-47644686,hsX:47573038-47573038;hsX:49134065-49134065,hsX:76808537-76808537;hsX:53122342-53122342,hsX:16968073-16968073;hsX:53122593-53122593,hsX:76809436-76809436;hsX:69093276-69093276,hsX:69077231-69077231;hsX:74169945-74169945,hsX:74171592-74171592;hsX:77086454-77086454,hsX:121057115-121057115;hsX:78286734-78286734,hsX:78275738-78275738;hsX:80088147-80088147,hsX:80067834-80067834;hsX:81091183-81091183,hsX:71723404-71723404;hsX:88415683-88415683,hsX:34125264-34125264;hsX:96313911-96313911,hsX:99058092-99058092;hsX:100621381-100621381,hsX:39838545-39838545;hsX:101799507-101799507,hsX:44920070-44920070;hsX:103349055-103349055,hs3:84873687-84873687;hsX:104425105-104425105,hsX:104425483-104425483;hsX:107008221-107008221,hsX:68823769-68823769;hsX:107010117-107010117,hsX:134141066-134141066;hsX:120321716-120321716,hsX:120343409-120343409;hsX:122724821-122724821,hsX:122725519-122725519;hsX:131032627-131032627,hsX:131039417-131039417;hsX:138273593-138273593,hsX:139041700-139041700;hsX:138273914-138273914,hsX:139042364-139042364;hsX:139622193-139622193,hsX:140515830-140515830 FHIT;MACROD2;FAM190A;WWOX;CDK12;CDK14;ADAM32;PTPRD;PARK2;ALDH1A2;IKZF3;IL1RAPL2;NOX4;ALG9;RFC3;STARD3;ZNF587;IMMP2L;SMYD3;CTNNA3;GMDS;SCAPER;DIAPH2;KIF26B;HDHD1;SAMD5;UTRN;ASCC3;VWA8;FNDC3B;C10orf11;SGCD;TMEM39B;C7;CLINT1;C5orf42;STXBP4;SLCO5A1;CGNL1;MAMDC2;FMN1;GNGT1;TRIO;FAM135B;FGF13;KCNAB1;C1orf168;SYCP1;SPOCK2;ATXN2;PDS5B;KL;STARD13;COG6;KLF13;SHC4;RBBP6;MYO1D;FBXL20;MIB1;CTD-2583A14.10;ZNF587B;ZNF814;MYO1B;RFT1;IFT80;HEATR7B2;ADAMTS19;CCDC132;RAB11FIP1;ADCY8;MRRF;REPS2;EDA;ATRX;SLC25A53;TSC22D3;CXorf66;TTC28;DMD;ROBO2;CADM2;SNX30;TMEM241;MDGA2;BCLAF1;STS;ASCC1;RNF43;KDM6A;SHANK2;OPCML;ERBB4;IL1RAPL1;NPAS3;ZBTB8A;ADAM18;POU2AF1;PIKFYVE;RBBP8;NOTCH2;RNF111;FREM2;NEO1;ENOX1;DPYD;JMJD1C;CHST3;CD6;GDPD4;NDUFC2-KCTD14;NDUFC2;RAB38;PKNOX2;CDON;KIRREL3;APLP2;ZBTB44;PXN;SETD8;IFT88;TRPC4;RYR3;TRIM69;GALK2;VPS13C;WDR93;COX10;SLFN5;TCAP;ZNF98;PVRL2;MEIS3;LMTK3;ZNF805;ZNF417;CHMP2A;SLC39A10;MOB4;TGM2;CIDEC;IL17RE;GADL1;MAP3K5;POM121;CALCR;PROSC;CTPS2;PRRG1;TM4SF2;MAOB;ZNF674;PPP1R3F;SHROOM4;HDAC8;MAGT1;BTK;SPANXC Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes PPP1R3F,ATRX CTDB0189 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 6 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_1430 Illumina HiSeq 2000 hs1:45187575-45187575,hs20:32340371-32340371;hs1:45713766-45713766,hs7:22840546-22840546;hs1:53305646-53305646,hs10:9474847-9474847;hs1:67666735-67666735,hs1:67666889-67666889;hs1:93514448-93514448,hs1:91561231-91561231;hs1:179835690-179835690,hs1:179843552-179843552;hs1:199801600-199801600,hs1:206519062-206519062;hs1:202069042-202069042,hs1:206483841-206483841;hs1:202073323-202073323,hs1:212934209-212934209;hs1:202073453-202073453,hs1:210882821-210882821;hs1:204165732-204165732,hs8:11851918-11851918;hs1:204171636-204171636,hs1:202835671-202835671;hs1:209399338-209399338,hs8:11848018-11848018;hs1:210883531-210883531,hs1:204171456-204171456;hs1:237672255-237672255,hs18:29071133-29071133;hs1:239657098-239657098,hs1:239657269-239657269;hs2:76173805-76173805,hs2:76173911-76173911;hs2:95512700-95512700,hs8:225645-225645;hs2:131425859-131425859,hs2:131422699-131422699;hs2:161418611-161418611,hs7:85549613-85549613;hs2:161427144-161427144,hs2:161438200-161438200;hs2:185158658-185158658,hs2:185151023-185151023;hs2:206264093-206264093,hs2:206395957-206395957;hs2:215828726-215828726,hs22:29066028-29066028;hs3:4323823-4323823,hs3:4325884-4325884;hs3:60376005-60376005,hs3:60397769-60397769;hs3:60470207-60470207,hs3:60605378-60605378;hs3:60479633-60479633,hs3:60600610-60600610;hs3:60837576-60837576,hs3:60872302-60872302;hs3:112561869-112561869,hs8:11099111-11099111;hs3:145779230-145779230,hs13:33131040-33131040;hs3:178175102-178175102,hs4:121161177-121161177;hs4:121161069-121161069,hs6:142258188-142258188;hs4:131652335-131652335,hs4:131520440-131520440;hs4:154219439-154219439,hs4:154219516-154219516;hs5:17049753-17049753,hs5:17051000-17051000;hs5:17049982-17049982,hs5:17051025-17051025;hs5:116579609-116579609,hs5:116579743-116579743;hs5:135103838-135103838,hs5:135103921-135103921;hs5:170825481-170825481,hs5:170825341-170825341;hs6:11259891-11259891,hs6:11276889-11276889;hs6:11259922-11259922,hs6:11260066-11260066;hs6:11260329-11260329,hs6:11260732-11260732;hs6:11360754-11360754,hs6:17294417-17294417;hs6:11419306-11419306,hs6:11552019-11552019;hs6:11552187-11552187,hs6:11275818-11275818;hs6:11661311-11661311,hs6:16255096-16255096;hs6:11679014-11679014,hs6:11260303-11260303;hs6:17554049-17554049,hs6:19592156-19592156;hs6:17609360-17609360,hs6:17611022-17611022;hs6:18437137-18437137,hs6:19764793-19764793;hs6:18437826-18437826,hs6:19583260-19583260;hs6:18728548-18728548,hs6:19408356-19408356;hs6:19915091-19915091,hs6:19915169-19915169;hs6:22034828-22034828,hs6:23182587-23182587;hs6:22433848-22433848,hs6:22436561-22436561;hs6:23182601-23182601,hs15:31613192-31613192;hs6:23447191-23447191,hs11:86012564-86012564;hs6:26865214-26865214,hs6:26866815-26866815;hs6:28813931-28813931,hs6:28050944-28050944;hs6:30152615-30152615,hs6:30679417-30679417;hs6:31422300-31422300,hs14:77288042-77288042;hs6:31427863-31427863,hs17:63590248-63590248;hs6:39342307-39342307,hs6:39346045-39346045;hs6:52867368-52867368,hs6:52869497-52869497;hs6:70277235-70277235,hs10:8404673-8404673;hs6:86318444-86318444,hs6:86318718-86318718;hs7:51215217-51215217,hs7:51218250-51218250;hs7:53439489-53439489,hs7:53440366-53440366;hs7:53610217-53610217,hs7:53614716-53614716;hs7:53853438-53853438,hs7:55384887-55384887;hs7:54435504-54435504,hs7:54438304-54438304;hs7:54553465-54553465,hs17:26051045-26051045;hs7:55194619-55194619,hs7:55196042-55196042;hs7:55317234-55317234,hs7:55221067-55221067;hs7:55593068-55593068,hs7:55596507-55596507;hs7:61848994-61848994,hs16:32503564-32503564;hs7:61985927-61985927,hs7:61986590-61986590;hs7:62037696-62037696,hs7:62038642-62038642;hs7:83949165-83949165,hs7:83951519-83951519;hs7:87001471-87001471,hs7:87007644-87007644;hs7:93558172-93558172,hs7:93560787-93560787;hs7:97707334-97707334,hs7:97708912-97708912;hs7:110652072-110652072,hs7:110652232-110652232;hs7:157865712-157865712,hs7:157867484-157867484;hs7:157956573-157956573,hs7:157956357-157956357;hs8:1099990-1099990,hs8:11289576-11289576;hs8:1258963-1258963,hs8:39771895-39771895;hs8:2276084-2276084,hs8:11393487-11393487;hs8:2276427-2276427,hs8:6506739-6506739;hs8:6507042-6507042,hs8:41613670-41613670;hs8:6666907-6666907,hs9:72326782-72326782;hs8:7004762-7004762,hs8:7005654-7005654;hs8:7004979-7004979,hs8:5805459-5805459;hs8:7920620-7920620,hs9:75500171-75500171;hs8:10350716-10350716,hs8:41524365-41524365;hs8:10571499-10571499,hs9:75499868-75499868;hs8:10738956-10738956,hs8:42392331-42392331;hs8:10791274-10791274,hs9:74861823-74861823;hs8:10826992-10826992,hs8:12019557-12019557;hs8:11094158-11094158,hs8:11618317-11618317;hs8:11098945-11098945,hs18:22222521-22222521;hs8:11098945-11098945,hs3:112561767-112561767;hs8:11102161-11102161,hs8:42199598-42199598;hs8:11102286-11102286,hs8:11101667-11101667;hs8:11226763-11226763,hs8:10613306-10613306;hs8:11248591-11248591,hs8:41598780-41598780;hs8:11278051-11278051,hs9:73849518-73849518;hs8:11278409-11278409,hs8:11225919-11225919;hs8:11292180-11292180,hs8:42166123-42166123;hs8:11299448-11299448,hs8:11443516-11443516;hs8:11316337-11316337,hs9:71797987-71797987;hs8:11316501-11316501,hs8:11374595-11374595;hs8:11327907-11327907,hs8:42132546-42132546;hs8:11375499-11375499,hs8:11278502-11278502;hs8:11394058-11394058,hs8:41731500-41731500;hs8:11422998-11422998,hs8:42352825-42352825;hs8:11425287-11425287,hs9:71798531-71798531;hs8:11492949-11492949,hs9:72208904-72208904;hs8:11600799-11600799,hs8:41567543-41567543;hs8:11608835-11608835,hs8:12185832-12185832;hs8:11638417-11638417,hs9:72209830-72209830;hs8:11659117-11659117,hs9:71684008-71684008;hs8:11669610-11669610,hs9:72174671-72174671;hs8:11670029-11670029,hs8:10592639-10592639;hs8:11705595-11705595,hs8:42007850-42007850;hs8:11708966-11708966,hs8:11091788-11091788;hs8:11784232-11784232,hs8:42283502-42283502;hs8:11811699-11811699,hs9:72069938-72069938;hs8:11847837-11847837,hs1:206525115-206525115;hs8:11890126-11890126,hs8:11783805-11783805;hs8:11983042-11983042,hs8:10826580-10826580;hs8:12186081-12186081,hs9:75655507-75655507;hs8:12461472-12461472,hs8:42481557-42481557;hs8:14541578-14541578,hs22:29066034-29066034;hs8:39773189-39773189,hs8:1817126-1817126;hs8:41614038-41614038,hs9:75340977-75340977;hs8:41621110-41621110,hs9:72345710-72345710;hs8:41624027-41624027,hs8:6666442-6666442;hs8:41709172-41709172,hs8:42128692-42128692;hs8:41885046-41885046,hs8:42480907-42480907;hs8:41885408-41885408,hs8:41708786-41708786;hs8:41908907-41908907,hs8:41913702-41913702;hs8:41921423-41921423,hs9:75474354-75474354;hs8:42008230-42008230,hs8:42163391-42163391;hs8:42064600-42064600,hs8:42068302-42068302;hs8:42129111-42129111,hs9:72210295-72210295;hs8:42199314-42199314,hs8:42341936-42341936;hs8:42280210-42280210,hs9:75316100-75316100;hs8:42342855-42342855,hs8:41598414-41598414;hs8:42353180-42353180,hs8:42554102-42554102;hs8:42378642-42378642,hs8:42761360-42761360;hs8:42379098-42379098,hs8:11608416-11608416;hs8:42398111-42398111,hs9:72345292-72345292;hs8:42431647-42431647,hs8:10764950-10764950;hs8:42593185-42593185,hs9:71518479-71518479;hs8:42761856-42761856,hs8:11247416-11247416;hs8:42826117-42826117,hs9:75654679-75654679;hs8:42826506-42826506,hs9:79293084-79293084;hs8:97764748-97764748,hs8:100269275-100269275;hs8:104804382-104804382,hs8:138803774-138803774;hs8:108515202-108515202,hs8:104801993-104801993;hs8:138804851-138804851,hs20:53460328-53460328;hs8:145245140-145245140,hs19:21777931-21777931;hs9:71180894-71180894,hs9:71847565-71847565;hs9:71519038-71519038,hs8:42431034-42431034;hs9:71852834-71852834,hs8:7255749-7255749;hs9:72069486-72069486,hs9:75340655-75340655;hs9:72176367-72176367,hs9:75318656-75318656;hs9:72210683-72210683,hs8:11315943-11315943;hs9:74862452-74862452,hs8:11753787-11753787;hs9:75027623-75027623,hs8:6526495-6526495;hs9:75475294-75475294,hs8:11654268-11654268;hs9:79621309-79621309,hs20:15771658-15771658;hs9:93939219-93939219,hs9:93939721-93939721;hs9:111804499-111804499,hs9:111886223-111886223;hs9:123170135-123170135,hs7:64020959-64020959;hs10:20168028-20168028,hs10:20168149-20168149;hs10:97329238-97329238,hs10:97519635-97519635;hs10:119737160-119737160,hs10:119943392-119943392;hs11:51478350-51478350,hs11:51479949-51479949;hs11:55108356-55108356,hs11:55108426-55108426;hs11:55512525-55512525,hs11:55512724-55512724;hs11:63671092-63671092,hs11:63646445-63646445;hs11:72595463-72595463,hs11:72598652-72598652;hs11:74753517-74753517,hs11:74755387-74755387;hs11:74754089-74754089,hs11:74755399-74755399;hs11:74919246-74919246,hs11:74925496-74925496;hs11:75179851-75179851,hs11:77191238-77191238;hs11:77203164-77203164,hs11:77205650-77205650;hs11:77860111-77860111,hs11:77880042-77880042;hs11:78071980-78071980,hs11:78185574-78185574;hs11:78204585-78204585,hs11:78209925-78209925;hs11:78271871-78271871,hs11:78314855-78314855;hs11:78375287-78375287,hs11:78381612-78381612;hs11:85481223-85481223,hs11:104166676-104166676;hs11:93161896-93161896,hsX:85804744-85804744;hs11:107465699-107465699,hs11:107396063-107396063;hs11:131806081-131806081,hs11:131808699-131808699;hs12:64521010-64521010,hs12:64524568-64524568;hs12:64524383-64524383,hs12:64524578-64524578;hs12:130693334-130693334,hs12:130517202-130517202;hs13:27034802-27034802,hs13:27049746-27049746;hs13:33130429-33130429,hs3:145763283-145763283;hs13:83906684-83906684,hs22:29065749-29065749;hs14:25360580-25360580,hs14:25232521-25232521;hs14:43652728-43652728,hs14:43653341-43653341;hs14:73726262-73726262,hs14:73793963-73793963;hs14:89515255-89515255,hs14:89516739-89516739;hs14:102901214-102901214,hs14:102874328-102874328;hs15:20618442-20618442,hs10:42637229-42637229;hs15:33294651-33294651,hs15:33294331-33294331;hs15:41865665-41865665,hs15:41865876-41865876;hs15:42344464-42344464,hs15:42347527-42347527;hs15:77039629-77039629,hs15:77152560-77152560;hs15:94039521-94039521,hs15:94041192-94041192;hs15:97417100-97417100,hs1:223199842-223199842;hs16:78716494-78716494,hs16:78719392-78719392;hs16:78746861-78746861,hs16:78770995-78770995;hs17:28008681-28008681,hs17:28021838-28021838;hs17:28039974-28039974,hs17:28042584-28042584;hs17:28108620-28108620,hs7:64522155-64522155;hs17:28593778-28593778,hs17:28598195-28598195;hs18:2617662-2617662,hs18:2530574-2530574;hs18:12039471-12039471,hs18:19000252-19000252;hs18:12040275-12040275,hs18:29091910-29091910;hs18:12053065-12053065,hs18:18989549-18989549;hs18:12053157-12053157,hs18:18996901-18996901;hs18:12054693-12054693,hs18:18990219-18990219;hs18:12054699-12054699,hs18:18990219-18990219;hs18:12054699-12054699,hs18:18990219-18990219;hs18:14184199-14184199,hs18:14184304-14184304;hs18:18990433-18990433,hs18:48543544-48543544;hs18:18991090-18991090,hs18:29071397-29071397;hs18:18997357-18997357,hs18:12039790-12039790;hs18:18997566-18997566,hs18:29956086-29956086;hs18:18997843-18997843,hs18:38088954-38088954;hs18:21531348-21531348,hs18:27742129-27742129;hs18:23867609-23867609,hs18:48543843-48543843;hs18:23867816-23867816,hs18:48543855-48543855;hs18:29094206-29094206,hs18:29104650-29104650;hs18:33927218-33927218,hs18:33790255-33790255;hs18:48557544-48557544,hs18:23867816-23867816;hs18:48557662-48557662,hs18:12052078-12052078;hs19:14964341-14964341,hs22:29065821-29065821;hs19:15217405-15217405,hs19:15220193-15220193;hs19:20207724-20207724,hs19:20209804-20209804;hs19:43449296-43449296,hs19:43781608-43781608;hs20:3748448-3748448,hs20:3748576-3748576;hs20:14466308-14466308,hs20:14466373-14466373;hs20:25733206-25733206,hs20:25666620-25666620;hs20:25920696-25920696,hs12:37890328-37890328;hs20:30961449-30961449,hs20:30885347-30885347;hs20:58901856-58901856,hs20:58915693-58915693;hs20:58901871-58901871,hs20:59374517-59374517;hs20:59022127-59022127,hs22:29065226-29065226;hs21:16154804-16154804,hs21:19658087-19658087;hs21:16391511-16391511,hs21:25773517-25773517;hs21:32234009-32234009,hs21:32234616-32234616;hs21:33279078-33279078,hs21:33910456-33910456;hs21:33382953-33382953,hs21:33423317-33423317;hs21:36197079-36197079,hs21:36431084-36431084;hs21:36435710-36435710,hs21:36436638-36436638;hs22:29065590-29065590,hs22:29065779-29065779;hs22:29065749-29065749,hs13:83906684-83906684;hs22:29066119-29066119,hs19:14964334-14964334;hsX:28254672-28254672,hsX:28255182-28255182;hsX:80830788-80830788,hsX:80830947-80830947;hsX:96797085-96797085,hsX:96820404-96820404;hsX:130813254-130813254,hsX:130974300-130974300;hsX:145124623-145124623,hsX:145135122-145135122 GREB1L;ANK1;TTC28;NEDD9;C8orf12;SLC20A2;FHIT;APBA1;FAM167A;SMAD4;SSH2;WWOX;PTPRN2;XKR6;FDFT1;IKBKB;SRGAP1;EGFR;NARS2;BLK;HOOK3;TJP2;TMC1;MACROD2;GATA4;KAT6A;TAF4B;DSG2;PTAR1;IMMP2L;PARD3B;SUMF1;SCAPER;DIAPH2;PIP5K1B;ALDH1A1;KIF6;PLXDC2;TENM4;RIMS2;NPM1;POLB;BLMH;ICK;IL23R;SOX7;SOX7;RNF144B;SRGAP2;TECPR2;FCHSD2;TRIM2;SEMA3A;FMN1;NTM;TOR1AIP2;GOLT1A;KCNH1;MARK2;ZNF90;C20orf27;HUNK;CD200R1L;TMEM170B;FAM8A1;SYNCRIP;COBL;VOPP1;CROT;CTSB;IDO1;GDA;LAMA3;RUNX1;VPS13B;CCDC67;CDK5RAP2;GAB2;HEATR7A;TRPM3;KCNMB2;RYR2;KIF3B;PLAT;CHRNB3;ARHGEF10;ASXL1;NRIP1;PRUNE2;FHOD3;SGCZ;C1orf228;NSL1;ENTPD1;GDPD5;SYTL2;ALKBH8;ELMOD1;STXBP6;PAPLN;NUMB;FAM59A;MOCOS;SYDE1;ABCA12;ZNF337;ZNF341;TMPRSS15;GMPR;CAP2;ZNF165;TRIM26;MDC1;ZNF680;NEIL2;DEFB134;C8orf40;CPQ;FXN;TMEM245;DACH2 Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes TRIM26,MDC1 CTDB0190 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 9 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_1527 Illumina HiSeq 2000 hs1:14815932-14815932,hs1:15279324-15279324;hs1:84518094-84518094,hs2:72559973-72559973;hs1:94557656-94557656,hs1:95030924-95030924;hs1:148928328-148928328,hs2:91848054-91848054;hs2:11220260-11220260,hs12:70285490-70285490;hs2:36567772-36567772,hs2:144565145-144565145;hs2:36567781-36567781,hs2:36568063-36568063;hs2:55400986-55400986,hs2:188649956-188649956;hs2:133459272-133459272,hs2:133460396-133460396;hs2:134187405-134187405,hs2:134233446-134233446;hs2:154637041-154637041,hs12:27352539-27352539;hs2:154637226-154637226,hs12:26616002-26616002;hs2:160149189-160149189,hs17:32859605-32859605;hs2:181868467-181868467,hs2:181868548-181868548;hs2:185469657-185469657,hs2:185471526-185471526;hs3:19686994-19686994,hs3:45012058-45012058;hs3:44884661-44884661,hs3:132849902-132849902;hs3:60117508-60117508,hs3:60213309-60213309;hs3:60312792-60312792,hs3:60463221-60463221;hs3:60321022-60321022,hs3:60475090-60475090;hs3:60489902-60489902,hs3:60561145-60561145;hs3:78036982-78036982,hs12:30186017-30186017;hs3:131265559-131265559,hs3:131267973-131267973;hs3:132725456-132725456,hs3:19919903-19919903;hs4:121671864-121671864,hs21:43328371-43328371;hs4:137647748-137647748,hs6:13191274-13191274;hs5:20728063-20728063,hs5:20728246-20728246;hs5:28692759-28692759,hs5:28716107-28716107;hs5:81709331-81709331,hs5:81869806-81869806;hs6:909992-909992,hs6:909680-909680;hs6:13191179-13191179,hs6:19552312-19552312;hs6:79452855-79452855,hs6:79453181-79453181;hs6:111627656-111627656,hs9:27894135-27894135;hs6:111627906-111627906,hs9:27894850-27894850;hs6:147082917-147082917,hs6:13191277-13191277;hs6:162881053-162881053,hs6:163169356-163169356;hs7:14549342-14549342,hs7:14553234-14553234;hs7:43792510-43792510,hs7:43715048-43715048;hs7:55515221-55515221,hs7:55519802-55519802;hs7:102479154-102479154,hs7:102647535-102647535;hs8:21348247-21348247,hs8:38580230-38580230;hs8:30068001-30068001,hs8:30070627-30070627;hs8:36033789-36033789,hs8:90361210-90361210;hs8:36036067-36036067,hs8:36039121-36039121;hs8:38468414-38468414,hs13:25473722-25473722;hs8:127770177-127770177,hs8:129295656-129295656;hs8:127835272-127835272,hs8:129291463-129291463;hs8:127835343-127835343,hs10:122929007-122929007;hs8:127840493-127840493,hs8:129557677-129557677;hs8:127910603-127910603,hs10:122699911-122699911;hs8:127910999-127910999,hs10:122973397-122973397;hs8:128049168-128049168,hs8:128530580-128530580;hs8:128049290-128049290,hs8:129574034-129574034;hs8:128057423-128057423,hs8:128648393-128648393;hs8:128062704-128062704,hs8:128653093-128653093;hs8:128091386-128091386,hs8:128716554-128716554;hs8:128098720-128098720,hs8:129606301-129606301;hs8:128253770-128253770,hs8:129600700-129600700;hs8:128254407-128254407,hs8:128737967-128737967;hs8:128261067-128261067,hs8:129704272-129704272;hs8:128268748-128268748,hs8:129602962-129602962;hs8:128457328-128457328,hs8:128530784-128530784;hs8:128583356-128583356,hs8:128651307-128651307;hs8:128680357-128680357,hs8:128518778-128518778;hs8:128686157-128686157,hs8:128560607-128560607;hs8:128794903-128794903,hs10:122960199-122960199;hs8:129291464-129291464,hs10:122929008-122929008;hs8:129739860-129739860,hs8:127740855-127740855;hs9:5567421-5567421,hs9:4471045-4471045;hs9:5585307-5585307,hs9:4962651-4962651;hs9:6017773-6017773,hs9:22712995-22712995;hs9:6049094-6049094,hs9:107510295-107510295;hs9:6742311-6742311,hs9:129977689-129977689;hs9:7036512-7036512,hs9:125990253-125990253;hs9:7088434-7088434,hs9:78462736-78462736;hs9:7342899-7342899,hs9:89181699-89181699;hs9:7693355-7693355,hs9:103970580-103970580;hs9:9845711-9845711,hs9:76596915-76596915;hs9:10155874-10155874,hs9:73115250-73115250;hs9:11952993-11952993,hs9:12112100-12112100;hs9:11953396-11953396,hs9:105606604-105606604;hs9:12479163-12479163,hs9:97311724-97311724;hs9:12873108-12873108,hs9:112756911-112756911;hs9:13070763-13070763,hs9:112584448-112584448;hs9:15202384-15202384,hs9:135521271-135521271;hs9:15577294-15577294,hs9:94427114-94427114;hs9:17770514-17770514,hs9:24125486-24125486;hs9:18930469-18930469,hs9:111503009-111503009;hs9:19588487-19588487,hs9:88831696-88831696;hs9:20044444-20044444,hs9:21469247-21469247;hs9:21550386-21550386,hs9:19591824-19591824;hs9:22170983-22170983,hs9:105713839-105713839;hs9:24019025-24019025,hs9:97321657-97321657;hs9:24699197-24699197,hs9:94298177-94298177;hs9:25080520-25080520,hs9:25670817-25670817;hs9:25885035-25885035,hs9:121717914-121717914;hs9:25915996-25915996,hs9:134650973-134650973;hs9:27814176-27814176,hs9:94491647-94491647;hs9:28074052-28074052,hs9:91251679-91251679;hs9:29265771-29265771,hs9:36951369-36951369;hs9:29268327-29268327,hs15:98633601-98633601;hs9:32322003-32322003,hs9:21984033-21984033;hs9:33519538-33519538,hs9:17733694-17733694;hs9:33520209-33520209,hs9:94381287-94381287;hs9:33808517-33808517,hs9:101171163-101171163;hs9:35191191-35191191,hs9:89719222-89719222;hs9:37579961-37579961,hs9:38356863-38356863;hs9:44091403-44091403,hs9:76284795-76284795;hs9:44109974-44109974,hs9:94341584-94341584;hs9:44115736-44115736,hs9:75845150-75845150;hs9:71415344-71415344,hs9:113721341-113721341;hs9:73090837-73090837,hs9:107510842-107510842;hs9:73118125-73118125,hs9:78797082-78797082;hs9:73140059-73140059,hs9:131043420-131043420;hs9:73140711-73140711,hs9:101147709-101147709;hs9:73211947-73211947,hs9:73212011-73212011;hs9:73212519-73212519,hs9:76645911-76645911;hs9:73733112-73733112,hs9:101153209-101153209;hs9:74342824-74342824,hs9:93972217-93972217;hs9:76617987-76617987,hs9:95143308-95143308;hs9:76866204-76866204,hs9:37506193-37506193;hs9:77264394-77264394,hs9:93417140-93417140;hs9:78237628-78237628,hs9:103832775-103832775;hs9:79781166-79781166,hs9:86618700-86618700;hs9:89180937-89180937,hs9:89720058-89720058;hs9:89188466-89188466,hs9:105605264-105605264;hs9:89710921-89710921,hs9:107510463-107510463;hs9:90767759-90767759,hs9:125993629-125993629;hs9:91436675-91436675,hs9:37863888-37863888;hs9:94641684-94641684,hs9:4481872-4481872;hs9:95419170-95419170,hs9:95419221-95419221;hs9:97649220-97649220,hs9:11953470-11953470;hs9:109054513-109054513,hs9:69951376-69951376;hs9:109054513-109054513,hs15:20040155-20040155;hs9:109330785-109330785,hs9:10012413-10012413;hs9:112051679-112051679,hs9:9748260-9748260;hs9:113720042-113720042,hs9:33512591-33512591;hs9:114921387-114921387,hs9:123226597-123226597;hs9:122290856-122290856,hs9:124634847-124634847;hs9:123341128-123341128,hs9:134248738-134248738;hs9:124690521-124690521,hs9:114076351-114076351;hs9:126725730-126725730,hs9:127008487-127008487;hs9:127014905-127014905,hs9:31506319-31506319;hs9:130783966-130783966,hs9:130784344-130784344;hs9:131059621-131059621,hs9:72870545-72870545;hs9:135232076-135232076,hs9:135257589-135257589;hs9:136365774-136365774,hs9:121369776-121369776;hs10:53964880-53964880,hs10:53966633-53966633;hs10:56675165-56675165,hs10:57343489-57343489;hs10:59667911-59667911,hs12:17091783-17091783;hs10:62196130-62196130,hs10:62232565-62232565;hs10:62729631-62729631,hs10:62734751-62734751;hs10:64187127-64187127,hs10:64187143-64187143;hs10:122701053-122701053,hs10:122937812-122937812;hs10:122763364-122763364,hs10:122979083-122979083;hs10:122785937-122785937,hs8:127868900-127868900;hs10:122962394-122962394,hs10:122969741-122969741;hs10:122968553-122968553,hs10:122590393-122590393;hs10:122976240-122976240,hs10:122983610-122983610;hs10:123221497-123221497,hs10:122874934-122874934;hs10:123443645-123443645,hs8:128554599-128554599;hs10:123571289-123571289,hs10:122492269-122492269;hs11:48354569-48354569,hs11:48354921-48354921;hs11:84479815-84479815,hs11:84501206-84501206;hs12:21477067-21477067,hs12:22077302-22077302;hs12:24787180-24787180,hs12:24788642-24788642;hs12:24933768-24933768,hs12:24935119-24935119;hs12:26194760-26194760,hs12:26195964-26195964;hs12:26371315-26371315,hs12:26373325-26373325;hs12:27285005-27285005,hs12:27799566-27799566;hs12:27321020-27321020,hs12:27327127-27327127;hs12:27357448-27357448,hs12:27358270-27358270;hs12:27797066-27797066,hs12:27799569-27799569;hs12:30785300-30785300,hs12:33614816-33614816;hs12:31156218-31156218,hs12:31161980-31161980;hs12:31167475-31167475,hs12:31358260-31358260;hs12:31440869-31440869,hs12:31817804-31817804;hs12:31471715-31471715,hs19:15337550-15337550;hs12:31472566-31472566,hs12:31722437-31722437;hs12:31491312-31491312,hs19:15467876-15467876;hs12:31577684-31577684,hs19:22821126-22821126;hs12:32175889-32175889,hs12:32275041-32275041;hs12:33324228-33324228,hs12:33326535-33326535;hs12:33615478-33615478,hs12:33622588-33622588;hs12:67817101-67817101,hs12:72701762-72701762;hs12:68027240-68027240,hs12:68083861-68083861;hs12:68258088-68258088,hs12:69689335-69689335;hs12:68258487-68258487,hs12:69957714-69957714;hs12:68281270-68281270,hs12:68555336-68555336;hs12:70100874-70100874,hs12:69750355-69750355;hs12:70208086-70208086,hs12:70212533-70212533;hs12:70892595-70892595,hs12:72800103-72800103;hs12:102591254-102591254,hs12:102591328-102591328;hs13:45457820-45457820,hs13:45460952-45460952;hs13:93916172-93916172,hs13:93916562-93916562;hs14:37327502-37327502,hs14:37286911-37286911;hs14:45321003-45321003,hs14:45431618-45431618;hs16:6890052-6890052,hs16:7200214-7200214;hs16:78824063-78824063,hs16:78792905-78792905;hs17:79116723-79116723,hs17:79091942-79091942;hs18:35437531-35437531,hs12:70285426-70285426;hs18:60152298-60152298,hs18:60153452-60153452;hs20:13996432-13996432,hs20:13999409-13999409;hs20:14150281-14150281,hs6:13191301-13191301;hs20:14831049-14831049,hs20:14926285-14926285;hs20:14962074-14962074,hs20:15818916-15818916;hs20:15060292-15060292,hs20:15098563-15098563;hsX:57767877-57767877,hsX:57770417-57770417;hsX:79449155-79449155,hsX:79365508-79365508;hsX:121727337-121727337,hsX:121727449-121727449 MACROD2;FHIT;ROR2;PTPRD;PHACTR1;NCKAP5;TRPM3;PPFIBP1;KDM4C;GABBR2;FAM60A;NIPSNAP3A;WWOX;PRKG1;RBFOX1;GPC6;DLG2;PCDH15;C12orf28;ZNF804A;SLC25A21;CPNE4;RAB3IP;SSPN;CDK5RAP2;LPPR1;TRHDE;AATK;RASSF8;RHOBTB1;LPAR1;ZNF365;DGKB;ANK3;DENND5B;PMCH;UBE2E3;REV3L;FBXL13;SH3GL2;SLC24A2;IPPK;PALM2-AKAP2;AKAP2;TTLL11;STRBP;PARK2;ITPR2;PIP5K1B;PACRG;CDKN2A;FRS2;LINGO2;DCAF10;IPO8;FAM154A;C2CD2;PRDM5;ADGB;TMEM108;CENPP;PCSK5;BICD1;KAZN;ABCA4;ATE1;SLCO1A2;ABCC9;METTL20;PARPBP;CENPJ;KLHL28;FAM179B;AKAP8;ZNF492;EXOC6B;KIF15;ZDHHC3;COA1;PDCD1LG2;TTC39B;CCDC171;UNC13B;PAX5;FBXO10;TMEM2;RORB;RMI1;FBP2;C9orf3;EPB41L4B;PALM2;SUSD1;RALGPS1;SWI5;TTF1;DDX31 Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes KDM4C,RALGPS1;KDM4C,STRBP;CCDC171,ROR2;EPB41L4B,PTPRD;SUSD1,CDK5RAP2 CTDB0191 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 7 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_1712 Illumina HiSeq 2000 hs1:12816831-12816831,hs1:12816902-12816902;hs1:31041604-31041604,hs16:71275724-71275724;hs1:59817320-59817320,hs1:59844697-59844697;hs1:71529231-71529231,hsX:31328661-31328661;hs1:106797137-106797137,hs8:141526846-141526846;hs1:107262017-107262017,hs22:29065465-29065465;hs1:151981298-151981298,hs18:47869228-47869228;hs1:159644820-159644820,hs2:213567335-213567335;hs1:174944448-174944448,hs1:174918820-174918820;hs1:177352586-177352586,hs1:182470371-182470371;hs1:179730323-179730323,hs7:105680981-105680981;hs1:185709201-185709201,hs1:216448097-216448097;hs1:185981239-185981239,hs1:216835281-216835281;hs1:217191564-217191564,hs5:124907266-124907266;hs1:219640045-219640045,hs1:219640183-219640183;hs1:245947948-245947948,hs1:245956002-245956002;hs1:246375399-246375399,hs1:246631795-246631795;hs2:61120457-61120457,hs2:61121114-61121114;hs2:138405097-138405097,hs2:138406320-138406320;hs2:138456532-138456532,hs3:40858075-40858075;hs2:141704155-141704155,hs2:142142851-142142851;hs2:182857564-182857564,hs4:166311017-166311017;hs2:182859200-182859200,hs8:107303845-107303845;hs2:183216609-183216609,hs8:107303722-107303722;hs2:213200448-213200448,hs15:60485418-60485418;hs2:227914316-227914316,hs13:92816952-92816952;hs3:40895919-40895919,hs3:40908081-40908081;hs3:60347184-60347184,hs3:60600529-60600529;hs3:60355603-60355603,hs3:60410921-60410921;hs3:60437886-60437886,hs3:60582078-60582078;hs3:60654722-60654722,hs3:60772062-60772062;hs3:60908135-60908135,hs3:60926290-60926290;hs3:60908135-60908135,hs3:60926290-60926290;hs3:61020615-61020615,hs3:60995050-60995050;hs3:61302385-61302385,hs3:61095057-61095057;hs3:109105633-109105633,hs8:107303681-107303681;hs3:161802083-161802083,hs22:29065418-29065418;hs3:175583584-175583584,hs3:175524660-175524660;hs3:180589466-180589466,hs14:37229570-37229570;hs3:188654784-188654784,hs12:13199088-13199088;hs4:17798390-17798390,hs4:17798694-17798694;hs4:63865499-63865499,hs5:15058946-15058946;hs4:64543184-64543184,hs5:31763167-31763167;hs4:159005035-159005035,hs15:57490955-57490955;hs4:160052706-160052706,hs7:87684219-87684219;hs4:162674024-162674024,hs4:162674200-162674200;hs4:190915166-190915166,hsY:9960767-9960767;hs5:838828-838828,hs5:746726-746726;hs5:1427980-1427980,hs5:6035460-6035460;hs5:3808419-3808419,hs5:15417884-15417884;hs5:3827134-3827134,hs5:5678760-5678760;hs5:5663912-5663912,hs5:12809514-12809514;hs5:5953927-5953927,hs5:12251543-12251543;hs5:12262532-12262532,hs5:33455015-33455015;hs5:15427959-15427959,hs5:1374405-1374405;hs5:19419092-19419092,hs12:14335048-14335048;hs5:37718571-37718571,hs5:37749425-37749425;hs5:103090161-103090161,hs15:60576708-60576708;hs5:122737778-122737778,hs12:53298489-53298489;hs5:136639638-136639638,hs5:136644408-136644408;hs5:137013627-137013627,hs3:83336421-83336421;hs5:150783720-150783720,hs5:150783919-150783919;hs5:150977985-150977985,hs8:107303418-107303418;hs5:174218204-174218204,hs5:174098797-174098797;hs5:177208417-177208417,hs5:177208978-177208978;hs6:1717602-1717602,hs6:1776679-1776679;hs6:2092034-2092034,hs6:2124532-2124532;hs6:27818424-27818424,hs6:27873359-27873359;hs6:40297475-40297475,hs6:40298410-40298410;hs6:40417300-40417300,hs6:113484203-113484203;hs6:40594883-40594883,hs6:40595961-40595961;hs6:40595378-40595378,hs6:40597115-40597115;hs6:40653798-40653798,hs8:47816993-47816993;hs6:40741996-40741996,hs6:40744063-40744063;hs6:40984676-40984676,hs6:43568980-43568980;hs6:41400672-41400672,hs6:41400927-41400927;hs6:42176522-42176522,hs6:42480731-42480731;hs6:42897140-42897140,hs9:67827469-67827469;hs6:43003017-43003017,hs6:42060545-42060545;hs6:43214551-43214551,hs6:43682227-43682227;hs6:43296818-43296818,hs6:43298150-43298150;hs6:43405832-43405832,hs6:41597257-41597257;hs6:43445951-43445951,hs7:108847802-108847802;hs6:43576209-43576209,hs6:47666433-47666433;hs6:43613979-43613979,hs6:43633906-43633906;hs6:43731110-43731110,hs6:43731289-43731289;hs6:43959002-43959002,hs6:43960648-43960648;hs6:44378943-44378943,hs6:149367977-149367977;hs6:44654070-44654070,hs6:50373254-50373254;hs6:45016550-45016550,hs6:141314896-141314896;hs6:45026134-45026134,hs6:48254082-48254082;hs6:47026776-47026776,hs6:76749327-76749327;hs6:47676722-47676722,hs6:113732776-113732776;hs6:47884066-47884066,hs6:52871284-52871284;hs6:47994063-47994063,hs6:141319767-141319767;hs6:48245761-48245761,hs6:116333808-116333808;hs6:48253886-48253886,hs6:47912968-47912968;hs6:48255194-48255194,hs6:114762952-114762952;hs6:48541540-48541540,hs6:139212269-139212269;hs6:48690816-48690816,hs6:114646951-114646951;hs6:50415992-50415992,hs6:44378174-44378174;hs6:50587881-50587881,hs6:114666278-114666278;hs6:50868645-50868645,hs6:44463470-44463470;hs6:52046455-52046455,hs6:76642581-76642581;hs6:52054548-52054548,hs6:43572450-43572450;hs6:55349027-55349027,hs6:113107998-113107998;hs6:57250580-57250580,hs6:139271856-139271856;hs6:58443143-58443143,hs6:58445022-58445022;hs6:73405066-73405066,hs12:71021907-71021907;hs6:88051759-88051759,hs6:88053814-88053814;hs6:113732797-113732797,hs6:141319765-141319765;hs6:115437956-115437956,hs6:118711213-118711213;hs6:116344138-116344138,hs6:113730344-113730344;hs6:120956856-120956856,hs6:56814774-56814774;hs6:122043651-122043651,hs12:98672891-98672891;hs6:131629497-131629497,hs6:131627547-131627547;hs6:139196925-139196925,hs10:19377576-19377576;hs6:155533097-155533097,hs6:159984325-159984325;hs6:155887996-155887996,hs6:159970992-159970992;hs6:159970981-159970981,hs7:159124496-159124496;hs6:159986963-159986963,hs6:162818898-162818898;hs6:163533350-163533350,hs6:154844643-154844643;hs7:169464-169464,hs7:22615139-22615139;hs7:991221-991221,hs7:991449-991449;hs7:991240-991240,hs7:139436199-139436199;hs7:2451194-2451194,hs7:2451496-2451496;hs7:2677469-2677469,hs14:65235219-65235219;hs7:22633594-22633594,hs7:22863373-22863373;hs7:22881337-22881337,hs10:15170733-15170733;hs7:24384705-24384705,hs8:107303583-107303583;hs7:24745029-24745029,hs7:37983085-37983085;hs7:34782741-34782741,hs7:40727684-40727684;hs7:40290702-40290702,hs7:45239362-45239362;hs7:40725547-40725547,hs7:42510261-42510261;hs7:40726430-40726430,hs7:45415035-45415035;hs7:41479387-41479387,hs7:41477471-41477471;hs7:45410800-45410800,hs7:46661738-46661738;hs7:46081461-46081461,hs7:48162112-48162112;hs7:47750430-47750430,hs7:34510647-34510647;hs7:48589396-48589396,hs7:45354779-45354779;hs7:48857472-48857472,hs7:140369865-140369865;hs7:51791450-51791450,hs7:51791647-51791647;hs7:103814602-103814602,hs12:40832796-40832796;hs7:105501010-105501010,hs7:123725904-123725904;hs7:108349872-108349872,hs9:116512521-116512521;hs7:119807066-119807066,hs7:124050407-124050407;hs7:123728844-123728844,hs7:124032788-124032788;hs7:139122351-139122351,hs14:65235083-65235083;hs7:146782298-146782298,hs7:146782218-146782218;hs7:158960306-158960306,hs7:104353342-104353342;hs8:6140424-6140424,hs8:6142053-6142053;hs8:8391675-8391675,hs8:9490908-9490908;hs8:9479717-9479717,hs8:9492161-9492161;hs8:9480098-9480098,hs8:9480402-9480402;hs8:13448380-13448380,hs8:13451985-13451985;hs8:24883166-24883166,hs8:30550253-30550253;hs8:26875506-26875506,hs3:132591922-132591922;hs8:40161589-40161589,hs8:40162166-40162166;hs8:47817159-47817159,hs6:40654902-40654902;hs8:107303641-107303641,hs16:59452513-59452513;hs8:141527249-141527249,hs1:106797148-106797148;hs9:4277875-4277875,hs9:28996052-28996052;hs9:5156215-5156215,hs9:134686620-134686620;hs9:5347532-5347532,hs9:37844008-37844008;hs9:10411052-10411052,hs9:10464672-10464672;hs9:32437701-32437701,hs9:33755221-33755221;hs9:68292966-68292966,hs6:43628644-43628644;hs9:72925583-72925583,hs9:72926108-72926108;hs9:78997027-78997027,hs12:53290974-53290974;hs9:78997038-78997038,hs12:53298844-53298844;hs9:79483887-79483887,hs9:79484590-79484590;hs9:116473744-116473744,hs9:116481161-116481161;hs9:134686767-134686767,hs9:29059065-29059065;hs10:18805801-18805801,hs6:112223804-112223804;hs10:38968739-38968739,hs10:38969292-38969292;hs10:39097513-39097513,hs15:47175301-47175301;hs10:45506974-45506974,hs10:45583686-45583686;hs10:49870431-49870431,hs2:113778149-113778149;hs11:30248513-30248513,hs11:30248612-30248612;hs11:35413489-35413489,hs15:85974311-85974311;hs11:50729947-50729947,hs11:50730005-50730005;hs11:83817149-83817149,hs15:60485420-60485420;hs11:90203335-90203335,hs11:90206602-90206602;hs11:132995521-132995521,hs11:132995671-132995671;hs12:3607591-3607591,hs6:65631001-65631001;hs12:9081855-9081855,hs12:9095837-9095837;hs12:9088429-9088429,hs12:9109837-9109837;hs12:25542238-25542238,hs12:25706545-25706545;hs12:25707482-25707482,hs12:25708018-25708018;hs12:25708724-25708724,hs12:41044819-41044819;hs12:29456699-29456699,hs12:42228577-42228577;hs12:37890266-37890266,hs12:37890328-37890328;hs12:40985675-40985675,hs12:26058854-26058854;hs12:41046628-41046628,hs12:25546938-25546938;hs12:42344363-42344363,hs12:20085011-20085011;hs12:45583508-45583508,hs12:42002880-42002880;hs12:47206251-47206251,hs12:47207822-47207822;hs12:53291406-53291406,hs12:53292466-53292466;hs12:53292682-53292682,hs12:53293563-53293563;hs12:53295858-53295858,hs12:53298440-53298440;hs12:53298841-53298841,hs1:192775466-192775466;hs12:71020045-71020045,hs6:156355267-156355267;hs12:127407679-127407679,hs12:127403442-127403442;hs13:47558462-47558462,hs13:47559964-47559964;hs13:113831882-113831882,hs13:113832015-113832015;hs14:37229044-37229044,hs14:37229571-37229571;hs14:78820285-78820285,hs14:78820553-78820553;hs15:28392591-28392591,hs15:31123915-31123915;hs15:81498584-81498584,hs15:81500251-81500251;hs16:23201766-23201766,hs16:23202291-23202291;hs16:26438659-26438659,hs16:26439527-26439527;hs16:31337667-31337667,hs6:159984711-159984711;hs16:32364918-32364918,hs6:161605354-161605354;hs16:64608434-64608434,hs8:107303675-107303675;hs16:72565541-72565541,hs16:72658874-72658874;hs16:78219813-78219813,hs16:78296245-78296245;hs16:78416682-78416682,hs16:78386125-78386125;hs16:78489133-78489133,hs16:78750211-78750211;hs16:88226611-88226611,hs16:29238671-29238671;hs17:5163775-5163775,hs17:5165528-5165528;hs17:10183478-10183478,hs17:17343607-17343607;hs17:17355457-17355457,hs17:25404201-25404201;hs18:47869668-47869668,hs1:151981286-151981286;hs19:1039663-1039663,hs19:6201412-6201412;hs19:7934235-7934235,hs19:7935176-7935176;hs19:10544434-10544434,hs19:10544509-10544509;hs19:11093440-11093440,hs19:10478824-10478824;hs19:32051896-32051896,hs19:32057163-32057163;hs19:39076205-39076205,hs19:39077640-39077640;hs19:39821110-39821110,hs19:39822285-39822285;hs19:39821110-39821110,hs19:39822285-39822285;hs19:39826652-39826652,hs6:115636102-115636102;hs19:41103727-41103727,hs19:57708314-57708314;hs19:47621603-47621603,hs19:47624066-47624066;hs19:49240774-49240774,hs19:49109177-49109177;hs19:49482490-49482490,hs19:49485891-49485891;hs19:56750004-56750004,hs19:56751681-56751681;hs20:14689997-14689997,hs20:15125858-15125858;hs20:14919637-14919637,hs20:14921988-14921988;hs20:15084652-15084652,hs20:15373150-15373150;hs20:23413088-23413088,hs20:23413279-23413279;hs20:23413277-23413277,hs4:5227198-5227198;hs20:29458940-29458940,hs20:29459033-29459033;hs20:58791770-58791770,hs20:59219264-59219264;hs21:24585634-24585634,hs21:32752859-32752859;hs21:24992061-24992061,hs21:24993122-24993122;hs21:25177184-25177184,hs21:26210651-26210651;hs21:38808019-38808019,hs21:38850944-38850944;hs22:29065409-29065409,hs22:29065465-29065465;hs22:47069898-47069898,hs22:46917025-46917025;hsX:26003128-26003128,hsX:26018312-26018312;hsX:121074666-121074666,hsX:121246206-121246206;hsX:145977030-145977030,hsX:145976974-145976974;hsX:150511397-150511397,hsX:150516590-150516590;hsX:154387770-154387770,hs20:54384091-54384091 FHIT;KRT8;OXR1;WWOX;MACROD2;TNKS;GMFG;TTC28;SMYD3;GMDS;IFLTD1;C7orf10;SLC25A21;POLH;RSPH9;PTCHD4;ADAP1;PTPRD;RABGAP1L;CNTNAP2;LRP1B;RYR1;STEAP1B;ZDHHC11;WDR70;FGGY;OPCML;CHST12;FAM153A;PTPRB;SAE1;DYRK1A;PRUNE2;FSTL5;THSD7B;SUPT3H;NRXN3;C1orf158;HMCN1;ESRRG;PHC1;SLC38A4;SPTB;IL16;SCNN1G;FLJ22184;PDE4A;GYS1;ZSCAN5A;REL;PPP1R1C;SPOCK1;CDC5L;GPR115;IMPG1;FRK;ECT2L;SMC5;DMD;PARK2;GPC5;DLG2;PACRG;EYS;LHFPL3;TIAM2;DST;TCF12;ERBB4;CHRAC1;ABCC10;ICK;DCAF10;GSR;FAM163A;SMARCA4;FXR1;HERC2;PRMT8;TIAM1;NPSR1;USH2A;CACNB2;KCNQ5;ABCA13;GLIS3;ZRANB2;RGSL1;NMT2;SLC1A2;M6PR;KLRG1;KIAA1467;FAR2;MUC19;PCID2;AKAP13;ITGAM;TYK2;LTBP4;FAM83E;RASIP1;ZNF264;PDE1A;COL4A4;CELSR1;GRAMD4;STK32B;RAPGEF2;CPE;ZDHHC11B;SLC6A3;PDZD2;TARS;CEP120;KLHL3;HIST1H2BN;LRFN2;MRPS10;CNPY3;TTBK1;TJAP1;IL17A;HMGCLL1;C6orf162;HS3ST5;REPS1;UST;AGPAT4;TTYH3;DFNA5;EPDR1;SFRP4;ADAM22;ORC5;ATXN7L1;HIPK2;DENND2A;ACO1;PRSS3 Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes TTYH3,SPTB;DFNA5,EPDR1;ORC5,MUC19 CTDB0192 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 8 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_3213 Illumina HiSeq 2000 hs1:46711933-46711933,hs10:120769130-120769130;hs1:72582491-72582491,hs11:93161840-93161840;hs1:80873015-80873015,hs8:129722303-129722303;hs1:101765018-101765018,hs13:41534121-41534121;hs1:120627397-120627397,hs1:145192062-145192062;hs1:120692163-120692163,hs1:145123375-145123375;hs1:144702126-144702126,hs1:144977345-144977345;hs1:148905300-148905300,hs2:91870460-91870460;hs1:149698390-149698390,hs1:149312320-149312320;hs1:155334771-155334771,hs1:154172782-154172782;hs1:160927231-160927231,hs1:162375797-162375797;hs1:173329823-173329823,hs20:462114-462114;hs1:174227555-174227555,hs1:174230251-174230251;hs1:245899383-245899383,hs1:248192421-248192421;hs2:91766771-91766771,hs4:4239554-4239554;hs2:91794476-91794476,hs4:4211063-4211063;hs2:122445668-122445668,hs2:122451702-122451702;hs2:205714975-205714975,hs2:205751233-205751233;hs3:5252525-5252525,hs3:5148269-5148269;hs3:7284521-7284521,hs3:7285405-7285405;hs3:59796220-59796220,hs3:59836620-59836620;hs3:59806996-59806996,hs3:59853062-59853062;hs3:60459555-60459555,hs3:60559733-60559733;hs3:75597092-75597092,hs8:6975483-6975483;hs3:75989533-75989533,hs20:26209237-26209237;hs3:79212330-79212330,hs3:79211577-79211577;hs3:85131715-85131715,hs3:85131657-85131657;hs3:105939461-105939461,hs22:29058973-29058973;hs3:141217420-141217420,hs3:89177273-89177273;hs4:119308257-119308257,hs8:128330605-128330605;hs4:183531845-183531845,hs12:25134981-25134981;hs4:190878715-190878715,hs9:68433480-68433480;hs5:1571536-1571536,hs5:23955190-23955190;hs5:5931196-5931196,hs5:5931074-5931074;hs5:8132880-8132880,hs5:21477317-21477317;hs5:9551007-9551007,hs5:38534100-38534100;hs5:9555327-9555327,hs5:37766871-37766871;hs5:9819127-9819127,hs5:11654210-11654210;hs5:11136242-11136242,hs19:27861601-27861601;hs5:11138002-11138002,hs5:42855354-42855354;hs5:11955478-11955478,hs5:11955714-11955714;hs5:12939554-12939554,hs6:109458429-109458429;hs5:15603965-15603965,hs5:42879398-42879398;hs5:17474504-17474504,hs5:21733260-21733260;hs5:18890491-18890491,hs5:18897263-18897263;hs5:19526432-19526432,hs5:18887557-18887557;hs5:19830290-19830290,hs6:119100825-119100825;hs5:19954549-19954549,hs5:19993465-19993465;hs5:20544561-20544561,hs6:107044917-107044917;hs5:20834825-20834825,hs5:34371606-34371606;hs5:21476552-21476552,hs5:43700211-43700211;hs5:23720361-23720361,hs6:106159507-106159507;hs5:23766624-23766624,hs5:16706761-16706761;hs5:23953529-23953529,hs5:43419821-43419821;hs5:24376405-24376405,hs5:24501760-24501760;hs5:24533228-24533228,hs5:24535954-24535954;hs5:33055160-33055160,hs6:111419835-111419835;hs5:33081192-33081192,hs6:115581082-115581082;hs5:33302300-33302300,hs5:34242360-34242360;hs5:33586106-33586106,hs5:33306984-33306984;hs5:34649924-34649924,hs5:44459522-44459522;hs5:34952356-34952356,hs5:34644217-34644217;hs5:37794607-37794607,hs5:40702223-40702223;hs5:38208294-38208294,hs5:38208076-38208076;hs5:40294605-40294605,hs6:108724875-108724875;hs5:40301381-40301381,hs5:40304982-40304982;hs5:40788424-40788424,hs5:41871132-41871132;hs5:42855354-42855354,hs5:11137878-11137878;hs5:43892322-43892322,hs6:106871281-106871281;hs5:44221728-44221728,hs5:43710859-43710859;hs5:50475816-50475816,hs5:29830800-29830800;hs5:67863731-67863731,hs12:25458653-25458653;hs5:77393076-77393076,hs20:44274315-44274315;hs6:12700130-12700130,hs6:12565631-12565631;hs6:29814678-29814678,hs12:133066751-133066751;hs6:39065440-39065440,hs3:63433011-63433011;hs6:65223953-65223953,hs9:11691181-11691181;hs6:68731346-68731346,hs6:68733783-68733783;hs6:106871183-106871183,hs6:106904801-106904801;hs6:106904824-106904824,hs6:106905158-106905158;hs6:107168622-107168622,hs6:107171535-107171535;hs6:108551650-108551650,hs6:115808146-115808146;hs6:108724619-108724619,hs6:108724864-108724864;hs6:109680039-109680039,hs6:108716011-108716011;hs6:112567968-112567968,hs6:112568344-112568344;hs6:112745653-112745653,hs6:108724625-108724625;hs6:116756575-116756575,hs6:117286031-117286031;hs6:144238951-144238951,hs11:74629676-74629676;hs7:61816513-61816513,hs16:33044225-33044225;hs7:113974234-113974234,hs7:113974362-113974362;hs7:132997011-132997011,hs7:132977415-132977415;hs7:136319239-136319239,hs22:29065771-29065771;hs7:155848556-155848556,hs7:155848614-155848614;hs8:388681-388681,hs8:10016819-10016819;hs8:388786-388786,hs8:10023493-10023493;hs8:1732256-1732256,hs8:129824744-129824744;hs8:1938545-1938545,hs8:111021211-111021211;hs8:1938700-1938700,hs22:24583709-24583709;hs8:2096170-2096170,hs8:118214855-118214855;hs8:2298171-2298171,hs8:2264513-2264513;hs8:2540739-2540739,hs8:108491358-108491358;hs8:3942451-3942451,hs8:3943319-3943319;hs8:5280174-5280174,hs8:10193235-10193235;hs8:5607746-5607746,hs8:9335398-9335398;hs8:5818083-5818083,hs8:122921054-122921054;hs8:6322177-6322177,hs8:6322538-6322538;hs8:6511163-6511163,hs8:48258384-48258384;hs8:6798363-6798363,hs8:6791105-6791105;hs8:6948641-6948641,hs8:12517780-12517780;hs8:6953291-6953291,hs8:12512881-12512881;hs8:6953523-6953523,hs8:12513252-12513252;hs8:7016501-7016501,hs8:7010435-7010435;hs8:7036320-7036320,hs8:7966159-7966159;hs8:7078495-7078495,hs8:12515938-12515938;hs8:7255345-7255345,hs8:7770499-7770499;hs8:7333456-7333456,hs8:7693212-7693212;hs8:7364858-7364858,hs8:7670380-7670380;hs8:7463948-7463948,hs8:11877684-11877684;hs8:7936944-7936944,hs3:125499043-125499043;hs8:8065033-8065033,hs8:12315771-12315771;hs8:8181537-8181537,hs8:9015855-9015855;hs8:8189416-8189416,hs8:131514106-131514106;hs8:8664525-8664525,hs8:8822420-8822420;hs8:8664525-8664525,hs8:8822420-8822420;hs8:8777016-8777016,hs8:8779148-8779148;hs8:9279938-9279938,hs8:9280552-9280552;hs8:9333291-9333291,hs8:84819959-84819959;hs8:9562914-9562914,hs8:111355167-111355167;hs8:9665673-9665673,hs7:80801695-80801695;hs8:10000195-10000195,hs8:1584545-1584545;hs8:10014250-10014250,hs8:124480753-124480753;hs8:10016233-10016233,hs8:10327311-10327311;hs8:10017191-10017191,hs8:10333820-10333820;hs8:10018130-10018130,hs8:126785355-126785355;hs8:10220519-10220519,hs8:120630525-120630525;hs8:10461561-10461561,hs8:13422592-13422592;hs8:10677336-10677336,hs8:114348051-114348051;hs8:10680674-10680674,hs8:13292087-13292087;hs8:10966411-10966411,hs8:10949328-10949328;hs8:11592381-11592381,hs8:13294864-13294864;hs8:11594367-11594367,hs8:11436113-11436113;hs8:11688030-11688030,hs8:131526911-131526911;hs8:11789270-11789270,hs8:12544555-12544555;hs8:11875099-11875099,hs11:3604841-3604841;hs8:11922701-11922701,hs8:12169200-12169200;hs8:11995460-11995460,hs8:11985928-11985928;hs8:12280528-12280528,hs12:8382323-8382323;hs8:12296523-12296523,hs8:12054179-12054179;hs8:12615350-12615350,hs8:12613006-12613006;hs8:13304783-13304783,hs8:99060719-99060719;hs8:13417072-13417072,hs8:10461561-10461561;hs8:13624459-13624459,hs8:114365197-114365197;hs8:13688692-13688692,hs8:98951129-98951129;hs8:82262089-82262089,hs8:82264953-82264953;hs8:83232622-83232622,hs11:32546999-32546999;hs8:83232786-83232786,hs11:32544021-32544021;hs8:84503624-84503624,hs8:10469645-10469645;hs8:90431443-90431443,hs8:90431840-90431840;hs8:99017254-99017254,hs8:129823139-129823139;hs8:99419523-99419523,hs8:99420063-99420063;hs8:100780406-100780406,hs8:113865966-113865966;hs8:102663178-102663178,hs8:111778060-111778060;hs8:109142039-109142039,hs16:85905002-85905002;hs8:109641638-109641638,hs8:130382832-130382832;hs8:111803611-111803611,hs8:122244135-122244135;hs8:114344596-114344596,hs8:9960358-9960358;hs8:114353110-114353110,hs8:114317898-114317898;hs8:115034400-115034400,hs8:119576611-119576611;hs8:115045768-115045768,hs8:119584001-119584001;hs8:115398825-115398825,hs8:117214181-117214181;hs8:118226907-118226907,hs8:2126198-2126198;hs8:119271270-119271270,hs8:115033772-115033772;hs8:120645077-120645077,hs8:124139124-124139124;hs8:121265647-121265647,hs8:128061246-128061246;hs8:121284525-121284525,hs8:128054371-128054371;hs8:122610624-122610624,hs8:131135468-131135468;hs8:122921326-122921326,hs8:5964756-5964756;hs8:126940220-126940220,hs8:128244247-128244247;hs8:128789803-128789803,hs8:128785427-128785427;hs8:129122117-129122117,hs8:129380814-129380814;hs8:129848367-129848367,hs8:131554199-131554199;hs8:130695465-130695465,hs8:130696216-130696216;hs8:131514115-131514115,hs8:131514216-131514216;hs8:131551966-131551966,hs8:129870407-129870407;hs8:132413832-132413832,hs8:132416405-132416405;hs9:9314853-9314853,hs9:9338594-9338594;hs9:9446734-9446734,hs9:9558832-9558832;hs9:18962759-18962759,hs9:18962522-18962522;hs9:30813294-30813294,hs9:30813460-30813460;hs9:105723635-105723635,hs9:105723686-105723686;hs9:115530694-115530694,hs9:118315728-118315728;hs9:122044021-122044021,hs9:122055529-122055529;hs9:122054068-122054068,hs8:84461832-84461832;hs10:9072541-9072541,hs10:9075408-9075408;hs10:21185544-21185544,hs10:32114299-32114299;hs10:24420749-24420749,hs10:27510158-27510158;hs10:24454362-24454362,hs10:32164744-32164744;hs10:29028150-29028150,hs10:34617346-34617346;hs10:42632546-42632546,hs16:32847298-32847298;hs10:69462186-69462186,hs11:73194932-73194932;hs10:78781568-78781568,hs10:78890218-78890218;hs10:135094671-135094671,hs10:135094375-135094375;hs11:12136783-12136783,hs11:8751085-8751085;hs11:14759183-14759183,hs11:8688349-8688349;hs11:15891772-15891772,hs11:19446353-19446353;hs11:16107909-16107909,hs11:16108518-16108518;hs11:16108820-16108820,hs11:16227719-16227719;hs11:21347640-21347640,hs11:22011183-22011183;hs11:23056505-23056505,hs11:4685874-4685874;hs11:32678922-32678922,hs11:32682955-32682955;hs11:38930907-38930907,hs11:38938294-38938294;hs11:47481274-47481274,hs11:47490788-47490788;hs11:66132063-66132063,hs18:248509-248509;hs11:67920789-67920789,hs11:67964723-67964723;hs11:67921701-67921701,hs11:67969634-67969634;hs11:68321657-68321657,hs11:73502963-73502963;hs11:68852666-68852666,hs11:68856210-68856210;hs11:71854185-71854185,hs11:71892233-71892233;hs11:73183697-73183697,hs11:73187509-73187509;hs11:73196166-73196166,hs11:73196410-73196410;hs11:79517841-79517841,hs11:79519404-79519404;hs11:80154665-80154665,hs11:80161246-80161246;hs11:82089386-82089386,hs11:113670622-113670622;hs11:82107062-82107062,hs11:113678657-113678657;hs12:3608099-3608099,hsX:115603998-115603998;hs12:21112171-21112171,hs12:21112253-21112253;hs12:21112171-21112171,hs12:21112253-21112253;hs12:21146050-21146050,hs12:24668263-24668263;hs12:21163855-21163855,hs12:25912293-25912293;hs12:24153752-24153752,hs12:25454564-25454564;hs12:24232639-24232639,hs12:24820979-24820979;hs12:24239268-24239268,hs12:24378923-24378923;hs12:24286488-24286488,hs12:24799318-24799318;hs12:24392736-24392736,hs12:24098440-24098440;hs12:24467761-24467761,hs12:24567310-24567310;hs12:24577222-24577222,hs12:25087229-25087229;hs12:24593438-24593438,hs12:25002783-25002783;hs12:24618361-24618361,hs12:25933764-25933764;hs12:24825444-24825444,hs12:25468205-25468205;hs12:24914727-24914727,hs12:25868108-25868108;hs12:25816707-25816707,hs12:25866520-25866520;hs12:25845830-25845830,hs12:25850921-25850921;hs12:26470412-26470412,hs12:24375283-24375283;hs12:26498192-26498192,hs12:24587021-24587021;hs12:26505675-26505675,hs12:26507296-26507296;hs12:26982944-26982944,hs12:26985005-26985005;hs12:27363537-27363537,hs12:27366013-27366013;hs12:27560093-27560093,hsX:102539937-102539937;hs12:27689163-27689163,hs12:27692825-27692825;hs12:30210762-30210762,hs12:25317871-25317871;hs12:128685871-128685871,hs12:128688065-128688065;hs13:105420995-105420995,hs13:105420720-105420720;hs14:21672602-21672602,hs14:21673185-21673185;hs14:90854732-90854732,hs14:91106289-91106289;hs14:91858272-91858272,hs14:91858493-91858493;hs14:106111177-106111177,hs14:106209397-106209397;hs16:33941951-33941951,hsY:10011307-10011307;hs16:78624172-78624172,hs16:78721356-78721356;hs16:78646114-78646114,hs16:78676141-78676141;hs16:78729510-78729510,hs16:78727043-78727043;hs18:41786184-41786184,hs18:53272991-53272991;hs18:41786248-41786248,hs18:48624085-48624085;hs18:41786809-41786809,hs18:53270416-53270416;hs18:41859841-41859841,hs18:48980138-48980138;hs18:41861096-41861096,hs18:43371215-43371215;hs18:43349762-43349762,hs18:53270142-53270142;hs18:43397838-43397838,hs19:35135388-35135388;hs18:48526730-48526730,hs18:48526797-48526797;hs18:48826577-48826577,hs18:48653189-48653189;hs18:48884723-48884723,hs18:48885993-48885993;hs18:48980487-48980487,hs18:41785986-41785986;hs18:48980509-48980509,hs18:53273232-53273232;hs18:51691757-51691757,hs18:52513092-52513092;hs18:51692472-51692472,hs18:57030345-57030345;hs18:52423444-52423444,hs18:53051200-53051200;hs18:52512616-52512616,hs18:41859688-41859688;hs18:53270146-53270146,hs18:55935551-55935551;hs18:53273482-53273482,hs18:43349816-43349816;hs18:53273612-53273612,hs18:51691880-51691880;hs18:55900077-55900077,hs18:41785682-41785682;hs19:37654428-37654428,hs19:37654805-37654805;hs19:54723812-54723812,hs19:54743518-54743518;hs20:1815540-1815540,hs20:1817105-1817105;hs20:1885048-1885048,hs20:31880828-31880828;hs20:14999831-14999831,hs20:15292946-15292946;hs20:15038841-15038841,hs20:15078185-15078185;hs20:30520969-30520969,hs20:30526707-30526707;hs21:33135507-33135507,hs21:33172991-33172991;hs22:28962413-28962413,hs22:31608716-31608716;hsX:6627807-6627807,hsX:6293395-6293395;hsX:31786717-31786717,hsX:31942743-31942743;hsX:49014302-49014302,hsX:49016211-49016211 MSRA;TCF4;FHIT;WWOX;SLCO1B3;SLCO1B7;SLCO1B3;CSMD3;ITPR2;CDH18;FAM168A;LACE1;MACROD2;PTPRD;SOX6;CTNND2;TTC28;DLC1;DBC1;MBD2;RAB27B;CDH10;SEPP1;SAMD12;DMD;PARD3B;RABGAP1L;CADM2;SMAD4;KCNMA1;GATA4;PPFIBP1;XKR6;EXOC4;GRM7;CSMD1;USP28;ARHGAP12;FAM154A;SOX7;SOX7;ENPP2;BCAT1;MFHAS1;MCPH1;ROBO1;FOXP2;KIAA1217;TUBGCP2;CCDC73;SUV420H1;CCDC88C;NEDD4L;ZNF585A;LILRB3;LILRA6;TTLL9;C5orf17;LAMA4;FBXO25;KBTBD11;SGK223;PINX1;AC130352.1;MATN2;COL14A1;ROBO2;PARD3;CASC1;SNX30;PDE4DIP;VPS13B;NELL1;EYS;CCDC67;PPP6R3;RTN4IP1;SOX5;XRRA1;SYNPR;FDFT1;CEP57L1;THOC1;TNKS;ANGPT1;CSNK2A1;PRMT8;MICAL2;ST5;PDE3B;MYO10;ASH1L;NEBL;ASAP1;EPHA3;KIAA0146;NEGR1;C1orf189;SH2D1B;OR2L13;ACBD5;TRIM66;NAV2;CELF1;SLC29A2;TPCN2;MRPL48;ARNTL2;FBRSL1;ELF1;TTC7B;SCGB2B2;SIRPA;BPIFB1;SUSD2;LIMK2;EDEM1;RASA2;OTOP1;TMEM128;TENM3;FRG1;FBXL7;ADAMTS12;DNAJC21;LIFR;PRKAA1;NNT;AP3B1;SNX3;SLC16A10;DSE;ZC2HC1B;DLGAP2;CLN8;DEFB107B;DEFB107A;RP1L1;DEFB130;USP17L2;DEFB130;GRHL2;WDR67 Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes KBTBD11,SUSD2;MSRA,DLGAP2;MSRA,ENPP2;GATA4,DLC1;ENPP2,WDR67 CTDB0193 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 18 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_3845 Illumina HiSeq 2000 hs1:69113072-69113072,hs1:69115367-69115367;hs1:73878392-73878392,hs22:29065566-29065566;hs1:75772648-75772648,hs12:41847723-41847723;hs1:79201648-79201648,hs1:79577132-79577132;hs1:184124974-184124974,hs1:184124797-184124797;hs1:216516019-216516019,hs1:216507900-216507900;hs1:235864000-235864000,hs1:235867946-235867946;hs1:246528229-246528229,hs1:246494790-246494790;hs2:43453622-43453622,hs2:43686088-43686088;hs2:91765062-91765062,hs2:91764992-91764992;hs2:139624940-139624940,hs6:157962378-157962378;hs2:145871813-145871813,hs2:146066383-146066383;hs2:171881079-171881079,hs12:14939656-14939656;hs2:209027352-209027352,hs6:108332298-108332298;hs3:60387844-60387844,hs3:60553593-60553593;hs3:60460501-60460501,hs3:60504662-60504662;hs3:60460501-60460501,hs3:60504662-60504662;hs3:71446126-71446126,hs8:22717711-22717711;hs3:167454947-167454947,hs3:167652922-167652922;hs3:175291231-175291231,hs3:175291356-175291356;hs4:95648337-95648337,hs4:95649750-95649750;hs5:30025549-30025549,hs5:30049532-30049532;hs5:59116252-59116252,hs5:59142420-59142420;hs5:102455060-102455060,hs5:102454816-102454816;hs5:163186102-163186102,hs11:46316545-46316545;hs6:23049976-23049976,hs22:29065880-29065880;hs6:42443406-42443406,hs7:91739514-91739514;hs6:71278966-71278966,hs6:155438242-155438242;hs6:113920867-113920867,hs6:121385577-121385577;hs6:120155454-120155454,hs6:122135650-122135650;hs6:120155624-120155624,hs6:133850889-133850889;hs6:120255362-120255362,hs6:113921033-113921033;hs6:133850604-133850604,hs6:165277581-165277581;hs6:147898453-147898453,hs6:147838086-147838086;hs6:157967739-157967739,hs6:157968471-157968471;hs6:157967739-157967739,hs6:157968471-157968471;hs6:157967914-157967914,hsX:33491045-33491045;hs6:165277482-165277482,hs6:122135732-122135732;hs7:30139059-30139059,hs7:30155476-30155476;hs7:44962408-44962408,hs7:44962719-44962719;hs7:52656804-52656804,hsY:9429664-9429664;hs7:77888211-77888211,hs14:71210733-71210733;hs7:110296970-110296970,hs7:110624926-110624926;hs7:110505190-110505190,hs7:110565576-110565576;hs7:110667526-110667526,hs7:110665784-110665784;hs7:117668504-117668504,hs7:117679569-117679569;hs7:117668868-117668868,hs9:119588371-119588371;hs7:128129991-128129991,hs11:32388070-32388070;hs8:57496946-57496946,hs4:56491227-56491227;hs8:87104824-87104824,hs14:31147626-31147626;hs8:124476615-124476615,hs8:124503115-124503115;hs8:141167084-141167084,hs8:141167425-141167425;hs10:54478955-54478955,hs14:31146030-31146030;hs10:59467201-59467201,hs10:59467326-59467326;hs10:62762266-62762266,hs13:103179993-103179993;hs10:68755092-68755092,hs10:68866332-68866332;hs10:113223222-113223222,hs14:59220674-59220674;hs10:118031089-118031089,hs10:118033744-118033744;hs11:66305148-66305148,hs11:66305467-66305467;hs11:74100610-74100610,hs11:74102831-74102831;hs11:88446035-88446035,hs11:88450626-88450626;hs12:17585082-17585082,hs12:17587927-17587927;hs12:24387412-24387412,hs12:26493371-26493371;hs12:24387737-24387737,hs12:25457096-25457096;hs12:24429229-24429229,hs12:24470525-24470525;hs12:24470049-24470049,hs12:28179225-28179225;hs12:24767220-24767220,hs12:24769270-24769270;hs12:24773553-24773553,hs12:26373765-26373765;hs12:25313198-25313198,hs12:26294294-26294294;hs12:25338655-25338655,hs12:25996541-25996541;hs12:25441706-25441706,hs12:25443502-25443502;hs12:25456694-25456694,hs12:25548073-25548073;hs12:25457258-25457258,hs12:25339221-25339221;hs12:25478701-25478701,hs12:26381999-26381999;hs12:25498649-25498649,hs12:28154287-28154287;hs12:25534701-25534701,hs12:25536326-25536326;hs12:25534881-25534881,hs12:26929291-26929291;hs12:25535897-25535897,hs12:25534721-25534721;hs12:25547201-25547201,hs12:26356494-26356494;hs12:25547686-25547686,hs12:25548196-25548196;hs12:25911509-25911509,hs12:28333090-28333090;hs12:25937804-25937804,hs12:25945118-25945118;hs12:25945660-25945660,hs12:28333288-28333288;hs12:26356649-26356649,hs12:26524788-26524788;hs12:26357435-26357435,hs12:24387409-24387409;hs12:26929480-26929480,hs12:25535892-25535892;hs12:28330336-28330336,hs12:25945117-25945117;hs12:28332768-28332768,hs12:28333081-28333081;hs12:29079890-29079890,hs12:29048414-29048414;hs12:29107111-29107111,hs12:29107265-29107265;hs12:29107119-29107119,hs12:29109488-29109488;hs12:83684206-83684206,hs12:83705809-83705809;hs12:99999903-99999903,hs12:100685315-100685315;hs13:89183158-89183158,hs14:31147883-31147883;hs13:89183164-89183164,hs14:31147565-31147565;hs14:31150728-31150728,hs14:86515632-86515632;hs14:71211086-71211086,hs7:77888197-77888197;hs15:100349144-100349144,hs15:100349234-100349234;hs16:10858717-10858717,hs16:10858555-10858555;hs16:73018393-73018393,hs16:73085774-73085774;hs16:78541610-78541610,hs16:78842929-78842929;hs16:78628492-78628492,hs16:78678496-78678496;hs16:78688258-78688258,hs16:78729961-78729961;hs16:78737379-78737379,hs16:78782211-78782211;hs18:626936-626936,hsX:150454645-150454645;hs18:1500899-1500899,hs18:10239106-10239106;hs18:8563290-8563290,hs18:42442098-42442098;hs18:9608759-9608759,hs18:9608843-9608843;hs18:10916543-10916543,hs18:42800744-42800744;hs18:13967775-13967775,hs18:44880221-44880221;hs18:14379781-14379781,hs18:28298422-28298422;hs18:18842407-18842407,hs18:53004169-53004169;hs18:22335340-22335340,hs18:43003627-43003627;hs18:22336064-22336064,hs18:42442244-42442244;hs18:24012368-24012368,hs18:53163074-53163074;hs18:34340072-34340072,hs18:18842123-18842123;hs18:44396866-44396866,hs18:18842194-18842194;hs18:53004345-53004345,hs18:53163072-53163072;hs18:53162699-53162699,hs18:53207622-53207622;hs18:53375819-53375819,hs18:43003626-43003626;hs18:53375821-53375821,hs18:22335232-22335232;hs20:52451641-52451641,hs20:52451124-52451124;hs21:22021973-22021973,hs14:59220583-59220583;hs21:36257690-36257690,hs21:36252702-36252702;hs21:36258998-36258998,hs21:36316326-36316326;hsX:79944913-79944913,hsX:79877371-79877371 WWOX;FHIT;SSPN;ZDHHC14;TCF4;IMMP2L;CCDC91;SCFD1;ITPR2;RUNX1;CASC1;GREB1L;SLC14A2;TTC28;SMYD3;NAALADL2;CTNNA3;PDE4D;THADA;MAP3K9;SAMD5;MAGI2;ZFHX3;TRAPPC9;PLEKHA8;LYST;USH2A;ZDHHC24;PGM2L1;GRM5;CTD-2054N24.2;NUBP1;PPP4R1;SETBP1;GIN1;EYA4;LRRTM3;ANKS1B;TIAM2;NMU;CREB3L1;PDZRN4;FHOD3;PIEZO2;ASTN2;FOXP1;SLC44A5;GFRA1;WBP11;SCYL2;CLUL1;PIAS2;ZFP36L2;TLK1;CRYGA;SERPINI1;C6orf57;AKAP9;METTL2B;PEBP4;ATP6V0D2;BRWD3 Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes FHOD3,GREB1L CTDB0194 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 10 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0023 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0195 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 8 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0031 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0196 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 10 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0052 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0197 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 11 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0053 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0198 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 1 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0008 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0199 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 9 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0010 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0200 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 8 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0015 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0201 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 5 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0021 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0202 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 6 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_40325 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0203 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 5 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_40328 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0204 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 8 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_40357 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0205 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 22 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_40336 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0206 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 16 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_6003 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0207 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 10 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_40364 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0208 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 7 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_40365 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0209 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 18 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0001 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0210 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 8 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0056 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0211 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 3 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0061 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0212 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 9 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0063 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0213 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 10 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_0572 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0214 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 6 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_1642 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0215 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 9 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_2442 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0216 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 8 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_3519 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0217 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 9 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_6005 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0218 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 14 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_6036 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0219 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 12 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_6039 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0220 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 18 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_6040 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0221 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 1 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_6052 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0222 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 5 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_6081 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0223 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 1 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_6082 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0224 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 2 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_6087 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0225 Research 25351503 Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderso Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun 2014 Oct 1 Esophageal adenocarcinoma Next Generation Sequencing Homo sapiens OESO_6091 Illumina BeadChip Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. GRCh37/hg19 EGAS00001000750 Yes NA CTDB0226 Research 23410887 Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA, Layer RM, Quinlan AR, Hall IM Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms Genome Research 2013 May 1 Glioblastoma Next Generation Sequencing Homo sapiens GBM_3_T Illumina paired-end sequencing chr1:1473900-1483900:-1;chr1:16337864-16347864:1;chr1:31188956-31198956:-1;chr1:31406425-31416425:1;chr1:43875362-43885362:-1;chr1:43910380-43920380:1;chr1:47724126-47734126:1;chr1:47833374-47843374:-1;chr1:68864547-68874547:-1;chr1:69203040-69213040:1;chr1:115424482-115434482:1;chr1:152583725-152593725:-1;chr1:202564758-202574758:1;chr1:209875072-209885072:1;chr1:222848998-222858998:-1;chr1:222869277-222879277:-1;chr2:124605911-124615911:1;chr2:239782842-239792842:-1;chr3:66288911-66298911:-1;chr4:49222803-49232803:1;chr4:59792957-59802957:-1;chr4:167586041-167596041:-1;chr5:469679-479679:1;chr5:143961445-143971445:1;chr6:17684703-17694703:1;chr6:63598668-63608668:-1;chr6:87836217-87846217:1;chr6:87903230-87913230:-1;chr6:119213764-119223764:-1;chr6:148704461-148714461:1;chr6:157709391-157719391:-1;chr7:20871764-20881764:-1;chr7:45342151-45352151:1;chr7:54442601-54452601:-1;chr7:55364942-55374942:1;chr7:64008939-64018939:1;chr7:74119690-74129690:-1;chr7:89691813-89701813:1;chr7:98889464-98899464:-1;chr7:99049088-99059088:1;chr7:155117625-155127625:-1;chr8:537803-547803:-1;chr8:124059516-124069516:-1;chr8:144031199-144041199:-1;chr9:33497840-33507840:1;chr9:33828151-33838151:-1;chr9:88059120-88069120:1;chr12:155502-165502:-1;chr12:58012428-58022428:1;chr12:58124857-58134857:-1;chr12:58165193-58175193:1;chr12:58293239-58303239:-1;chr12:59585626-59595626:1;chr12:60070221-60080221:-1;chr12:60240803-60250803:1;chr12:60312049-60322049:-1;chr12:60896441-60906441:1;chr12:61189444-61199444:-1;chr12:61528736-61538736:1;chr12:62372141-62382141:-1;chr12:62397311-62407311:1;chr12:62454499-62464499:-1;chr12:62540747-62550747:-1;chr12:62556039-62566039:1;chr12:62586105-62596105:1;chr12:62606297-62616297:1;chr12:63092161-63102161:-1;chr12:63193292-63203292:1;chr12:64501633-64511633:-1;chr12:64703554-64713554:1;chr12:65518347-65528347:-1;chr12:65548635-65558635:1;chr12:65593703-65603703:-1;chr12:65628803-65638803:1;chr12:66252334-66262334:-1;chr12:66282585-66292585:1;chr12:67222929-67232929:-1;chr12:67374611-67384611:1;chr12:68503822-68513822:-1;chr12:68538847-68548847:1;chr12:69109888-69119888:-1;chr12:69135193-69145193:-1;chr12:69262332-69272332:1;chr12:69629710-69639710:-1;chr12:69664804-69674804:1;chr12:69753079-69763079:-1;chr12:70038769-70048769:1;chr12:70571382-70581382:-1;chr12:70671527-70681527:1;chr12:71402327-71412327:-1;chr12:71608784-71618784:1;chr12:73090452-73100452:1;chr12:73591943-73601943:-1;chr12:74657443-74667443:1;chr12:74770975-74780975:-1;chr12:76372914-76382914:1;chr12:79055800-79065800:1;chr12:80167827-80177827:-1;chr12:80223100-80233100:1;chr12:80345783-80355783:-1;chr12:81462149-81472149:-1;chr12:82694720-82704720:1;chr12:83581735-83591735:1;chr12:83868047-83878047:-1;chr12:84779568-84789568:1;chr12:85123639-85133639:-1;chr12:122584226-122594226:-1;chr12:124445485-124455485:1;chr12:124536239-124546239:-1;chr13:58210070-58220070:-1;chr13:58422511-58432511:1;chr13:114448806-114458806:-1;chr14:19450369-19460369:-1;chr14:19479572-19489572:1;chr14:77379686-77389686:-1;chr14:77793984-77803984:1;chr14:87492583-87502583:1;chr14:106064937-106074937:1;chr16:628413-638413:-1;chr16:53450723-53460723:-1;chr17:20654872-20664872:-1;chr17:41101455-41111455:-1;chr17:41117231-41127231:-1;chr17:73137170-73147170:-1;chr17:73305559-73315559:1;chr17:73490192-73500192:1;chr19:15352967-15362967:-1;chr19:22633246-22643246:-1;chr19:22693818-22703818:1;chr19:39654171-39664171:1;chr19:42001729-42011729:1;chr19:44917853-44927853:-1;chr19:45563362-45573362:1;chr19:54090926-54100926:-1;chr20:29543855-29553855:-1;chr20:34954187-34964187:-1;chr20:60495841-60505841:1;chr21:10637520-10647520:-1;chr22:17229291-17239291:-1;chr22:20191610-20201610:-1;chr22:22729659-22739659:1;chr22:22761513-22771513:-1;chr22:23613231-23623231:1;chr22:24092290-24102290:1;chr22:24154290-24164290:-1;chr22:24522084-24532084:-1;chr22:26276205-26286205:1;chr22:50776853-50786853:-1;chrX:129043680-129053680:-1;chrX:129100675-129110675:1;chrY:9896479-9906479:-1 hs1:31195314-31195486,hs1:31409176-31409467;hs1:68848516-68848729,hs1:69012083-69012312;hs1:209878533-209878812,hs1:211252936-211253159;hs1:209879248-209879475,hs1:211279556-211279907;hs1:210967918-210968127,hs1:211278665-211278930;hs1:210968042-210968182,hs1:218774393-218774514;hs1:210968056-210968193,hs1:222857715-222857949;hs1:210968255-210968506,hs1:218778799-218779082;hs1:211253088-211253356,hs1:218778997-218779285;hs1:211253245-211253413,hs1:218779174-218779372;hs1:211277937-211278053,hs1:218774395-218774531;hs1:211279261-211279507,hs1:222862505-222862786;hs1:211279875-211279985,hs1:218779009-218779148;hs1:218774393-218774516,hs1:218779139-218779349;hs7:32396769-32397029,hs7:32406271-32406481;hs7:46160967-46161151,hs7:51162404-51162650;hs7:51080387-51080715,hs7:54949871-54950175;hs7:54510018-54510254,hs7:54524204-54524390;hs7:54671300-54671479,hs7:55352155-55352347;hs7:54896110-54896364,hs7:55775806-55776051;hs7:54910860-54911054,hs7:54919401-54919573;hs7:55110821-55110968,hs7:55111740-55111900;hs12:58138193-58138438,hs12:64521941-64522115;hs12:58599562-58599739,hs12:60903946-60904122;hs12:58600850-58601111,hs12:124420872-124421114;hs12:59311359-59311574,hs12:59313341-59313479;hs12:59592449-59592594,hs12:80171991-80172152;hs12:60073188-60073451,hs12:80228529-80228818;hs12:60317481-60317603,hs12:77202966-77203145;hs12:60655489-60655799,hs12:78409534-78409798;hs12:61531349-61531488,hs12:77501744-77502004;hs12:62456456-62456753,hs12:65892777-65893137;hs12:62550201-62550533,hs12:62560273-62560559;hs12:62552224-62552441,hs12:69831607-69831875;hs12:62587946-62588237,hs12:63200077-63200349;hs12:62612766-62612983,hs12:82153184-82153313;hs12:63099238-63099523,hs12:65596073-65596359;hs12:64521903-64522146,hs12:69939886-69940186;hs12:64575640-64575995,hs12:69136868-69137331;hs12:64615283-64615496,hs12:69767402-69767621;hs12:65524259-65524570,hs12:69581132-69581462;hs12:65554308-65554572,hs12:69669612-69669952;hs12:65566685-65566883,hs12:68988668-68988874;hs12:65578720-65579029,hs12:65892287-65892530;hs12:65579404-65579581,hs12:66294219-66294505;hs12:65579734-65580021,hs12:69891884-69892166;hs12:65601161-65601531,hs12:69267633-69267970;hs12:65633206-65633469,hs12:70044879-70045133;hs12:66257621-66257782,hs12:71080276-71080482;hs12:66286084-66286339,hs12:67227786-67227957;hs12:66296552-66296833,hs12:71081798-71082100;hs12:67379061-67379314,hs12:68988465-68988655;hs12:68510059-68510386,hs12:69632577-69633026;hs12:68546067-68546410,hs12:70673785-70674103;hs12:69184478-69184766,hs12:70002231-70002493;hs12:69226466-69226774,hs12:69228226-69228550;hs12:69272123-69272381,hs12:83587607-83587828;hs12:69755691-69756008,hs12:70578656-70578967;hs12:70057164-70057475,hs12:83517542-83517823;hs12:70065189-70065344,hs12:70248007-70248160;hs12:72041675-72041921,hs12:80836068-80836292;hs12:72186378-72186595,hs12:74670111-74670253;hs12:72885360-72885620,hs12:74773080-74773303;hs12:73112992-73113098,hs12:76939045-76939169;hs12:75922521-75922731,hs12:77201887-77202088;hs12:76032207-76032447,hs12:84788668-84788895;hs12:76916883-76917160,hs12:124450272-124450469;hs12:76917657-76917786,hs12:84692016-84692215;hs12:80975344-80975537,hs12:81866652-81866915;hs12:83875380-83875532,hs12:84693132-84693335;hs19:42612974-42613206,hs19:45450085-45450215;hsX:129051101-129051384,hsX:129105290-129105557 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22903, USA Tumor genomes are generally thought to evolve through a gradual accumulation of mutations, but the observation that extraordinarily complex rearrangements can arise through single mutational events suggests that evolution may be accelerated by punctuated changes in genome architecture. To assess the prevalence and origins of complex genomic rearrangements (CGRs), we mapped 6179 somatic structural variation breakpoints in 64 cancer genomes from seven tumor types and screened for clusters of three or more interconnected breakpoints. We find that complex breakpoint clusters are extremely common: 154 clusters comprise 25% of all somatic breakpoints, and 75% of tumors exhibit at least one complex cluster. Based on copy number state profiling, 63% of breakpoint clusters are consistent with being CGRs that arose through a single mutational event. CGRs have diverse architectures including focal breakpoint clusters, large-scale rearrangements joining clusters from one or more chromosomes, and staggeringly complex chromothripsis events. Notably, chromothripsis has a significantly higher incidence in glioblastoma samples (39%) relative to other tumor types (9%). Chromothripsis breakpoints also show significantly elevated intra-tumor allele frequencies relative to simple SVs, which indicates that they arise early during tumorigenesis or confer selective advantage. Finally, assembly and analysis of 4002 somatic and 6982 germline breakpoint sequences reveal that somatic breakpoints show significantly less microhomology and fewer templated insertions than germline breakpoints, and this effect is stronger at CGRs than at simple variants. These results are inconsistent with replication-based models of CGR genesis and strongly argue that nonhomologous repair of concurrently arising DNA double-strand breaks is the predominant mechanism underlying complex cancer genome rearrangements. GRCh37/hg19 Yes NA CTDB0227 Research 23410887 Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA, Layer RM, Quinlan AR, Hall IM Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms Genome Research 2013 May 1,6 Glioblastoma Next Generation Sequencing Homo sapiens GBM_6_T Illumina paired-end sequencing chr1:1473900-1483900:-1;chr1:2521600-2531600:-1;chr1:3525417-3535417:-1;chr1:3647544-3657544:-1;chr1:6566092-6576092:-1;chr1:10690627-10700627:1;chr1:10750727-10760727:-1;chr1:16337864-16347864:1;chr1:19640396-19650396:1;chr1:19685816-19695816:-1;chr1:19986058-19996058:-1;chr1:20006119-20016119:1;chr1:20056956-20066956:-1;chr1:20087301-20097301:1;chr1:20254351-20264351:-1;chr1:20409487-20419487:-1;chr1:20470024-20480024:1;chr1:20566051-20576051:-1;chr1:20601455-20611455:1;chr1:20696778-20706778:-1;chr1:20772022-20782022:1;chr1:20883534-20893534:-1;chr1:20950416-20960416:-1;chr1:21027094-21037094:1;chr1:21092856-21102856:-1;chr1:21113032-21123032:1;chr1:21259892-21269892:-1;chr1:21351936-21361936:1;chr1:21403767-21413767:-1;chr1:21431021-21441021:1;chr1:21461513-21471513:-1;chr1:21491828-21501828:1;chr1:21558977-21568977:-1;chr1:21649910-21659910:1;chr1:21695619-21705619:-1;chr1:22222941-22232941:1;chr1:22438882-22448882:-1;chr1:22615171-22625171:1;chr1:22705692-22715692:-1;chr1:22816690-22826690:1;chr1:22997192-23007192:-1;chr1:23083308-23093308:1;chr1:23193705-23203705:-1;chr1:23422971-23432971:1;chr1:23514145-23524145:-1;chr1:23596875-23606875:1;chr1:23704077-23714077:-1;chr1:23780199-23790199:1;chr1:23878040-23888040:-1;chr1:23980014-23990014:1;chr1:24501860-24511860:1;chr1:24801166-24811166:-1;chr1:24897468-24907468:1;chr1:24979137-24989137:-1;chr1:25288246-25298246:-1;chr1:25467300-25477300:1;chr1:26318928-26328928:-1;chr1:26501206-26511206:1;chr1:26597718-26607718:-1;chr1:26693804-26703804:1;chr1:26744918-26754918:-1;chr1:51123495-51133495:1;chr1:51174170-51184170:1;chr1:51238407-51248407:-1;chr1:51273496-51283496:1;chr1:51387913-51397913:-1;chr1:51408017-51418017:1;chr1:51449236-51459236:-1;chr1:51566894-51576894:-1;chr1:51673486-51683486:1;chr1:51750500-51760500:-1;chr1:51780885-51790885:1;chr1:51855772-51865772:-1;chr1:52076512-52086512:1;chr1:52146872-52156872:-1;chr1:52270909-52280909:1;chr1:52377102-52387102:-1;chr1:52417628-52427628:1;chr1:52448104-52458104:-1;chr1:52484622-52494622:1;chr1:52535507-52545507:-1;chr1:211617042-211627042:1;chr1:211631813-211641813:-1;chr1:214152730-214162730:1;chr1:214167730-214177730:-1;chr2:230960440-230970440:1;chr2:239782842-239792842:-1;chr2:240820510-240830510:-1;chr4:59792957-59802957:-1;chr4:167586041-167596041:-1;chr5:663946-673946:1;chr5:2760315-2770315:-1;chr5:138855975-138865975:1;chr6:119213764-119223764:-1;chr6:157709391-157719391:-1;chr6:168039630-168049630:-1;chr7:667269-677269:-1;chr7:1598617-1608617:-1;chr7:2506126-2516126:1;chr7:2596729-2606729:-1;chr7:5659032-5669032:-1;chr7:44279616-44289616:-1;chr7:149462471-149472471:1;chr7:149522848-149532848:-1;chr7:152432864-152442864:-1;chr7:155117625-155127625:-1;chr8:124059516-124069516:-1;chr8:144031199-144041199:-1;chr8:145528164-145538164:1;chr9:21907540-21917540:1;chr9:24150723-24160723:-1;chr9:26514723-26524723:-1;chr9:32060541-32070541:-1;chr9:126109648-126119648:1;chr9:126139667-126149667:-1;chr9:136213639-136223639:-1;chr9:136248838-136258838:1;chr9:138619282-138629282:1;chr9:138679370-138689370:-1;chr9:138862249-138872249:1;chr9:141006140-141016140:1;chr10:12001321-12011321:1;chr10:12012713-12022713:-1;chr10:81773746-81783746:1;chr10:121171302-121181302:-1;chr11:30249327-30259327:1;chr11:30328866-30338866:-1;chr11:40380151-40390151:1;chr11:48755267-48765267:-1;chr11:51568754-51578754:1;chr11:134778402-134788402:1;chr12:155502-165502:-1;chr12:17263319-17273319:1;chr12:17447189-17457189:-1;chr12:34740762-34750762:1;chr12:79841174-79851174:1;chr13:38358954-38368954:1;chr13:53193282-53203282:-1;chr13:114448806-114458806:-1;chr14:24875612-24885612:-1;chr14:25417064-25427064:1;chr14:25749566-25759566:1;chr14:25784804-25794804:-1;chr15:22756137-22766137:-1;chr16:1586111-1596111:-1;chr16:1806170-1816170:1;chr16:4742669-4752669:-1;chr16:5618596-5628596:1;chr16:5643705-5653705:-1;chr16:7325181-7335181:-1;chr16:29703944-29713944:1;chr16:86536282-86546282:1;chr16:86546282-86556282:-1;chr16:88470192-88480192:1;chr17:79048163-79058163:1;chr17:80178649-80188649:1;chr17:80193818-80203818:-1;chr18:44493642-44503642:1;chr18:44559606-44569606:-1;chr20:1191001-1201001:1;chr21:10637520-10647520:-1;chr21:37684565-37694565:-1;chr21:45690014-45700014:1;chr22:17229291-17239291:-1;chr22:25644294-25654294:1;chrX:48804133-48814133:-1;chrX:48824297-48834297:1;chrY:13854059-13864059:1;chrY:21039495-21049495:-1;chrY:22470477-22480477:-1;chrY:28457355-28467355:-1 hs1:16858031-16858170,hs1:26467148-26467359;hs1:16872902-16873149,hs1:23409085-23409958;hs1:16891620-16891712,hs1:27097263-27097391;hs1:16902182-16902273,hs1:19777334-19777499;hs1:16907147-16907385,hs1:19531822-19532121;hs1:16918973-16919354,hs1:20967413-20967782;hs1:16926484-16926575,hs1:51678307-51678456;hs1:16931086-16931440,hs1:52246624-52246980;hs1:16941934-16942230,hs1:26790271-26790587;hs1:16949971-16950160,hs1:51786242-51786440;hs1:16957630-16957863,hs1:22219054-22219282;hs1:16962997-16963222,hs1:23784323-23784516;hs1:17007788-17007994,hs1:19876655-19876985;hs1:17051396-17051603,hs1:20351341-20351546;hs1:17052226-17052537,hs1:51608058-51608383;hs1:17083460-17083617,hs1:21215470-21215618;hs1:17215609-17215912,hs1:19496737-19497075;hs1:17219862-17220176,hs1:19466861-19467239;hs1:19434616-19434972,hs6:123945393-123945757;hs1:19453820-19454218,hs1:27095450-27095845;hs1:19482733-19483100,hs1:90547252-90547618;hs1:19490684-19490955,hs1:27072104-27072383;hs1:19509419-19509764,hs1:52491010-52491352;hs1:19531799-19531883,hs1:24850909-24851046;hs1:19555514-19555729,hs1:52452035-52452246;hs1:19572222-19572553,hs1:26447563-26447894;hs1:19578292-19578609,hs1:19784998-19785314;hs1:19589165-19589484,hs1:234918419-234918751;hs1:19604056-19604272,hs1:19634487-19634800;hs1:19605281-19605591,hs1:24733905-24734256;hs1:19690436-19690785,hs1:20619961-20620320;hs1:19727477-19727856,hs1:26308973-26309355;hs1:19754540-19754761,hs1:26674692-26674959;hs1:19768737-19769010,hs1:21910901-21911193;hs1:19778834-19779180,hs1:21896177-21896548;hs1:19790551-19790673,hs1:21711805-21711988;hs1:19884786-19885109,hs1:19910455-19910738;hs1:19894552-19894874,hs1:19988797-19989144;hs1:19906367-19906477,hs1:26617309-26617423;hs1:19908656-19908759,hs1:23409301-23409600;hs1:19908663-19908768,hs1:23409322-23409552;hs1:20009609-20009766,hs1:22167468-22167642;hs1:20065009-20065346,hs1:23793219-23793569;hs1:20093444-20093793,hs1:27026765-27027108;hs1:20260642-20261014,hs1:26383539-26383916;hs1:20321690-20321785,hs1:26414019-26414229;hs1:20327404-20327763,hs1:26359407-26359779;hs1:20399022-20399105,hs1:21038950-21039077;hs1:20406184-20406496,hs1:22855369-22855646;hs1:20473097-20473314,hs1:26799617-26799792;hs1:20701274-20701462,hs1:20726937-20727314;hs1:20719749-20720117,hs1:26472249-26472593;hs1:20890468-20890823,hs1:21598283-21598625;hs1:20907693-20908016,hs1:23068659-23069027;hs1:20911514-20911877,hs1:26154793-26155138;hs1:20916714-20917077,hs1:20926398-20926783;hs1:20952064-20952420,hs1:22570408-22570794;hs1:20954924-20955122,hs1:51862189-51862488;hs1:21011772-21011884,hs1:51709615-51709716;hs1:21011963-21012118,hs1:24736718-24736843;hs1:21014966-21015291,hs1:22120227-22120542;hs1:21023269-21023369,hs1:26421480-26421616;hs1:21024976-21025262,hs1:21881458-21881773;hs1:21056474-21056729,hs1:24628350-24628697;hs1:21058826-21059104,hs1:26384470-26384826;hs1:21096263-21096400,hs1:26751948-26752167;hs1:21096521-21096625,hs1:22578487-22578589;hs1:21116861-21117082,hs1:23406562-23406874;hs1:21184774-21185109,hs1:23306694-23307068;hs1:21192682-21192952,hs1:25462013-25462373;hs1:21207962-21208132,hs1:24196033-24196247;hs1:21210918-21211275,hs1:25406592-25406983;hs1:21211792-21211878,hs1:25376578-25376783;hs1:21232568-21232810,hs1:21263808-21264174;hs1:21262680-21262985,hs1:25965554-25965827;hs1:21263163-21263459,hs1:24972934-24973094;hs1:21263413-21263533,hs1:21279448-21279576;hs1:21269977-21270327,hs1:25550561-25550931;hs1:21273146-21273511,hs1:26122360-26122754;hs1:21279297-21279461,hs1:24972939-24973093;hs1:21280552-21280857,hs1:26688637-26688973;hs1:21294446-21294792,hs1:26265898-26266263;hs1:21306834-21307131,hs1:23004554-23004887;hs1:21333029-21333295,hs1:22741836-22742136;hs1:21334719-21335093,hs1:22176305-22176650;hs1:21335972-21336121,hs1:24850836-24851221;hs1:21410955-21411326,hs1:26048471-26048852;hs1:21426399-21426697,hs1:23409561-23409890;hs1:21427851-21428052,hs1:23237042-23237284;hs1:21435053-21435276,hs1:22482377-22482647;hs1:21467888-21468196,hs1:22574656-22574955;hs1:21495501-21495743,hs1:21596691-21596915;hs1:21554725-21554984,hs1:23822063-23822358;hs1:21556141-21556498,hs1:22553631-22553989;hs1:21556732-21557087,hs1:26063337-26063713;hs1:21565908-21565990,hs1:26358585-26358696;hs1:21566019-21566257,hs1:22577192-22577442;hs1:21583073-21583418,hs1:26752023-26752396;hs1:21585658-21585752,hs1:23519314-23519422;hs1:21606820-21606945,hs1:51756765-51756877;hs1:21654353-21654602,hs1:26033184-26033443;hs1:21654630-21654719,hs1:22491153-22491256;hs1:21699639-21699973,hs1:21827150-21827538;hs1:21716185-21716438,hs1:23404798-23405060;hs1:21731611-21731948,hs1:51756592-51756960;hs1:21779175-21779530,hs1:26302121-26302507;hs1:21860789-21860982,hs1:22136113-22136368;hs1:21863664-21863797,hs1:23409466-23409615;hs1:21897106-21897375,hs1:26354197-26354531;hs1:21973522-21973860,hs1:22710232-22710583;hs1:21996421-21996694,hs1:26152722-26152869;hs1:22116364-22116687,hs1:23918444-23918787;hs1:22141346-22141679,hs1:52396944-52397259;hs1:22161823-22162027,hs1:23088466-23088742;hs1:22180392-22180688,hs1:52397602-52397963;hs1:22221837-22222175,hs1:24730665-24731006;hs1:22222455-22222829,hs1:234913416-234913816;hs1:22248892-22248988,hs1:23805313-23805665;hs1:22319716-22320059,hs1:22467593-22467956;hs1:22479726-22479996,hs1:22572433-22572785;hs1:22502950-22503130,hs1:26058246-26058425;hs1:22505267-22505501,hs1:22638223-22638500;hs1:22543814-22543948,hs1:25378240-25378398;hs1:22554224-22554496,hs1:26170154-26170436;hs1:22574084-22574287,hs1:52411966-52412198;hs1:22577194-22577380,hs1:26358343-26358648;hs1:22582330-22582523,hs1:25370066-25370433;hs1:22620339-22620569,hs1:25344531-25344885;hs1:22648195-22648422,hs1:26608899-26609115;hs1:22711367-22711672,hs1:24734535-24734843;hs1:22718245-22718475,hs1:51765728-51766018;hs1:22739905-22740251,hs1:23137038-23137374;hs1:22818697-22819009,hs1:24007975-24008300;hs1:22884645-22884855,hs1:25461263-25461502;hs1:22884860-22885000,hs1:25461511-25461624;hs1:22900546-22900794,hs1:25357360-25357485;hs1:23067796-23067978,hs1:23103508-23103856;hs1:23068179-23068508,hs1:23794761-23795102;hs1:23072988-23073330,hs1:23075935-23076271;hs1:23137054-23137384,hs1:26548912-26549270;hs1:23209386-23209625,hs1:52246333-52246581;hs1:23260096-23260444,hs1:23427830-23428218;hs1:23290351-23290523,hs1:23308574-23308735;hs1:23291741-23292066,hs1:23805921-23806262;hs1:23380386-23380697,hs1:23409547-23409878;hs1:23409103-23409411,hs1:24719218-24719564;hs1:23409341-23409454,hs1:24379500-24379622;hs1:23409423-23409553,hs1:23919677-23919806;hs1:23409429-23409525,hs1:23416869-23416997;hs1:23409478-23409635,hs1:23822124-23822294;hs1:23409544-23409832,hs1:25843485-25843790;hs1:23409561-23409882,hs1:24573508-24573816;hs1:23409587-23409769,hs1:24578484-24578690;hs1:23472703-23472841,hs1:23884628-23884776;hs1:23473863-23474240,hs1:23913838-23914197;hs1:23512431-23512657,hs1:23822037-23822279;hs1:23512517-23512643,hs1:25843470-25843706;hs1:23537867-23538116,hs1:51412755-51413019;hs1:23540367-23540750,hs1:26104188-26104537;hs1:23571940-23572182,hs1:23800598-23800825;hs1:23586579-23586946,hs1:51990117-51990525;hs1:23597421-23597648,hs1:26417898-26418131;hs1:23598604-23598854,hs1:24878784-24879085;hs1:23599035-23599365,hs1:24902335-24902677;hs1:23711156-23711516,hs1:51392137-51392496;hs1:23726910-23727288,hs1:52275990-52276322;hs1:23727817-23728135,hs1:26939992-26940530;hs1:23732151-23732456,hs1:26870436-26870741;hs1:23800641-23800952,hs1:24943527-24943830;hs1:23822113-23822314,hs1:25843482-25843757;hs1:23936010-23936278,hs1:24409053-24409412;hs1:23982802-23983129,hs1:25201958-25202255;hs1:24000779-24001120,hs1:24495854-24496200;hs1:24225387-24225532,hs1:24495613-24495777;hs1:24240035-24240296,hs1:24508363-24508645;hs1:24403830-24404089,hs1:25156460-25156734;hs1:24449227-24449578,hs1:24803941-24804252;hs1:24479053-24479142,hs1:24809277-24809386;hs1:24575567-24575944,hs1:26418942-26419323;hs1:24578097-24578319,hs1:51756725-51756884;hs1:24628036-24628342,hs1:26944739-26945081;hs1:24809744-24810121,hs1:25889227-25889620;hs1:24825388-24825717,hs1:24996810-24997149;hs1:24864673-24864989,hs1:52410307-52410618;hs1:24938707-24939066,hs1:26779803-26780152;hs1:24984792-24985101,hs1:26611081-26611450;hs1:24995679-24996085,hs1:26504745-26505133;hs1:25073349-25073674,hs1:25879299-25879604;hs1:25190746-25191105,hs1:26059767-26060116;hs1:25218270-25218560,hs1:25473335-25473618;hs1:25342625-25342960,hs1:25373257-25373592;hs1:25411537-25411848,hs1:26059849-26060140;hs1:25433958-25434314,hs1:25478540-25478887;hs1:25450207-25450470,hs1:25942927-25943082;hs1:25553118-25553503,hs1:26326659-26327055;hs1:25642898-25642986,hs1:25843688-25843798;hs1:25811458-25811801,hs1:51986374-51986743;hs1:25843492-25843742,hs1:52424396-52424672;hs1:25981781-25982158,hs1:26035841-26036222;hs1:25987723-25988044,hs1:26010943-26011291;hs1:26021817-26022016,hs1:26360528-26360869;hs1:26046453-26046665,hs1:26058242-26058418;hs1:26052244-26052473,hs1:52249071-52249342;hs1:26082879-26083129,hs1:26336153-26336433;hs1:26155862-26156231,hs1:26358057-26358425;hs1:26166451-26166832,hs1:26648421-26648791;hs1:26200742-26201128,hs1:26345394-26345790;hs1:26213943-26214257,hs1:26695674-26695999;hs1:26256174-26256295,hs1:26344120-26344341;hs1:26256573-26256929,hs1:26405339-26405700;hs1:26269228-26269577,hs1:26334311-26334677;hs1:26272866-26273048,hs1:26477827-26478149;hs1:26365905-26366242,hs1:26640569-26640908;hs1:26366742-26367084,hs1:26659108-26659427;hs1:26394864-26395172,hs1:26613952-26614323;hs1:26450628-26450969,hs1:26661536-26661917;hs1:26480709-26481023,hs1:26617760-26618059;hs1:26560488-26560808,hs1:52232195-52232524;hs1:26752023-26752378,hs1:52245898-52246205;hs1:26815830-26816112,hs1:26832146-26832496;hs1:26873345-26873697,hs1:26983163-26983509;hs1:26924631-26925021,hs1:52048474-52048851;hs1:26926028-26926399,hs1:27029723-27030065;hs1:26981588-26981939,hs1:51980264-51980628;hs1:27006156-27006523,hs1:52190873-52191189;hs1:27008289-27008616,hs1:52193454-52193792;hs1:27035373-27035712,hs1:51509156-51509516;hs1:27064526-27064893,hs1:90450616-90450986;hs1:27079259-27079610,hs1:51156552-51156930;hs1:27085781-27086073,hs1:90401563-90401885;hs1:51126401-51126663,hs1:51451683-51451936;hs1:51155839-51156134,hs6:123933147-123933475;hs1:51194674-51194870,hs1:51539886-51540141;hs1:51244750-51245108,hs1:52209065-52209404;hs1:51287867-51288225,hs1:51571928-51572293;hs1:51312246-51312604,hs1:51843611-51843989;hs1:51314114-51314484,hs1:51777655-51778048;hs1:51498901-51499113,hs1:52207345-52207595;hs1:51595392-51595771,hs1:52326356-52326775;hs1:51781800-51782157,hs1:51837401-51837726;hs1:51825966-51826326,hs1:51848243-51848575;hs1:51891796-51892135,hs1:51900259-51900563;hs1:51944716-51945080,hs1:51977525-51977875;hs1:51992459-51992824,hs1:52009335-52009718;hs1:51995937-51996282,hs1:52011322-52011692;hs1:52044507-52044901,hs1:52162910-52163272;hs1:52082719-52083065,hs1:52151277-52151641;hs1:52161695-52162064,hs1:90476184-90476606;hs1:52266530-52266649,hs1:52267771-52267854;hs1:52307780-52308057,hs1:52382770-52383034;hs1:90386341-90386705,hs6:123939894-123940272;hs1:90440841-90441211,hs1:90454669-90455042;hs1:248642878-248643001,hs1:248732078-248732201;hs2:31690107-31690380,hs2:159764285-159764605;hs2:32882232-32882577,hs2:161604168-161604502;hs2:33349580-33349686,hs2:34011346-34011452;hs2:34206068-34206315,hs2:161661205-161661450;hs2:34621942-34622265,hs2:34823249-34823576;hs2:104516270-104516578,hs2:162091520-162091824;hs2:105140246-105140472,hs2:162093057-162093279;hs2:160427503-160427688,hs2:161386442-161386700;hs3:149333920-149334015,hs3:168393277-168393359;hs4:95430901-95430983,hs4:99682612-99682700;hs6:123896796-123897109,hs6:123901906-123902324;hs7:66625939-66626030,hs7:72116544-72116622;hs7:81295894-81296198,hs7:87021036-87021372;hs7:81479507-81479869,hs7:85810348-85810505;hs7:81532688-81533000,hs7:86156907-86157263;hs7:85751548-85751797,hs7:86610684-86610963;hs7:85810848-85811116,hs7:86577559-86577916;hs8:50618665-50619062,hs9:107481422-107481532;hs9:21909748-21910123,hs9:32065057-32065422;hs9:26017659-26018028,hs9:26520502-26520858;hs9:32414274-32414645,hs9:32423764-32424136;hs9:32581769-32582131,hs9:32584974-32585366;hs11:11319161-11319550,hs9:24156122-24156497;hs11:11319719-11320052,hs11:11624452-11624808;hs11:11468241-11468589,hs11:11470941-11471281;hs11:11475867-11476225,hs11:11623580-11623945;hs11:13262241-13262392,hs7:107410598-107410679;hs11:18730124-18730205,hs9:107849978-107850119;hs11:28890178-28890511,hs11:30253695-30254030;hs11:28890998-28891213,hs11:29044637-29044866;hs11:29513402-29513756,hs11:33790915-33791235;hs11:29803524-29803779,hs11:30334128-30334467;hs11:30037004-30037275,hs11:30038226-30038519;hs11:30519412-30519642,hs11:33483937-33484169;hs11:38342038-38342314,hs11:126270221-126270544;hs11:80081255-80081616,hs11:80499726-80500074;hs12:16889304-16889668,hs12:16890562-16890902;hs12:17275022-17275354,hs12:17454495-17454800;hs13:52215669-52215745,hs5:103464448-103464569;hs14:25754105-25754487,hs14:25790068-25790450;hs16:5623427-5623641,hs16:20708241-20708464;hs16:5646637-5647008,hs16:7327390-7327756;hs16:5958553-5958633,hs16:20708795-20708889 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22903, USA Tumor genomes are generally thought to evolve through a gradual accumulation of mutations, but the observation that extraordinarily complex rearrangements can arise through single mutational events suggests that evolution may be accelerated by punctuated changes in genome architecture. To assess the prevalence and origins of complex genomic rearrangements (CGRs), we mapped 6179 somatic structural variation breakpoints in 64 cancer genomes from seven tumor types and screened for clusters of three or more interconnected breakpoints. We find that complex breakpoint clusters are extremely common: 154 clusters comprise 25% of all somatic breakpoints, and 75% of tumors exhibit at least one complex cluster. Based on copy number state profiling, 63% of breakpoint clusters are consistent with being CGRs that arose through a single mutational event. CGRs have diverse architectures including focal breakpoint clusters, large-scale rearrangements joining clusters from one or more chromosomes, and staggeringly complex chromothripsis events. Notably, chromothripsis has a significantly higher incidence in glioblastoma samples (39%) relative to other tumor types (9%). Chromothripsis breakpoints also show significantly elevated intra-tumor allele frequencies relative to simple SVs, which indicates that they arise early during tumorigenesis or confer selective advantage. Finally, assembly and analysis of 4002 somatic and 6982 germline breakpoint sequences reveal that somatic breakpoints show significantly less microhomology and fewer templated insertions than germline breakpoints, and this effect is stronger at CGRs than at simple variants. These results are inconsistent with replication-based models of CGR genesis and strongly argue that nonhomologous repair of concurrently arising DNA double-strand breaks is the predominant mechanism underlying complex cancer genome rearrangements. GRCh37/hg19 Yes NA CTDB0228 Research 23410887 Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA, Layer RM, Quinlan AR, Hall IM Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms Genome Research 2013 May 3 Glioblastoma Next Generation Sequencing Homo sapiens GBM_8_T Illumina paired-end sequencing chr1:16026777-16036777:-1;chr1:16337864-16347864:1;chr1:120102462-120112462:1;chr1:159464471-159474471:-1;chr1:160624058-160634058:1;chr1:203873394-203883394:-1;chr2:5159707-5169707:-1;chr2:110251448-110261448:-1;chr2:179388295-179398295:-1;chr2:193243388-193253388:1;chr2:193374282-193384282:-1;chr2:239782842-239792842:-1;chr2:240820510-240830510:-1;chr3:32662238-32672238:-1;chr3:50359495-50369495:1;chr3:93956283-93966283:-1;chr3:93981304-93991304:1;chr3:94225146-94235146:-1;chr3:96605898-96615898:-1;chr3:96837744-96847744:1;chr3:97011505-97021505:-1;chr3:97054254-97064254:1;chr3:97734321-97744321:-1;chr3:97759454-97769454:1;chr3:98144637-98154637:-1;chr3:98203181-98213181:1;chr3:98759057-98769057:-1;chr3:98964347-98974347:1;chr3:100414539-100424539:-1;chr3:100599940-100609940:-1;chr3:100682948-100692948:1;chr3:102385868-102395868:-1;chr3:102570358-102580358:1;chr3:102991747-103001747:-1;chr3:103108295-103118295:1;chr3:103139319-103149319:-1;chr3:103242865-103252865:1;chr3:104208716-104218716:-1;chr3:104264731-104274731:1;chr3:104411668-104421668:-1;chr3:104431668-104441668:1;chr3:104551867-104561867:-1;chr3:104597157-104607157:1;chr3:104682641-104692641:-1;chr3:104773233-104783233:1;chr3:105978496-105988496:-1;chr3:106226076-106236076:1;chr3:106267049-106277049:-1;chr3:106302185-106312185:1;chr3:106887417-106897417:-1;chr3:106942455-106952455:1;chr3:107321013-107331013:-1;chr3:107386184-107396184:1;chr3:108759695-108769695:-1;chr3:108835574-108845574:1;chr3:109043066-109053066:-1;chr3:109088880-109098880:1;chr3:109557183-109567183:-1;chr3:109665735-109675735:1;chr3:109800787-109810787:-1;chr3:109821117-109831117:1;chr3:109869164-109879164:-1;chr3:109941364-109951364:1;chr3:110084017-110094017:-1;chr3:110114017-110124017:1;chr3:110438023-110448023:-1;chr3:110621725-110631725:1;chr3:110696923-110706923:-1;chr3:110819832-110829832:1;chr3:111805202-111815202:-1;chr3:111860455-111870455:1;chr3:112208938-112218938:-1;chr3:112585484-112595484:1;chr3:112700900-112710900:-1;chr3:112944150-112954150:1;chr3:113087432-113097432:-1;chr3:113185905-113195905:1;chr3:132367950-132377950:-1;chr3:132433274-132443274:1;chr3:132527573-132537573:-1;chr3:132635317-132645317:1;chr3:132783700-132793700:-1;chr3:132871297-132881297:1;chr3:133643613-133653613:-1;chr3:133760958-133770958:1;chr3:134568031-134578031:-1;chr3:134653341-134663341:1;chr3:134991779-135001779:-1;chr3:135019751-135029751:1;chr3:137268337-137278337:-1;chr3:137328505-137338505:1;chr3:137383997-137393997:-1;chr3:137464535-137474535:1;chr3:138030477-138040477:1;chr3:140278516-140288516:-1;chr3:140328560-140338560:1;chr3:140388137-140398137:-1;chr3:140428239-140438239:1;chr3:142305590-142315590:-1;chr3:142361328-142371328:1;chr3:142894819-142904819:-1;chr3:142986057-142996057:1;chr3:143983667-143993667:-1;chr3:144038842-144048842:1;chr3:145913181-145923181:-1;chr3:145949196-145959196:1;chr3:147426214-147436214:-1;chr3:147519057-147529057:1;chr3:149868923-149878923:-1;chr3:149984748-149994748:1;chr3:150845589-150855589:-1;chr3:150886018-150896018:1;chr3:152234060-152244060:-1;chr3:152249180-152259180:1;chr3:152470244-152480244:-1;chr3:152541312-152551312:1;chr3:153890580-153900580:-1;chr3:154118590-154128590:1;chr3:157574792-157584792:-1;chr3:157804118-157814118:1;chr3:158099505-158109505:-1;chr3:158814997-158824997:-1;chr3:158887505-158897505:1;chr3:158958229-158968229:-1;chr3:158993432-159003432:1;chr3:160325148-160335148:-1;chr3:160345155-160355155:1;chr3:161308519-161318519:-1;chr3:161403919-161413919:1;chr3:161831437-161841437:-1;chr3:161967045-161977045:1;chr3:162213236-162223236:1;chr3:163329725-163339725:-1;chr3:163378406-163388406:1;chr3:163551758-163561758:-1;chr3:164017438-164027438:1;chr3:165141527-165151527:-1;chr3:165244781-165254781:1;chr3:165412133-165422133:-1;chr3:165532679-165542679:1;chr3:167073722-167083722:-1;chr3:167128857-167138857:1;chr3:168127998-168137998:-1;chr3:168148342-168158342:1;chr3:168795278-168805278:-1;chr3:168890649-168900649:1;chr3:169037140-169047140:1;chr3:169210544-169220544:1;chr3:172246981-172256981:-1;chr3:172302860-172312860:1;chr3:172387973-172397973:-1;chr3:172812308-172822308:1;chr3:172898972-172908972:-1;chr4:54367009-54377009:-1;chr4:54878429-54888429:1;chr4:55127836-55137836:-1;chr4:55270039-55280039:1;chr4:55290521-55300521:1;chr4:59792957-59802957:-1;chr4:167586041-167596041:-1;chr5:663946-673946:1;chr5:66575376-66585376:-1;chr5:66600376-66610376:1;chr5:71130528-71140528:-1;chr5:97579286-97589286:-1;chr5:126076043-126086043:1;chr5:139058717-139068717:-1;chr5:139447761-139457761:1;chr5:178883753-178893753:-1;chr5:179359253-179369253:1;chr6:3175533-3185533:-1;chr6:3705227-3715227:1;chr6:17684703-17694703:1;chr6:30204054-30214054:1;chr6:30223916-30233916:-1;chr6:38583221-38593221:1;chr6:47596472-47606472:1;chr6:47610244-47620244:-1;chr6:53302320-53312320:-1;chr6:68284842-68294842:1;chr6:99266469-99276469:1;chr6:99281469-99291469:-1;chr6:119213764-119223764:-1;chr6:157709391-157719391:-1;chr6:167934630-167944630:-1;chr7:5654010-5664010:-1;chr7:52334867-52344867:1;chr7:54715201-54725201:-1;chr7:55303258-55313258:1;chr7:61991316-62001316:1;chr7:64323527-64333527:-1;chr7:155117625-155127625:-1;chr8:11814605-11824605:-1;chr8:43599865-43609865:-1;chr8:144031199-144041199:-1;chr9:8376982-8386982:1;chr9:9804781-9814781:1;chr9:21686884-21696884:1;chr9:23223671-23233671:-1;chr9:23400330-23410330:1;chr9:24900120-24910120:-1;chr9:26658783-26668783:-1;chr9:127514564-127524564:1;chr9:127877286-127887286:-1;chr10:37491748-37501748:-1;chr10:89311765-89321765:1;chr10:90283938-90293938:-1;chr10:99243469-99253469:-1;chr10:99669279-99679279:1;chr11:3626990-3636990:-1;chr11:9291735-9301735:1;chr11:9591700-9601700:-1;chr11:51260568-51270568:1;chr11:64776977-64786977:-1;chr11:65681939-65691939:1;chr11:129910760-129920760:-1;chr12:155502-165502:-1;chr12:34836723-34846723:-1;chr12:38446681-38456681:1;chr12:56917346-56927346:-1;chr12:58160099-58170099:1;chr12:69104849-69114849:-1;chr12:69247313-69257313:-1;chr12:69380435-69390435:1;chr12:110952782-110962782:-1;chr12:122584226-122594226:-1;chr13:20222500-20232500:-1;chr13:26104583-26114583:1;chr13:46625166-46635166:-1;chr13:48478661-48488661:1;chr13:53193282-53203282:-1;chr13:81968195-81978195:-1;chr13:83692968-83702968:1;chr13:114448806-114458806:-1;chr14:21658252-21668252:-1;chr14:60770310-60780310:1;chr14:74970702-74980702:-1;chr14:76018053-76028053:1;chr14:76958337-76968337:-1;chr14:81329921-81339921:1;chr14:81651297-81661297:-1;chr14:82205690-82215690:1;chr14:85294257-85304257:-1;chr14:85319282-85329282:1;chr14:85653575-85663575:-1;chr14:85806600-85816600:1;chr14:86467181-86477181:-1;chr14:87361158-87371158:1;chr14:87507634-87517634:-1;chr14:88187857-88197857:1;chr14:88490221-88500221:-1;chr14:93583427-93593427:1;chr14:94082679-94092679:-1;chr14:102362762-102372762:1;chr14:107237686-107247686:-1;chr15:44164935-44174935:-1;chr15:44245191-44255191:1;chr16:35252178-35262178:-1;chr17:25954686-25964686:1;chr17:25979864-25989864:-1;chr18:14257101-14267101:-1;chr20:26082170-26092170:-1;chr21:10637520-10647520:-1;chr22:24676218-24686218:-1;chr22:25805798-25815798:1;chr22:25952284-25962284:1;chr22:41304674-41314674:-1;chr22:42399092-42409092:1;chr22:50776853-50786853:-1;chrX:25925646-25935646:-1;chrY:9949163-9959163:-1;chrY:28457355-28467355:-1;chrY:28769159-28779159:-1 hs1:16030303-16030399,hs22:41313865-41314010;hs1:17209330-17209576,hs22:42413054-42413323;hs3:16729648-16729750,hsY:21216904-21216982;hs3:93529236-93529320,hs3:97741289-97741439;hs3:94261103-94261172,hs3:104686427-104686598;hs3:96754624-96754737,hs3:108763485-108763696;hs3:96838818-96838990,hs3:132789533-132789669;hs3:97057561-97057690,hs3:172383538-172383715;hs3:97765003-97765168,hs3:112821447-112821590;hs3:98209306-98209435,hs3:100685094-100685254;hs3:98744889-98745026,hs3:102483425-102483555;hs3:98968643-98968781,hs3:158753928-158754113;hs3:100607201-100607342,hs3:167133105-167133210;hs3:102443442-102443628,hs3:110444308-110444480;hs3:103006204-103006343,hs3:133347968-133348098;hs3:103007764-103007904,hs3:103145282-103145433;hs3:103108530-103108732,hs3:172813916-172814064;hs3:103962782-103962880,hs3:165419362-165419467;hs3:104393474-104393644,hs3:111962567-111962696;hs3:104556948-104557122,hs3:107274939-107275113;hs3:105190181-105190290,hs3:163550160-163550254;hs3:106269690-106269801,hs3:169485207-169485298;hs3:106308916-106309027,hs3:132540196-132540385;hs3:106830690-106830937,hs3:107391896-107392119;hs3:106946254-106946401,hs3:135022426-135022517;hs3:107325443-107325642,hs3:140285478-140285583;hs3:109048260-109048381,hs3:110568252-110568416;hs3:109560258-109560375,hs3:158991840-158992063;hs3:109811707-109811904,hs3:132478757-132478907;hs3:110117257-110117398,hs3:137874749-137874942;hs3:110577401-110577597,hs3:167075361-167075509;hs3:111807299-111807496,hs3:167090462-167090636;hs3:112824107-112824299,hs3:113074519-113074602;hs3:113216744-113216852,hs3:172665201-172665288;hs3:132375267-132375353,hs3:132440410-132440506;hs3:132388171-132388293,hs3:172628942-172629058;hs3:132440656-132440757,hs3:169093719-169093837;hs3:132534505-132534602,hs3:150888708-150888932;hs3:132641891-132642038,hs3:168794115-168794208;hs3:132865176-132865286,hs3:161722229-161722367;hs3:132875631-132875750,hs3:137262270-137262442;hs3:133105722-133105926,hs3:158964856-158965014;hs3:133167866-133168049,hs3:133175263-133175474;hs3:133612540-133612752,hs3:165535671-165535817;hs3:134573236-134573401,hs3:149990174-149990332;hs3:134607355-134607452,hs3:157594178-157594329;hs3:135882602-135882762,hs3:163385627-163385759;hs3:135939104-135939243,hs3:172381541-172381788;hs3:136376214-136376312,hs3:158126366-158126536;hs3:136555275-136555446,hs3:138036806-138037012;hs3:137465990-137466152,hs3:142989005-142989189;hs3:138706223-138706434,hs3:167092439-167092539;hs3:140429682-140429800,hs3:142313607-142313781;hs3:140823999-140824194,hs3:152253690-152253897;hs3:145918717-145918893,hs3:169040924-169041076;hs3:147185491-147185623,hs3:172267390-172267591;hs3:154126160-154126372,hs3:169216167-169216307;hs3:158892400-158892564,hs3:164024135-164024340;hs3:160330903-160331034,hs3:161969458-161969677;hs3:160350027-160350199,hs3:161875879-161876093;hs3:162104782-162104904,hs3:172307472-172307610;hs3:162222694-162222831,hs3:168789224-168789417;hs3:172385248-172385343,hs3:172905774-172905878;hs3:172671317-172671521,hs3:172962642-172962755;hs4:54373632-54373851,hs4:55293702-55293946;hs4:54404467-54404592,hs4:54754982-54755229;hs4:54404762-54404915,hs4:54891898-54892051;hs4:54420180-54420311,hs4:54426608-54426820;hs4:54733622-54733850,hs4:55285168-55285384;hs5:139066019-139066212,hs5:179361553-179361727;hs5:139457143-139457313,hs5:178885623-178885785;hs7:41502567-41502826,hs7:42464348-42464578;hs7:54721974-54722147,hs7:54794860-54794947;hs7:54722093-54722213,hs7:55161785-55161937;hs7:54722561-54722762,hs7:55122638-55122739;hs7:54740309-54740480,hs7:55176651-55176800;hs7:54741383-54741615,hs7:55281628-55281890;hs7:54794737-54794844,hs7:55281931-55282019;hs7:54794855-54794947,hs7:55161734-55161936;hs7:54804542-54804754,hs7:55281933-55282019;hs7:54895510-54895631,hs7:55122662-55122739;hs7:54907941-54908100,hs7:55176556-55176641;hs7:55021423-55021653,hs7:55122877-55123101;hs7:55021938-55022061,hs7:55223150-55223347;hs7:55033541-55033648,hs7:55073918-55074034;hs7:55035866-55035972,hs7:55205341-55205520;hs7:55122389-55122634,hs7:55223386-55223564;hs7:55130498-55130765,hs7:55223085-55223314;hs7:55132228-55132441,hs7:55222615-55222792;hs7:55176556-55176637,hs7:55282048-55282161;hs7:55195488-55195698,hs7:55222220-55222438;hs7:55268726-55268960,hs7:55274292-55274537;hs7:62730499-62730605,hs7:62936641-62936739;hs9:9039856-9039952,hs9:12885172-12885333;hs9:21691885-21692022,hs9:27155594-27155692;hs9:23227129-23227359,hs9:27155320-27155470;hs12:69109975-69110218,hs12:69386190-69386333;hs13:25605969-25606139,hs6:53313910-53314107;hs13:25605998-25606143,hs14:99428142-99428324;hs13:26108762-26108929,hs14:95158155-95158353;hs13:46634086-46634298,hs14:95157109-95157319;hs13:48500565-48500707,hs6:53314449-53314636;hs13:84701695-84701835,hs6:129158617-129158827;hs14:21670985-21671189,hs14:74974496-74974640;hs14:69791945-69792139,hs14:85813744-85813967;hs14:85300243-85300420,hs14:88495041-88495206;hs14:87245744-87245894,hs14:87844842-87844996;hsX:139334400-139334598,hsX:140057569-140057717 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22903, USA Tumor genomes are generally thought to evolve through a gradual accumulation of mutations, but the observation that extraordinarily complex rearrangements can arise through single mutational events suggests that evolution may be accelerated by punctuated changes in genome architecture. To assess the prevalence and origins of complex genomic rearrangements (CGRs), we mapped 6179 somatic structural variation breakpoints in 64 cancer genomes from seven tumor types and screened for clusters of three or more interconnected breakpoints. We find that complex breakpoint clusters are extremely common: 154 clusters comprise 25% of all somatic breakpoints, and 75% of tumors exhibit at least one complex cluster. Based on copy number state profiling, 63% of breakpoint clusters are consistent with being CGRs that arose through a single mutational event. CGRs have diverse architectures including focal breakpoint clusters, large-scale rearrangements joining clusters from one or more chromosomes, and staggeringly complex chromothripsis events. Notably, chromothripsis has a significantly higher incidence in glioblastoma samples (39%) relative to other tumor types (9%). Chromothripsis breakpoints also show significantly elevated intra-tumor allele frequencies relative to simple SVs, which indicates that they arise early during tumorigenesis or confer selective advantage. Finally, assembly and analysis of 4002 somatic and 6982 germline breakpoint sequences reveal that somatic breakpoints show significantly less microhomology and fewer templated insertions than germline breakpoints, and this effect is stronger at CGRs than at simple variants. These results are inconsistent with replication-based models of CGR genesis and strongly argue that nonhomologous repair of concurrently arising DNA double-strand breaks is the predominant mechanism underlying complex cancer genome rearrangements. GRCh37/hg19 Yes NA CTDB0229 Research 23410887 Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA, Layer RM, Quinlan AR, Hall IM Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms Genome Research 2013 May 9,12,21 Glioblastoma Next Generation Sequencing Homo sapiens GBM_9_T Illumina paired-end sequencing chr1:147783685-147793685:1;chr1:180189188-180199188:1;chr1:180204188-180214188:-1;chr2:132978550-132988550:-1;chr2:143154687-143164687:1;chr2:146874558-146884558:-1;chr2:239782842-239792842:-1;chr2:240820510-240830510:-1;chr3:13753079-13763079:1;chr3:13774319-13784319:-1;chr3:38635682-38645682:-1;chr3:38690804-38700804:1;chr3:111865461-111875461:1;chr3:111956240-111966240:-1;chr3:113454964-113464964:1;chr3:113608707-113618707:-1;chr3:188256512-188266512:1;chr3:188387084-188397084:-1;chr3:193129316-193139316:1;chr3:193150909-193160909:-1;chr3:193845764-193855764:1;chr3:193866021-193876021:-1;chr4:3433221-3443221:1;chr4:20386821-20396821:1;chr4:20577907-20587907:-1;chr4:23821860-23831860:1;chr4:24022577-24032577:-1;chr4:24274237-24284237:1;chr4:24455515-24465515:-1;chr4:59792957-59802957:-1;chr4:78083375-78093375:-1;chr4:167586041-167596041:-1;chr5:663946-673946:1;chr5:97579286-97589286:-1;chr5:151344936-151354936:1;chr5:171340862-171350862:1;chr5:171367104-171377104:-1;chr6:266754-276754:-1;chr6:13848308-13858308:1;chr6:13879758-13889758:-1;chr6:119213764-119223764:-1;chr6:157709391-157719391:-1;chr6:167934630-167944630:-1;chr7:1334772-1344772:-1;chr7:1462411-1472411:1;chr7:1542934-1552934:-1;chr7:1563387-1573387:1;chr7:1598617-1608617:-1;chr7:1915807-1925807:-1;chr7:5232273-5242273:-1;chr7:5654010-5664010:-1;chr7:7043160-7053160:-1;chr7:44410109-44420109:-1;chr7:44440157-44450157:1;chr7:55964053-55974053:-1;chr7:66317948-66327948:-1;chr7:89691813-89701813:1;chr7:97823042-97833042:1;chr7:97858288-97868288:-1;chr7:104933970-104943970:1;chr7:127755670-127765670:1;chr7:127776296-127786296:-1;chr7:155117625-155127625:-1;chr8:144031199-144041199:-1;chr9:21267120-21277120:1;chr9:21288295-21298295:-1;chr9:21389078-21399078:1;chr9:21640555-21650555:1;chr9:22051826-22061826:-1;chr9:22225109-22235109:-1;chr9:22514593-22524593:1;chr9:22584037-22594037:-1;chr9:22609332-22619332:1;chr9:23294659-23304659:-1;chr9:23376222-23386222:1;chr9:23420485-23430485:-1;chr9:23653442-23663442:1;chr9:24229330-24239330:-1;chr9:25468995-25478995:1;chr9:25980154-25990154:-1;chr9:27294915-27304915:1;chr9:27341810-27351810:-1;chr9:108460003-108470003:1;chr9:139137092-139147092:1;chr9:139273468-139283468:-1;chr9:139385702-139395702:1;chr9:139426023-139436023:-1;chr11:3626990-3636990:-1;chr11:79741982-79751982:1;chr11:80564250-80574250:-1;chr11:89850991-89860991:-1;chr12:155502-165502:-1;chr12:20888039-20898039:1;chr12:67547097-67557097:-1;chr12:67807034-67817034:1;chr12:68159573-68169573:1;chr12:68473740-68483740:1;chr12:68745818-68755818:-1;chr12:68791645-68801645:1;chr12:69022852-69032852:-1;chr12:69079600-69089600:1;chr12:69181023-69191023:-1;chr12:69339318-69349318:1;chr12:69477463-69487463:-1;chr12:69599204-69609204:1;chr12:69669934-69679934:-1;chr12:69732547-69742547:1;chr12:114543222-114553222:-1;chr12:122584226-122594226:-1;chr13:114448806-114458806:-1;chr14:80505462-80515462:-1;chr14:84987295-84997295:-1;chr14:92483798-92493798:1;chr14:92510498-92520498:-1;chr14:105594882-105604882:1;chr15:73616132-73626132:-1;chr15:73651137-73661137:1;chr16:628413-638413:-1;chr16:1469260-1479260:1;chr16:1504869-1514869:-1;chr16:26402273-26412273:1;chr17:472976-482976:-1;chr17:483565-493565:1;chr17:80178649-80188649:1;chr17:80193818-80203818:-1;chr21:10637520-10647520:-1;chr22:44723940-44733940:-1;chr22:44743983-44753983:1;chr22:50175693-50185693:-1;chr22:50689936-50699936:1;chrY:9458259-9468259:1;chrY:9519351-9529351:-1;chrY:9644399-9654399:1 hs3:188257651-188257872,hs3:188393998-188394263;hs4:20389666-20389915,hs4:23824005-23824238;hs4:20582784-20583075,hs4:24459108-24459408;hs4:23528245-23528479,hs4:24279174-24279434;hs4:45340767-45340893,hs4:45567554-45567714;hs9:21275793-21275978,hs9:21644900-21645126;hs9:21292849-21293090,hs9:21494754-21495052;hs9:21393744-21393945,hs9:22057421-22057582;hs9:21485781-21486028,hs9:24314378-24314587;hs9:22230593-22230829,hs9:26105667-26105879;hs9:22460985-22461161,hs9:23423524-23423701;hs9:22462340-22462588,hs9:26954266-26954522;hs9:22516924-22517199,hs9:23383739-23384043;hs9:22611758-22611912,hs9:27301103-27301397;hs9:23572510-23572693,hs9:27411818-27412026;hs9:23572685-23572972,hs9:25550536-25550790;hs9:23658644-23658896,hs9:26118209-26118481;hs9:24232873-24233163,hs9:24656454-24656648;hs9:25471276-25471476,hs9:26057747-26057967;hs9:25549461-25549754,hs9:26735608-26735925;hs9:25983638-25983905,hs9:26119534-26119803;hs9:26058018-26058296,hs9:26546235-26546544;hs9:26106062-26106316,hs9:27348591-27348870;hs9:26549731-26550006,hs9:26742169-26742450;hs9:26704088-26704315,hs9:27413097-27413379;hs9:26705270-26705446,hs9:26959147-26959316;hs10:89526875-89527113,hs10:90662939-90663209;hs10:89628629-89628761,hs10:90697124-90697357;hs11:79747979-79748169,hs11:79769455-79769741;hs11:79772925-79773148,hs11:80570256-80570495;hs12:67550990-67551263,hs12:67877738-67877977;hs12:67586171-67586318,hs12:69189604-69189753;hs12:67601117-67601325,hs12:68408414-68408594;hs12:67601574-67601733,hs12:67790335-67790607;hs12:67620791-67621052,hs12:67782857-67783102;hs12:67630723-67630908,hs12:69513392-69513624;hs12:67633794-67634016,hs12:69218807-69218945;hs12:67680661-67680816,hs12:69588085-69588293;hs12:67690990-67691105,hs12:68774263-68774405;hs12:67691290-67691413,hs12:68781029-68781261;hs12:67705427-67705714,hs12:68076102-68076361;hs12:67730375-67730641,hs12:68771687-68771892;hs12:67739086-67739350,hs12:69267882-69268144;hs12:67764125-67764364,hs12:69291025-69291249;hs12:67782148-67782256,hs12:68750123-68750252;hs12:67787062-67787225,hs12:69779423-69779688;hs12:67788218-67788364,hs12:68394711-68394935;hs12:67956652-67956907,hs12:69778843-69779122;hs12:68074161-68074364,hs12:69293273-69293418;hs12:68114110-68114332,hs12:68125971-68126169;hs12:68364318-68364562,hs12:69737286-69737549;hs12:68397680-68397973,hs12:69518660-69518966;hs12:68400670-68400971,hs12:68468351-68468677;hs12:68400898-68401112,hs12:69247552-69247812;hs12:68405621-68405799,hs12:69274676-69274874;hs12:68411735-68411984,hs12:69588135-69588263;hs12:68414244-68414440,hs12:68786506-68786728;hs12:68414563-68414803,hs12:68431646-68431908;hs12:68414760-68414987,hs12:69589338-69589552;hs12:68419265-68419506,hs12:69284604-69284849;hs12:68446249-68446568,hs12:69294591-69294882;hs12:68447716-68448000,hs12:69293815-69294086;hs12:68452281-68452432,hs12:69574094-69574243;hs12:68787746-68788007,hs12:69557978-69558272;hs12:69034926-69035197,hs12:69557216-69557454;hs12:69077159-69077342,hs12:69242488-69242711;hs12:69186676-69187000,hs9:136844617-136844732;hs12:69189483-69189766,hs12:69562670-69562954;hs12:69310382-69310538,hs12:69325596-69325773;hs12:69532552-69532772,hs12:69694024-69694330;hs12:79278843-79279073,hs12:79279848-79280124;hs15:25355938-25356084,hs15:68741305-68741554;hs15:26166197-26166406,hs15:99358093-99358295;hs18:6746356-6746525,hs18:9355191-9355390;hs18:24963417-24963617,hs18:24964937-24965169;hs18:25735752-25736007,hs18:27396635-27396835 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22903, USA Tumor genomes are generally thought to evolve through a gradual accumulation of mutations, but the observation that extraordinarily complex rearrangements can arise through single mutational events suggests that evolution may be accelerated by punctuated changes in genome architecture. To assess the prevalence and origins of complex genomic rearrangements (CGRs), we mapped 6179 somatic structural variation breakpoints in 64 cancer genomes from seven tumor types and screened for clusters of three or more interconnected breakpoints. We find that complex breakpoint clusters are extremely common: 154 clusters comprise 25% of all somatic breakpoints, and 75% of tumors exhibit at least one complex cluster. Based on copy number state profiling, 63% of breakpoint clusters are consistent with being CGRs that arose through a single mutational event. CGRs have diverse architectures including focal breakpoint clusters, large-scale rearrangements joining clusters from one or more chromosomes, and staggeringly complex chromothripsis events. Notably, chromothripsis has a significantly higher incidence in glioblastoma samples (39%) relative to other tumor types (9%). Chromothripsis breakpoints also show significantly elevated intra-tumor allele frequencies relative to simple SVs, which indicates that they arise early during tumorigenesis or confer selective advantage. Finally, assembly and analysis of 4002 somatic and 6982 germline breakpoint sequences reveal that somatic breakpoints show significantly less microhomology and fewer templated insertions than germline breakpoints, and this effect is stronger at CGRs than at simple variants. These results are inconsistent with replication-based models of CGR genesis and strongly argue that nonhomologous repair of concurrently arising DNA double-strand breaks is the predominant mechanism underlying complex cancer genome rearrangements. GRCh37/hg19 Yes NA CTDB0230 Research 23410887 Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA, Layer RM, Quinlan AR, Hall IM Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms Genome Research 2013 May 7,20 Glioblastoma Next Generation Sequencing Homo sapiens GBM_10_T Illumina paired-end sequencing chr1:15463796-15473796:-1;chr1:16087782-16097782:1;chr1:37565238-37575238:-1;chr1:37951289-37961289:1;chr1:38013271-38023271:-1;chr1:38144498-38154498:1;chr1:104088495-104098495:-1;chr1:115439999-115449999:1;chr1:120102462-120112462:1;chr2:5159707-5169707:-1;chr2:75420018-75430018:1;chr2:75494525-75504525:-1;chr2:89128108-89138108:-1;chr2:239782842-239792842:-1;chr2:240820510-240830510:-1;chr3:195752783-195762783:-1;chr4:28449053-28459053:1;chr4:28757412-28767412:-1;chr4:49634410-49644410:-1;chr4:59792957-59802957:-1;chr4:81922393-81932393:1;chr4:82180675-82190675:-1;chr4:105401709-105411709:1;chr4:106611187-106621187:-1;chr4:107480514-107490514:-1;chr4:107496455-107506455:1;chr4:113699460-113709460:1;chr4:114752477-114762477:-1;chr4:167586041-167596041:-1;chr4:179382464-179392464:1;chr4:180112836-180122836:-1;chr4:190184009-190194009:-1;chr4:190194203-190204203:1;chr5:71130528-71140528:-1;chr5:97579286-97589286:-1;chr5:104502308-104512308:1;chr5:104537169-104547169:-1;chr5:134250526-134260526:-1;chr5:134261166-134271166:1;chr5:164958018-164968018:1;chr5:164978148-164988148:-1;chr5:165018420-165028420:1;chr5:166494607-166504607:-1;chr5:166839906-166849906:1;chr5:174898085-174908085:1;chr5:174923556-174933556:-1;chr5:178920131-178930131:1;chr5:178955446-178965446:-1;chr6:119213764-119223764:-1;chr6:167934630-167944630:-1;chr7:54772075-54782075:-1;chr7:55308258-55318258:1;chr7:64057937-64067937:-1;chr7:151490490-151500490:-1;chr7:151596629-151606629:1;chr7:151713609-151723609:1;chr7:154749730-154759730:1;chr7:155117625-155127625:-1;chr7:155404970-155414970:-1;chr7:155470863-155480863:1;chr7:155579518-155589518:-1;chr8:144031199-144041199:-1;chr9:18353170-18363170:1;chr9:21122146-21132146:1;chr9:24488040-24498040:-1;chr9:27208016-27218016:-1;chr11:15601337-15611337:-1;chr11:16333209-16343209:1;chr11:48956302-48966302:1;chr12:155502-165502:-1;chr12:2812474-2822474:-1;chr12:12372496-12382496:1;chr12:12526446-12536446:-1;chr12:38173235-38183235:1;chr12:81462149-81472149:-1;chr12:108398305-108408305:1;chr12:122584226-122594226:-1;chr13:66913552-66923552:-1;chr13:114448806-114458806:-1;chr14:20541384-20551384:1;chr14:20553240-20563240:-1;chr16:28479802-28489802:-1;chr16:87948522-87958522:-1;chr19:2126613-2136613:-1;chr19:2579171-2589171:1;chr19:15433639-15443639:1;chr19:15443866-15453866:-1;chr20:7483369-7493369:1;chr20:7849854-7859854:-1;chr20:10000146-10010146:1;chr20:10020725-10030725:-1;chr20:10147968-10157968:1;chr20:10527557-10537557:-1;chr20:14430451-14440451:1;chr20:14450088-14460088:-1;chr20:34954187-34964187:-1;chr20:52816363-52826363:-1;chr21:10637520-10647520:-1;chr22:50776853-50786853:-1;chrX:118644507-118654507:-1;chrX:118654877-118664877:1;chrX:127369756-127379756:-1;chrY:15994871-16004871:1;chrY:16079200-16089200:-1;chrY:23647227-23657227:1;chrY:23748666-23758666:-1;chrY:28457355-28467355:-1;chrY:77458284-77468284:-1 hs1:15471020-15471135,hs20:52823000-52823146;hs1:45566619-45566844,hs6:87238326-87238396;hs1:56801753-56801811,hs16:85156219-85156265;hs1:120221247-120221318,hs2:130906766-130906987;hs4:17393815-17394078,hsX:53237945-53238014;hs4:28761499-28761685,hs4:28797388-28797553;hs4:82051015-82051178,hs4:82182814-82182916;hs4:82063773-82063874,hs4:105404940-105405052;hs4:82096701-82096790,hs4:105404954-105405056;hs4:113707566-113707748,hs4:114757573-114757813;hs4:180108938-180109021,hs4:180113837-180114112;hs5:164905564-164905677,hs5:165022361-165022460;hs5:174902726-174902991,hs5:174928546-174928773;hs6:68909698-68909748,hs9:101560727-101560796;hs7:41008361-41008558,hs7:41009008-41009259;hs7:54776605-54776814,hs7:55314446-55314690;hs7:54802834-54802958,hs7:55075327-55075473;hs7:54835064-54835185,hs7:54862014-54862229;hs7:54874826-54875049,hs7:54882410-54882525;hs7:54888182-54888360,hs7:55278805-55279035;hs7:54911240-54911344,hs7:54915760-54915933;hs7:54927349-54927607,hs7:55076010-55076285;hs7:54968445-54968692,hs7:55240950-55241203;hs7:54968766-54968943,hs7:55241304-55241534;hs7:54971109-54971231,hs7:55070613-55070733;hs7:55011430-55011535,hs7:55019742-55019868;hs7:55036491-55036712,hs7:55103207-55103452;hs7:55102899-55103026,hs7:55223218-55223379;hs7:55194031-55194157,hs7:55222048-55222265;hs7:55209570-55209838,hs7:55223464-55223748;hs7:150314480-150314640,hs7:151582417-151582645;hs7:150420079-150420204,hs7:151434716-151434963;hs7:151439895-151440011,hs7:151601368-151601505;hs7:151495821-151496048,hs7:151603027-151603232;hs7:151577493-151577733,hs7:151594688-151594941;hs7:151584022-151584253,hs7:151601720-151601819;hs7:154751221-154751402,hs7:155128712-155128948;hs7:154783139-154783323,hs7:154807210-154807463;hs7:154805745-154805877,hs7:155580617-155580776;hs7:154806472-154806663,hs7:155412342-155412456;hs7:155094402-155094626,hs7:155411165-155411394;hs7:155412336-155412406,hs7:155481146-155481221;hs8:77957237-77957297,hs8:78003437-78003497;hs9:18358406-18358592,hs9:27213453-27213608;hs9:21130169-21130357,hs9:24494259-24494429;hs9:24584121-24584290,hs9:24590638-24590843;hs12:25718373-25718423,hs12:25749632-25749867;hs16:20940071-20940122,hs6:29853122-29853216;hs18:14387933-14387999,hs2:86282474-86282699;hs18:74793571-74793644,hs6:142519220-142519279;hs19:2132304-2132497,hs19:2602419-2602665;hs19:19924778-19924833,hs19:20466062-20466165;hs20:7485256-7485480,hs7:151603232-151603409;hs20:7485294-7485483,hs20:7568756-7568831;hs20:7485307-7485519,hs20:7858926-7859088;hs20:7567604-7567816,hs7:151602268-151602441;hs20:7858552-7858801,hs7:151603149-151603394;hs20:7859740-7859930,hs7:151603494-151603632;hs20:10023614-10023851,hs20:10538626-10538877;hs20:10533315-10533448,hs7:151439697-151439817;hs20:10539191-10539393,hs7:151598544-151598720 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22903, USA Tumor genomes are generally thought to evolve through a gradual accumulation of mutations, but the observation that extraordinarily complex rearrangements can arise through single mutational events suggests that evolution may be accelerated by punctuated changes in genome architecture. To assess the prevalence and origins of complex genomic rearrangements (CGRs), we mapped 6179 somatic structural variation breakpoints in 64 cancer genomes from seven tumor types and screened for clusters of three or more interconnected breakpoints. We find that complex breakpoint clusters are extremely common: 154 clusters comprise 25% of all somatic breakpoints, and 75% of tumors exhibit at least one complex cluster. Based on copy number state profiling, 63% of breakpoint clusters are consistent with being CGRs that arose through a single mutational event. CGRs have diverse architectures including focal breakpoint clusters, large-scale rearrangements joining clusters from one or more chromosomes, and staggeringly complex chromothripsis events. Notably, chromothripsis has a significantly higher incidence in glioblastoma samples (39%) relative to other tumor types (9%). Chromothripsis breakpoints also show significantly elevated intra-tumor allele frequencies relative to simple SVs, which indicates that they arise early during tumorigenesis or confer selective advantage. Finally, assembly and analysis of 4002 somatic and 6982 germline breakpoint sequences reveal that somatic breakpoints show significantly less microhomology and fewer templated insertions than germline breakpoints, and this effect is stronger at CGRs than at simple variants. These results are inconsistent with replication-based models of CGR genesis and strongly argue that nonhomologous repair of concurrently arising DNA double-strand breaks is the predominant mechanism underlying complex cancer genome rearrangements. GRCh37/hg19 Yes NA CTDB0231 Research 23410887 Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA, Layer RM, Quinlan AR, Hall IM Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms Genome Research 2013 May 1 Glioblastoma Next Generation Sequencing Homo sapiens GBM_13_T Illumina paired-end sequencing chr1:1473900-1483900:-1;chr1:1551635-1561635:1;chr1:3449021-3459021:-1;chr1:3550481-3560481:1;chr1:5100041-5110041:1;chr1:5119899-5129899:-1;chr1:6305284-6315284:-1;chr1:6392746-6402746:1;chr1:6643789-6653789:1;chr1:6684084-6694084:-1;chr1:7510842-7520842:1;chr1:7808228-7818228:1;chr1:7823416-7833416:-1;chr1:7940209-7950209:1;chr1:8404605-8414605:-1;chr1:8659571-8669571:1;chr1:8776326-8786326:-1;chr1:29104029-29114029:1;chr1:29164947-29174947:-1;chr1:29533361-29543361:1;chr1:31320068-31330068:-1;chr1:32889919-32899919:1;chr1:32913996-32923996:-1;chr1:35689182-35699182:1;chr1:35913488-35923488:-1;chr1:35964642-35974642:1;chr1:36015190-36025190:-1;chr1:36035190-36045190:1;chr1:36738433-36748433:-1;chr1:104078440-104088440:-1;chr1:104302999-104312999:-1;chr2:110251448-110261448:-1;chr2:133112726-133122726:1;chr2:239782842-239792842:-1;chr2:240820510-240830510:-1;chr3:26418714-26428714:1;chr3:26440642-26450642:-1;chr3:75633940-75643940:-1;chr4:32843693-32853693:-1;chr4:59792957-59802957:-1;chr4:167586041-167596041:-1;chr5:71130528-71140528:-1;chr5:97579286-97589286:-1;chr6:119208764-119218764:-1;chr6:121356779-121366779:1;chr6:121368492-121378492:-1;chr6:157709391-157719391:-1;chr6:167934630-167944630:-1;chr7:1462411-1472411:1;chr7:1598617-1608617:-1;chr7:5795557-5805557:1;chr7:17311561-17321561:-1;chr7:17381954-17391954:1;chr7:24632043-24642043:-1;chr7:24708535-24718535:1;chr7:37681722-37691722:1;chr7:37829380-37839380:-1;chr7:44101536-44111536:-1;chr7:44259616-44269616:1;chr7:44279616-44289616:-1;chr7:46277990-46287990:1;chr7:46538429-46548429:-1;chr7:46835589-46845589:1;chr7:46860185-46870185:-1;chr7:47338918-47348918:-1;chr7:48229521-48239521:-1;chr7:48240125-48250125:-1;chr7:54720253-54730253:-1;chr7:55470927-55480927:1;chr7:58026538-58036538:1;chr7:63420797-63430797:-1;chr7:82371999-82381999:-1;chr7:87480469-87490469:1;chr7:97676376-97686376:-1;chr7:105245683-105255683:-1;chr7:107104811-107114811:-1;chr7:107124869-107134869:1;chr7:108966633-108976633:-1;chr7:109154192-109164192:1;chr7:109716189-109726189:1;chr7:116966422-116976422:-1;chr7:117057200-117067200:1;chr7:117154148-117164148:-1;chr7:117279506-117289506:1;chr7:117979873-117989873:-1;chr7:120212430-120222430:1;chr7:124971074-124981074:-1;chr7:125563328-125573328:-1;chr7:125908056-125918056:1;chr7:134718723-134728723:-1;chr7:134744068-134754068:1;chr7:142181863-142191863:-1;chr7:148721779-148731779:1;chr7:148939448-148949448:-1;chr7:149462471-149472471:1;chr7:149522848-149532848:-1;chr7:155117625-155127625:-1;chr8:16279220-16289220:1;chr8:32686630-32696630:-1;chr8:118188271-118198271:1;chr8:118228745-118238745:-1;chr8:144031199-144041199:-1;chr9:5038685-5048685:1;chr9:5079758-5089758:-1;chr9:5924441-5934441:1;chr9:5962458-5972458:-1;chr9:8961291-8971291:1;chr9:12713364-12723364:-1;chr9:13137514-13147514:1;chr9:13242749-13252749:-1;chr9:14603432-14613432:1;chr9:14681933-14691933:-1;chr9:15615226-15625226:1;chr9:15975329-15985329:-1;chr9:19505692-19515692:1;chr9:22412620-22422620:1;chr9:23400330-23410330:-1;chr9:23531978-23541978:-1;chr9:24395430-24405430:1;chr9:25660339-25670339:-1;chr9:28445744-28455744:1;chr9:31454589-31464589:-1;chr9:136110676-136120676:-1;chr10:31573788-31583788:1;chr10:31790278-31800278:-1;chr10:32088852-32098852:1;chr10:32139068-32149068:-1;chr10:37410938-37420938:1;chr10:37528393-37538393:-1;chr10:37611471-37621471:1;chr10:37657405-37667405:-1;chr11:49521210-49531210:1;chr11:49712975-49722975:-1;chr12:155502-165502:-1;chr12:10553933-10563933:1;chr12:52911054-52921054:-1;chr12:52941275-52951275:1;chr12:122584226-122594226:-1;chr13:41967871-41977871:1;chr13:114448806-114458806:-1;chr15:102423383-102433383:1;chr16:52187648-52197648:-1;chr18:14776372-14786372:1;chr18:14899878-14909878:-1;chr18:40587348-40597348:-1;chr19:1292451-1302451:-1;chr19:11800006-11810006:1;chr19:22325082-22335082:1;chr20:29543855-29553855:-1;chr20:31265235-31275235:1;chr20:58413300-58423300:-1;chr20:58501073-58511073:1;chr20:60874673-60884673:1;chr21:9523596-9533596:-1;chr21:9998622-10008622:1;chr21:10637520-10647520:-1;chr21:11048456-11058456:-1;chr21:11135793-11145793:1;chr22:42018682-42028682:1;chrX:115145778-115155778:-1;chrY:7983379-7993379:-1;chrY:19369648-19379648:1;chrY:19400376-19410376:-1 hs1:3454237-3454412,hs1:8511349-8511599;hs1:6303332-6303446,hs1:8662465-8662702;hs1:6396205-6396311,hs1:8689355-8689488;hs1:7515413-7515532,hs1:8683090-8683238;hs1:7517175-7517317,hs1:8781980-8782132;hs1:7813832-7814013,hs1:8504093-8504366;hs1:8662134-8662267,hs1:8700311-8700464;hs1:8662450-8662595,hs1:8700382-8700601;hs1:8663190-8663299,hs1:8708867-8709022;hs1:8663761-8663882,hs1:35971087-35971297;hs1:8664123-8664237,hs1:29579822-29579944;hs1:8699913-8700065,hs1:35940156-35940291;hs1:29170571-29170685,hs1:35969711-35969815;hs1:29535725-29535945,hs1:36867509-36867730;hs1:31804836-31804997,hs1:36742016-36742126;hs1:31808516-31808702,hs1:35920291-35920469;hs1:31867117-31867365,hs1:36741388-36741637;hs3:47233651-47233938,hs3:47257174-47257381;hs7:37589962-37590121,hs7:53510290-53510465;hs7:37686332-37686537,hs7:55752931-55753126;hs7:38394024-38394378,hs7:38402927-38403379;hs7:44064642-44064822,hs7:55477492-55477665;hs7:44105644-44105860,hs7:46668999-46669220;hs7:44473274-44473418,hs7:45367940-45368109;hs7:44474324-44474506,hs7:45368850-45369038;hs7:44663348-44663508,hs7:45093900-45094041;hs7:46281318-46281553,hs7:46858826-46859061;hs7:46539953-46540168,hs7:56843775-56843993;hs7:46668304-46668506,hs7:52510293-52510439;hs7:46686462-46686695,hs7:50572984-50573229;hs7:47183843-47184023,hs7:53509865-53510090;hs7:50988387-50988638,hs7:56515008-56515228;hs7:51498444-51498643,hs7:55748688-55748869;hs7:52511527-52511673,hs7:54723314-54723440;hs7:53065290-53065450,hs7:53066624-53066842;hs7:55743359-55743592,hs7:55744494-55744674;hs7:56694798-56694964,hs7:56842829-56843003;hs7:57276359-57276589,hs7:57276960-57277075;hs7:57724224-57724369,hs7:57869932-57870050;hs8:118191193-118191309,hs8:118316071-118316225;hs8:118230469-118230683,hs8:118323094-118323275;hs8:146297665-146297787,hs8:146303103-146303235;hs15:24361810-24361904,hs15:24524974-24525096;hs15:71021993-71022138,hs6:155950340-155950480;hs19:11797085-11797289,hs19:11800014-11800201 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22903, USA Tumor genomes are generally thought to evolve through a gradual accumulation of mutations, but the observation that extraordinarily complex rearrangements can arise through single mutational events suggests that evolution may be accelerated by punctuated changes in genome architecture. To assess the prevalence and origins of complex genomic rearrangements (CGRs), we mapped 6179 somatic structural variation breakpoints in 64 cancer genomes from seven tumor types and screened for clusters of three or more interconnected breakpoints. We find that complex breakpoint clusters are extremely common: 154 clusters comprise 25% of all somatic breakpoints, and 75% of tumors exhibit at least one complex cluster. Based on copy number state profiling, 63% of breakpoint clusters are consistent with being CGRs that arose through a single mutational event. CGRs have diverse architectures including focal breakpoint clusters, large-scale rearrangements joining clusters from one or more chromosomes, and staggeringly complex chromothripsis events. Notably, chromothripsis has a significantly higher incidence in glioblastoma samples (39%) relative to other tumor types (9%). Chromothripsis breakpoints also show significantly elevated intra-tumor allele frequencies relative to simple SVs, which indicates that they arise early during tumorigenesis or confer selective advantage. Finally, assembly and analysis of 4002 somatic and 6982 germline breakpoint sequences reveal that somatic breakpoints show significantly less microhomology and fewer templated insertions than germline breakpoints, and this effect is stronger at CGRs than at simple variants. These results are inconsistent with replication-based models of CGR genesis and strongly argue that nonhomologous repair of concurrently arising DNA double-strand breaks is the predominant mechanism underlying complex cancer genome rearrangements. GRCh37/hg19 Yes NA CTDB0232 Research 23410887 Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA, Layer RM, Quinlan AR, Hall IM Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms Genome Research 2013 May 2,3,9,10 Glioblastoma Next Generation Sequencing Homo sapiens GBM_16_T Illumina paired-end sequencing chr1:2354953-2364953:1;chr1:2488566-2498566:-1;chr1:3373066-3383066:1;chr1:3525417-3535417:-1;chr1:8756113-8766113:-1;chr1:9155983-9165983:1;chr1:26060504-26070504:-1;chr1:26080609-26090609:1;chr1:37827296-37837296:1;chr1:37845289-37855289:-1;chr1:53128976-53138976:-1;chr1:53553994-53563994:1;chr1:104088495-104098495:-1;chr1:113372689-113382689:-1;chr1:191020292-191030292:1;chr1:191089707-191099707:-1;chr1:199315848-199325848:1;chr1:199424289-199434289:-1;chr1:204255393-204265393:-1;chr1:204564030-204574030:1;chr1:204971336-204981336:1;chr1:205067107-205077107:-1;chr1:205174084-205184084:-1;chr1:205447688-205457688:1;chr1:241741270-241751270:-1;chr2:97851959-97861959:-1;chr2:110251448-110261448:-1;chr2:212877226-212887226:1;chr2:239002055-239012055:1;chr2:239067730-239077730:-1;chr2:239782842-239792842:-1;chr2:240820510-240830510:-1;chr3:49149108-49159108:-1;chr3:49414617-49424617:1;chr3:183621218-183631218:1;chr3:183651744-183661744:-1;chr3:183693230-183703230:1;chr3:183713462-183723462:-1;chr3:183902649-183912649:1;chr3:183943657-183953657:-1;chr4:9232732-9242732:-1;chr4:59792957-59802957:-1;chr4:68128286-68138286:1;chr4:69541180-69551180:-1;chr4:132687808-132697808:1;chr4:167586041-167596041:-1;chr5:71130528-71140528:-1;chr5:97579286-97589286:-1;chr5:123968850-123978850:-1;chr5:124368193-124378193:1;chr5:135121725-135131725:-1;chr6:19032877-19042877:1;chr6:19047967-19057967:-1;chr6:47596472-47606472:1;chr6:47610244-47620244:-1;chr6:115272553-115282553:-1;chr6:119208764-119218764:-1;chr6:150256643-150266643:1;chr6:157709391-157719391:-1;chr6:167934630-167944630:-1;chr7:917429-927429:1;chr7:1462411-1472411:1;chr7:1542934-1552934:-1;chr7:1563387-1573387:1;chr7:1598617-1608617:-1;chr7:1993209-2003209:-1;chr7:2219477-2229477:-1;chr7:2506126-2516126:1;chr7:2663158-2673158:1;chr7:2737626-2747626:-1;chr7:4810785-4820785:1;chr7:4872109-4882109:-1;chr7:5222098-5232098:-1;chr7:5643860-5653860:-1;chr7:32808272-32818272:-1;chr7:33101282-33111282:1;chr7:35619459-35629459:-1;chr7:52833438-52843438:-1;chr7:53393785-53403785:-1;chr7:54477687-54487687:1;chr7:55281047-55291047:1;chr7:56913110-56923110:1;chr7:64514540-64524540:1;chr7:86862134-86872134:1;chr7:139493115-139503115:-1;chr7:139870422-139880422:1;chr7:149462471-149472471:1;chr7:149522848-149532848:-1;chr7:155117625-155127625:-1;chr8:9049806-9059806:1;chr8:9059885-9069885:-1;chr8:144031199-144041199:-1;chr8:145803185-145813185:-1;chr9:17880957-17890957:1;chr9:17953899-17963899:-1;chr9:18016176-18026176:1;chr9:18052794-18062794:-1;chr9:18133305-18143305:1;chr9:18183384-18193384:-1;chr9:18260405-18270405:1;chr9:18338170-18348170:-1;chr9:18353170-18363170:1;chr9:21878937-21888937:1;chr9:22067070-22077070:1;chr9:22681750-22691750:-1;chr9:34187903-34197903:-1;chr9:34241078-34251078:1;chr9:34942013-34952013:-1;chr9:36129248-36139248:1;chr9:138317356-138327356:1;chr9:139831461-139841461:1;chr9:140123170-140133170:-1;chr10:25088099-25098099:-1;chr10:25103376-25113376:1;chr10:26060380-26070380:-1;chr10:26131006-26141006:1;chr10:26172277-26182277:-1;chr10:26294884-26304884:1;chr10:26522187-26532187:-1;chr10:26791820-26801820:1;chr10:27183994-27193994:-1;chr10:27744376-27754376:1;chr10:27953921-27963921:-1;chr10:28673927-28683927:1;chr10:37485221-37495221:-1;chr11:388007-398007:1;chr11:414941-424941:-1;chr11:22512827-22522827:1;chr11:22598729-22608729:-1;chr11:67373802-67383802:1;chr12:155502-165502:-1;chr12:132305490-132315490:1;chr13:66913552-66923552:-1;chr13:100990944-101000944:-1;chr13:101436045-101446045:1;chr13:114448806-114458806:-1;chr14:39084534-39094534:-1;chr14:77177990-77187990:-1;chr14:77445776-77455776:1;chr14:104543384-104553384:1;chr14:104654090-104664090:-1;chr15:29824310-29834310:1;chr15:35415407-35425407:-1;chr15:35466166-35476166:1;chr15:50721384-50731384:-1;chr15:91186798-91196798:-1;chr15:91643788-91653788:1;chr16:304346-314346:1;chr16:349783-359783:-1;chr16:488491-498491:1;chr16:849127-859127:-1;chr16:1014450-1024450:1;chr16:51963859-51973859:1;chr16:52043194-52053194:-1;chr16:84524165-84534165:-1;chr16:84913925-84923925:1;chr16:88470192-88480192:1;chr16:88718417-88728417:-1;chr16:88758801-88768801:1;chr16:89136346-89146346:-1;chr16:89213215-89223215:1;chr16:89270988-89280988:-1;chr16:89685017-89695017:-1;chr17:21497908-21507908:-1;chr17:34050036-34060036:-1;chr17:34131752-34141752:1;chr17:41283112-41293112:1;chr17:41612981-41622981:-1;chr17:41846365-41856365:1;chr17:64041851-64051851:-1;chr17:64479464-64489464:1;chr17:66056863-66066863:1;chr17:66073850-66083850:-1;chr17:77071345-77081345:1;chr17:77151812-77161812:-1;chr17:77693713-77703713:-1;chr19:41669886-41679886:-1;chr19:42745266-42755266:1;chr19:42800952-42810952:-1;chr19:57997414-58007414:1;chr19:58025636-58035636:-1;chr21:10637520-10647520:-1;chr21:18416854-18426854:-1;chr21:45654111-45664111:1;chr21:45750759-45760759:-1;chr21:46881668-46891668:1;chr21:47036409-47046409:1;chr21:47058756-47068756:-1;chr21:47528556-47538556:1;chr21:47574070-47584070:-1;chr22:24590016-24600016:-1;chr22:25166534-25176534:1;chr22:32596234-32606234:-1;chr22:42625695-42635695:-1;chr22:50776853-50786853:-1;chrX:12861208-12871208:1;chrX:38138988-38148988:1;chrX:38285179-38295179:-1;chrX:61921173-61931173:1;chrX:123153889-123163889:1;chrX:123339100-123349100:-1;chrX:151840739-151850739:1;chrX:152930102-152940102:1;chrX:153049270-153059270:-1 hs1:9161452-9161579,hs1:204570469-204570615;hs1:53137309-53137473,hs17:64048067-64048196;hs1:199322203-199322330,hs1:199429411-199429534;hs1:204262717-204262931,hs1:205452828-205453072;hs2:55343228-55343371,hs2:55392497-55392633;hs2:232990373-232990583,hs2:232992829-232993022;hs3:49155131-49155298,hs3:49422496-49422710;hs3:183615303-183615476,hs3:183906521-183906687;hs3:183627058-183627267,hs3:183904839-183905040;hs3:183655936-183656074,hs3:183699572-183699719;hs3:183695899-183696100,hs3:183838326-183838487;hs3:183696737-183696855,hs3:183945419-183945547;hs3:183716770-183716990,hs3:183777766-183777996;hs3:183731927-183732050,hs3:183865488-183865612;hs3:183733872-183734052,hs3:183769393-183769542;hs3:183779412-183779546,hs3:183866442-183866596;hs3:183794779-183794980,hs3:183837559-183837721;hs3:183873979-183874100,hs3:183880959-183881082;hs5:141113539-141113751,hs5:141114494-141114711;hs7:35623407-35623556,hs7:35942836-35942995;hs7:52839471-52839653,hs7:55285530-55285690;hs7:53483332-53483478,hs7:53819672-53819811;hs7:53563991-53564155,hs7:53600133-53600308;hs7:54576047-54576165,hs7:54632154-54632280;hs7:54618097-54618281,hs7:54619930-54620119;hs7:139498898-139499039,hs7:139884851-139885031;hs9:17842948-17843096,hs9:35021021-35021175;hs9:17843928-17844074,hs9:35020492-35020632;hs9:17845353-17845518,hs9:17846499-17846669;hs9:17957299-17957476,hs9:18358028-18358205;hs9:18059067-18059186,hs9:34976509-34976704;hs9:18136594-18136743,hs9:18211577-18211797;hs9:18137948-18138178,hs9:34991930-34992108;hs9:18138144-18138259,hs9:34964798-34964927;hs9:18138549-18138724,hs9:34976736-34976930;hs9:18138585-18138696,hs9:36219149-36219270;hs9:18188308-18188456,hs9:34983577-34983737;hs9:21675676-21675854,hs9:21885078-21885237;hs9:22018752-22018886,hs9:22058399-22058563;hs9:22057663-22057796,hs9:22685383-22685554;hs9:22066997-22067177,hs9:22640069-22640256;hs10:5389009-5389127,hs10:69590565-69590713;hs10:25526061-25526208,hs10:26528940-26529154;hs10:25528020-25528183,hs10:26618476-26618675;hs10:26137042-26137236,hs10:26668657-26668813;hs10:26178323-26178482,hs10:27402415-27402617;hs10:26185777-26185974,hs10:28570226-28570425;hs10:26213706-26213864,hs10:26471874-26472030;hs10:26228994-26229211,hs10:28361984-28362172;hs10:26234071-26234257,hs10:27560151-27560301;hs10:26301663-26301836,hs10:26394266-26394461;hs10:26352717-26352839,hs10:27621185-27621318;hs10:26416342-26416518,hs10:27452277-27452452;hs10:26424478-26424598,hs10:27624650-27624797;hs10:26427858-26428051,hs10:27702026-27702232;hs10:26449719-26449908,hs10:27708513-27708709;hs10:26465225-26465449,hs10:26709600-26709809;hs10:26499096-26499235,hs10:26521017-26521169;hs10:26511026-26511206,hs9:36217084-36217275;hs10:26586863-26587058,hs10:28521985-28522208;hs10:26616873-26617031,hs10:28609730-28609901;hs10:26687182-26687388,hs10:26704259-26704448;hs10:27187396-27187584,hs10:28405432-28405568;hs10:27267829-27268007,hs10:27437160-27437354;hs10:27298876-27299013,hs10:27392411-27392581;hs10:27408124-27408287,hs10:27489165-27489340;hs10:27439517-27439692,hs10:27629862-27630018;hs10:27441179-27441352,hs10:28484957-28485136;hs10:27455797-27455935,hs9:34973777-34973892;hs10:27482129-27482298,hs10:28349959-28350118;hs10:27496695-27496896,hs10:27627865-27628016;hs10:27500688-27500846,hs10:39059094-39059296;hs10:27536869-27537046,hs10:27987884-27988046;hs10:27556424-27556652,hs10:64332508-64332703;hs10:27624276-27624420,hs10:39004814-39004961;hs10:28002611-28002805,hs10:28612088-28612303;hs10:28088077-28088253,hs10:64327091-64327251;hs10:28131311-28131508,hs10:28675386-28675571;hs10:28216131-28216324,hs10:28572960-28573137;hs10:28265499-28265666,hs10:64381456-64381653;hs10:28273457-28273656,hs10:39001717-39001884;hs10:28482593-28482734,hs10:64340641-64340816;hs10:28514291-28514470,hs10:64301596-64301789;hs10:38950382-38950603,hs2:92087389-92087493;hs10:38984662-38984791,hs10:64335864-64336010;hs10:39013743-39013886,hs10:64341826-64341991;hs10:69530566-69530709,hs10:81440084-81440249;hs10:89614912-89615041,hs10:90008109-90008247;hs10:90082404-90082550,hs10:90083136-90083290;hs11:22710346-22710513,hs9:36085441-36085604;hs11:22711488-22711625,hs9:36031746-36031945;hs11:85898806-85898988,hs11:85986876-85987009;hs12:27949327-27949470,hs2:215771542-215771683;hs14:20403609-20403811,hs14:40734808-40734972;hs14:21740037-21740143,hs8:95816288-95816395;hs14:39102655-39102875,hs14:40657702-40657908;hs14:39103683-39103859,hs14:40502442-40502642;hs14:39153952-39154097,hs14:40734345-40734485;hs15:29830554-29830672,hs15:35421233-35421427;hs15:97764805-97764979,hs15:97765518-97765707;hs17:34053379-34053607,hs17:34138123-34138262;hs17:41621666-41621811,hs2:43110619-43110794 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22903, USA Tumor genomes are generally thought to evolve through a gradual accumulation of mutations, but the observation that extraordinarily complex rearrangements can arise through single mutational events suggests that evolution may be accelerated by punctuated changes in genome architecture. To assess the prevalence and origins of complex genomic rearrangements (CGRs), we mapped 6179 somatic structural variation breakpoints in 64 cancer genomes from seven tumor types and screened for clusters of three or more interconnected breakpoints. We find that complex breakpoint clusters are extremely common: 154 clusters comprise 25% of all somatic breakpoints, and 75% of tumors exhibit at least one complex cluster. Based on copy number state profiling, 63% of breakpoint clusters are consistent with being CGRs that arose through a single mutational event. CGRs have diverse architectures including focal breakpoint clusters, large-scale rearrangements joining clusters from one or more chromosomes, and staggeringly complex chromothripsis events. Notably, chromothripsis has a significantly higher incidence in glioblastoma samples (39%) relative to other tumor types (9%). Chromothripsis breakpoints also show significantly elevated intra-tumor allele frequencies relative to simple SVs, which indicates that they arise early during tumorigenesis or confer selective advantage. Finally, assembly and analysis of 4002 somatic and 6982 germline breakpoint sequences reveal that somatic breakpoints show significantly less microhomology and fewer templated insertions than germline breakpoints, and this effect is stronger at CGRs than at simple variants. These results are inconsistent with replication-based models of CGR genesis and strongly argue that nonhomologous repair of concurrently arising DNA double-strand breaks is the predominant mechanism underlying complex cancer genome rearrangements. GRCh37/hg19 Yes NA CTDB0233 Research 23410887 Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA, Layer RM, Quinlan AR, Hall IM Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms Genome Research 2013 May 2,17 Non Small-cell lung cancer Next Generation Sequencing Homo sapiens LUAD_1_T Illumina paired-end sequencing chr1:148940228-148950228:-1;chr1:149936099-149946099:-1;chr1:152197617-152207617:1;chr1:152315064-152325064:-1;chr1:157316602-157326602:-1;chr1:197559930-197569930:1;chr1:207631620-207641620:1;chr1:207888651-207898651:-1;chr2:11400508-11410508:-1;chr2:11436066-11446066:1;chr2:38540683-38550683:1;chr2:39257158-39267158:-1;chr2:39282681-39292681:1;chr2:41531621-41541621:-1;chr2:41546798-41556798:1;chr2:86028254-86038254:-1;chr2:86078657-86088657:1;chr2:124605911-124615911:1;chr2:132978550-132988550:-1;chr3:193381476-193391476:-1;chr3:193396666-193406666:1;chr4:9813954-9823954:-1;chr4:179490192-179500192:-1;chr4:179510276-179520276:1;chr5:45905339-45915339:-1;chr5:56315967-56325967:-1;chr5:71945183-71955183:-1;chr5:72040614-72050614:1;chr5:99748808-99758808:1;chr5:122137209-122147209:-1;chr5:122167980-122177980:1;chr5:138855975-138865975:1;chr5:165180957-165190957:-1;chr5:165216420-165226420:1;chr5:180679560-180689560:1;chr6:57428986-57438986:-1;chr6:57480768-57490768:1;chr6:95624366-95634366:-1;chr6:95634641-95644641:1;chr7:32667085-32677085:1;chr7:32851742-32861742:1;chr7:106945234-106955234:-1;chr7:106992032-107002032:1;chr7:111616013-111626013:-1;chr8:111020753-111030753:-1;chr8:117778597-117788597:1;chr8:127048441-127058441:-1;chr10:2376201-2386201:-1;chr10:118762650-118772650:-1;chr10:118778064-118788064:1;chr10:128454292-128464292:-1;chr10:131768628-131778628:-1;chr11:85686911-85696911:-1;chr11:85697359-85707359:1;chr11:127200702-127210702:-1;chr12:34529334-34539334:-1;chr12:133804878-133814878:1;chr13:19481471-19491471:-1;chr13:21881835-21891835:-1;chr13:39607322-39617322:-1;chr13:51064467-51074467:1;chr14:70918701-70928701:1;chr14:71476489-71486489:1;chr15:85948730-85958730:-1;chr15:85964235-85974235:1;chr16:33901402-33911402:1;chr16:73673067-73683067:-1;chr16:73688402-73698402:1;chr17:21456957-21466957:1;chr19:24588662-24598662:-1;chr19:27727495-27737495:1;chr21:9822869-9832869:-1;chr22:28247796-28257796:-1;chrX:21287666-21297666:-1;chrX:21317929-21327929:1;chrX:41205597-41215597:1;chrY:21479752-21489752:-1 hs1:67662697-67662953,hs1:233747886-233748131;hs1:67703934-67704113,hs1:234390975-234391159;hs1:67780997-67781267,hs1:195983406-195983636;hs1:74792790-74792960,hs1:74796480-74796674;hs2:89302599-89302803,hs2:124335000-124335193;hs2:95329273-95329446,hs2:116874022-116874292;hs2:102517743-102517860,hs2:104620327-104620644;hs2:104629776-104629972,hs2:117429240-117429370;hs2:170655803-170655988,hs2:202125711-202125899;hs2:170786393-170786611,hs2:202131323-202131565;hs2:201341700-201341951,hs2:202135719-202136013;hs4:96044249-96044379,hs4:96046029-96046288;hs5:25187734-25187930,hs8:69393370-69393573;hs6:6742975-6743057,hs6:6746597-6746832;hs9:33356561-33356785,hs9:35409720-35409960;hs13:57758221-57758409,hs13:57789127-57789282;hs17:4960469-4960766,hs2:86085633-86085807;hs17:5173123-5173207,hs17:15192589-15192726;hs17:5234872-5235096,hs17:15224741-15224995;hs17:13380866-13381164,hs2:104610499-104610757;hs17:14148681-14148853,hs2:124328944-124329102;hs17:14355131-14355364,hs17:21248423-21248665;hs17:14676724-14676991,hs2:88931961-88932190;hs17:15272955-15273201,hs17:16587537-16587824;hs17:15274207-15274472,hs2:124330365-124330612;hs17:15372418-15372664,hs2:88930900-88931136;hs17:15737992-15738207,hs17:21251465-21251671;hs17:15867193-15867484,hs17:22127631-22127868;hs17:21251312-21251541,hs2:124331647-124331904;hs17:21402352-21402596,hs2:86034683-86034949;hs18:2666733-2666912,hs18:3029184-3029362;hs19:43038834-43039060,hs19:43809952-43810148 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22903, USA Tumor genomes are generally thought to evolve through a gradual accumulation of mutations, but the observation that extraordinarily complex rearrangements can arise through single mutational events suggests that evolution may be accelerated by punctuated changes in genome architecture. To assess the prevalence and origins of complex genomic rearrangements (CGRs), we mapped 6179 somatic structural variation breakpoints in 64 cancer genomes from seven tumor types and screened for clusters of three or more interconnected breakpoints. We find that complex breakpoint clusters are extremely common: 154 clusters comprise 25% of all somatic breakpoints, and 75% of tumors exhibit at least one complex cluster. Based on copy number state profiling, 63% of breakpoint clusters are consistent with being CGRs that arose through a single mutational event. CGRs have diverse architectures including focal breakpoint clusters, large-scale rearrangements joining clusters from one or more chromosomes, and staggeringly complex chromothripsis events. Notably, chromothripsis has a significantly higher incidence in glioblastoma samples (39%) relative to other tumor types (9%). Chromothripsis breakpoints also show significantly elevated intra-tumor allele frequencies relative to simple SVs, which indicates that they arise early during tumorigenesis or confer selective advantage. Finally, assembly and analysis of 4002 somatic and 6982 germline breakpoint sequences reveal that somatic breakpoints show significantly less microhomology and fewer templated insertions than germline breakpoints, and this effect is stronger at CGRs than at simple variants. These results are inconsistent with replication-based models of CGR genesis and strongly argue that nonhomologous repair of concurrently arising DNA double-strand breaks is the predominant mechanism underlying complex cancer genome rearrangements. GRCh37/hg19 Yes NA CTDB0234 Research 23410887 Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA, Layer RM, Quinlan AR, Hall IM Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms Genome Research 2013 May 8,20 Non Small-cell lung cancer Next Generation Sequencing Homo sapiens LUAD_5_T Illumina paired-end sequencing chr1:1473900-1483900:-1;chr1:19791629-19801629:1;chr1:25872018-25882018:-1;chr1:25897191-25907191:1;chr1:30163240-30173240:-1;chr1:31507748-31517748:1;chr1:31647272-31657272:-1;chr1:39301689-39311689:1;chr1:49057351-49067351:-1;chr1:49212517-49222517:1;chr1:151656611-151666611:-1;chr1:153538084-153548084:1;chr1:154572808-154582808:1;chr1:155064621-155074621:1;chr1:156328554-156338554:-1;chr1:160847890-160857890:1;chr1:161003814-161013814:-1;chr1:161105474-161115474:1;chr1:161121368-161131368:-1;chr1:161196834-161206834:1;chr1:204028110-204038110:-1;chr1:207969704-207979704:-1;chr1:239026885-239036885:1;chr1:239042215-239052215:-1;chr2:32574660-32584660:-1;chr2:32660325-32670325:1;chr2:43270801-43280801:-1;chr2:43307437-43317437:1;chr2:44104207-44114207:1;chr2:61880475-61890475:-1;chr2:135181074-135191074:-1;chr2:135372168-135382168:1;chr2:142393555-142403555:-1;chr2:142428616-142438616:1;chr2:142634772-142644772:-1;chr2:182759677-182769677:-1;chr2:183985385-183995385:1;chr2:203050636-203060636:1;chr2:204291835-204301835:-1;chr2:204362381-204372381:1;chr2:204419012-204429012:-1;chr2:218453718-218463718:-1;chr2:218893645-218903645:1;chr2:228494896-228504896:1;chr3:4537572-4547572:-1;chr3:20039846-20049846:1;chr3:20070261-20080261:-1;chr3:40469038-40479038:1;chr3:40605222-40615222:-1;chr3:84409039-84419039:-1;chr3:85930316-85940316:1;chr3:86478603-86488603:-1;chr3:88757284-88767284:1;chr3:89956514-89966514:-1;chr3:93837368-93847368:1;chr3:101137084-101147084:1;chr3:101545413-101555413:-1;chr3:108971520-108981520:1;chr3:109141933-109151933:-1;chr3:109162001-109172001:1;chr3:111135352-111145352:-1;chr3:111367173-111377173:1;chr3:111717450-111727450:-1;chr3:113608707-113618707:-1;chr3:118005527-118015527:1;chr3:144982838-144992838:-1;chr3:146530263-146540263:1;chr3:147569361-147579361:-1;chr3:151198476-151208476:1;chr3:161665031-161675031:1;chr3:164543904-164553904:-1;chr3:164980417-164990417:1;chr3:166787296-166797296:-1;chr3:177036375-177046375:-1;chr3:181488159-181498159:1;chr4:82914875-82924875:-1;chr4:82981141-82991141:1;chr4:100301293-100311293:-1;chr4:100380410-100390410:1;chr5:2735260-2745260:1;chr5:133844066-133854066:1;chr5:134215045-134225045:-1;chr5:138855975-138865975:1;chr6:2436103-2446103:1;chr6:52180968-52190968:-1;chr6:52251583-52261583:1;chr6:52774905-52784905:1;chr6:57603233-57613233:1;chr6:63351018-63361018:-1;chr7:6077351-6087351:1;chr7:6149404-6159404:-1;chr7:6316906-6326906:1;chr7:13122681-13132681:-1;chr7:30098006-30108006:-1;chr7:62507528-62517528:1;chr7:119483586-119493586:-1;chr7:153394377-153404377:1;chr8:3989600-3999600:1;chr8:3999600-4009600:-1;chr8:90921832-90931832:-1;chr8:91395950-91405950:1;chr8:99133205-99143205:-1;chr8:111185949-111195949:1;chr8:114385185-114395185:-1;chr8:141518033-141528033:-1;chr8:144104701-144114701:1;chr10:5016719-5026719:-1;chr10:5140638-5150638:1;chr10:5258590-5268590:1;chr10:5348322-5358322:-1;chr10:5368698-5378698:1;chr10:5813822-5823822:1;chr10:5829274-5839274:1;chr10:25007461-25017461:1;chr10:57398452-57408452:-1;chr10:70105680-70115680:1;chr10:88134773-88144773:1;chr10:88387439-88397439:-1;chr10:105051776-105061776:1;chr10:105170418-105180418:-1;chr10:122787196-122797196:-1;chr10:131768628-131778628:-1;chr11:9508575-9518575:-1;chr11:19507265-19517265:-1;chr11:20644954-20654954:-1;chr11:20714623-20724623:1;chr11:33225611-33235611:1;chr11:33560842-33570842:-1;chr11:38037131-38047131:1;chr11:38052359-38062359:-1;chr11:38393231-38403231:1;chr11:129946170-129956170:-1;chr12:24227585-24237585:-1;chr12:24247742-24257742:1;chr12:38085549-38095549:-1;chr12:53143127-53153127:-1;chr12:53270470-53280470:1;chr12:53437353-53447353:-1;chr12:53467575-53477575:1;chr12:53519417-53529417:1;chr12:54691312-54701312:1;chr12:54717244-54727244:-1;chr12:99083060-99093060:-1;chr12:99557731-99567731:1;chr12:114618459-114628459:1;chr12:123309461-123319461:-1;chr12:123380764-123390764:1;chr12:123416856-123426856:-1;chr12:124206909-124216909:-1;chr13:24446391-24456391:1;chr13:30419412-30429412:-1;chr13:30459419-30469419:1;chr13:70841059-70851059:-1;chr14:32325246-32335246:-1;chr14:32642619-32652619:1;chr14:33784750-33794750:1;chr14:37682923-37692923:1;chr14:49010771-49020771:-1;chr14:50576851-50586851:1;chr14:71262375-71272375:-1;chr14:71413273-71423273:-1;chr14:72063436-72073436:1;chr14:72146974-72156974:-1;chr14:72217218-72227218:1;chr14:72340204-72350204:-1;chr14:72856753-72866753:1;chr14:73667509-73677509:-1;chr14:73753224-73763224:1;chr14:73973547-73983547:-1;chr14:74180200-74190200:-1;chr14:74266161-74276161:1;chr14:74654924-74664924:-1;chr14:74761248-74771248:1;chr14:74854909-74864909:-1;chr14:74894938-74904938:1;chr14:74920383-74930383:-1;chr14:75136819-75146819:1;chr14:75172252-75182252:1;chr14:75242260-75252260:-1;chr14:84646896-84656896:1;chr14:92109332-92119332:1;chr15:55699591-55709591:1;chr15:74891751-74901751:-1;chr15:79039119-79049119:1;chr16:9039960-9049960:1;chr16:72548662-72558662:1;chr16:76878298-76888298:-1;chr16:79135166-79145166:-1;chr16:79230334-79240334:1;chr17:19915703-19925703:-1;chr17:49417579-49427579:-1;chr17:50144761-50154761:1;chr17:71325932-71335932:-1;chr17:71794748-71804748:1;chr18:40115675-40125675:1;chr18:40133942-40143942:-1;chr19:14119636-14129636:1;chr19:39211411-39221411:1;chr19:39949974-39959974:-1;chr19:39959990-39969990:1;chr19:46893075-46903075:1;chr20:3814075-3824075:1;chr20:3835311-3845311:-1;chr20:5905830-5915830:-1;chr20:30304572-30314572:1;chr20:30366000-30376000:-1;chr20:30820991-30830991:1;chr20:31008482-31018482:-1;chr20:31873696-31883696:1;chr20:37524413-37534413:-1;chr20:42203048-42213048:1;chr20:46249131-46259131:-1;chr20:47458689-47468689:1;chr20:50251402-50261402:1;chr20:50818836-50828836:-1;chr20:52076833-52086833:1;chr20:52426549-52436549:-1;chr20:55259700-55269700:-1;chr20:62123128-62133128:1;chr20:62722363-62732363:-1;chr21:18788104-18798104:1;chr21:18959750-18969750:-1;chr21:20853894-20863894:-1;chr21:22005278-22015278:-1;chr21:22261760-22271760:1;chr21:22676091-22686091:1;chr21:24429157-24439157:1;chr21:24444411-24454411:-1;chr21:27098175-27108175:-1;chr21:27917473-27927473:1;chr22:18253405-18263405:-1;chr22:18452999-18462999:1;chr22:18904904-18914904:-1;chr22:27223549-27233549:-1;chr22:27933459-27943459:1;chr22:28338718-28348718:-1;chr22:28374004-28384004:-1;chr22:28914596-28924596:1;chr22:31033099-31043099:-1;chr22:31734312-31744312:1;chr22:36671683-36681683:-1;chr22:36759060-36769060:1;chr22:36878159-36888159:-1;chr22:37231099-37241099:-1;chr22:39960402-39970402:1;chr22:40884155-40894155:1;chrX:24037502-24047502:1;chrX:34069606-34079606:-1 hs1:16382204-16382460,hs1:16389848-16390009;hs1:35156476-35156639,hs1:35158268-35158455;hs1:51785546-51785741,hs1:51800352-51800558;hs1:78087551-78087751,hs1:78088884-78089144;hs1:85241490-85241705,hs1:85273463-85273710;hs1:108379284-108379465,hs1:108380946-108381141;hs1:108380981-108381192,hs1:108384799-108385106;hs1:113996259-113996455,hs1:114013113-114013271;hs1:159478901-159479179,hs1:159482347-159482583;hs1:185687470-185687713,hs1:185689347-185689537;hs1:204229301-204229428,hs1:204268601-204268857;hs1:224777366-224777628,hs1:224800926-224801181;hs1:224777687-224777805,hs1:224801295-224801421;hs1:224781329-224781534,hs1:224783524-224783745;hs2:4567276-4567439,hs3:123592292-123592458;hs2:14570509-14570664,hs4:175737521-175737668;hs2:17657352-17657454,hs2:17847555-17847740;hs2:35019256-35019486,hs2:35054553-35054882;hs2:36293692-36293833,hs2:36335849-36335980;hs2:104625918-104626109,hs2:104627776-104627936;hs2:123580220-123580431,hs2:123599344-123599579;hs2:135186937-135187231,hs2:135380775-135381056;hs2:140922929-140923178,hs2:141321010-141321282;hs2:140937232-140937496,hs2:141032435-141032706;hs2:140955643-140955876,hs2:141143365-141143670;hs2:141704376-141704566,hs2:141732157-141732442;hs2:141781762-141781968,hs2:142139362-142139588;hs2:142389265-142389487,hs2:142549503-142549695;hs2:142445553-142445748,hs2:142674894-142675149;hs2:144906208-144906467,hs2:221532698-221532974;hs2:146066431-146066596,hs2:146068880-146069139;hs2:165211288-165211448,hs2:165316222-165316402;hs2:166874561-166874755,hs2:166877729-166877882;hs2:181771567-181771827,hs2:181779814-181780094;hs2:182764983-182765223,hs2:183989658-183989918;hs2:225530080-225530377,hs2:225557819-225558063;hs2:228611725-228611878,hs2:228616759-228616972;hs3:4541543-4541708,hs3:5240371-5240572;hs3:52783742-52783963,hs3:52812351-52812630;hs3:69118990-69119225,hs6:107980186-107980378;hs3:83021587-83021873,hs3:83059006-83059225;hs3:84403901-84404166,hs3:86481935-86482201;hs3:84990369-84990652,hs3:84991680-84991957;hs3:85935697-85935967,hs3:111141090-111141375;hs3:89962639-89962898,hs3:146536796-146537145;hs3:93844011-93844298,hs3:109171071-109171182;hs3:96456884-96457076,hs3:164551259-164551539;hs3:101142436-101142663,hs3:101549672-101549879;hs3:106858227-106858485,hs3:106877263-106877517;hs3:111721859-111722129,hs3:161668569-161668869;hs3:117534313-117534490,hs3:117536083-117536225;hs3:151205089-151205341,hs3:157002866-157003139;hs3:162943803-162944039,hs3:164988530-164988845;hs3:163587559-163587742,hs3:163638409-163638627;hs3:183823089-183823356,hs3:183840863-183841144;hs3:189061865-189062068,hs3:189210930-189211145;hs3:192630763-192631051,hs3:193638537-193638752;hs4:21983869-21984152,hs4:21987572-21987838;hs4:69678728-69678850,hs4:69889105-69889379;hs4:100305167-100305350,hs4:100387374-100387561;hs5:3664861-3664994,hs5:3666777-3666901;hs5:57087920-57088047,hs5:57097618-57097795;hs5:58876156-58876509,hs5:59104313-59104596;hs5:82560984-82561181,hs5:82643361-82643545;hs5:112707093-112707329,hsX:120298367-120298660;hs5:170659885-170660119,hs5:170708476-170708756;hs5:180260889-180261153,hs5:180262738-180262877;hs6:47548468-47548723,hs6:47550394-47550608;hs6:52184833-52184977,hs6:80172199-80172365;hs6:52777236-52777529,hs6:63378706-63378996;hs6:63355668-63355943,hs6:63380088-63380386;hs6:74344978-74345133,hs6:74346141-74346243;hs6:75134256-75134420,hs6:75193072-75193206;hs6:112287612-112287761,hs6:112296388-112296562;hs6:150690568-150690721,hs6:155360112-155360306;hs6:154314325-154314566,hs6:155386791-155387104;hs6:154314594-154314822,hs6:155451396-155451602;hs6:162972924-162973184,hs6:162975575-162975826;hs7:4309106-4309265,hs7:4337548-4337766;hs7:50229072-50229237,hs7:50232881-50233045;hs7:89112738-89112904,hs7:89125947-89126075;hs7:90667582-90667783,hs7:90685063-90685284;hs7:92469938-92470205,hs7:92472816-92473071;hs8:25602217-25602435,hs8:25617848-25618076;hs8:56923612-56923805,hs8:107513783-107513972;hs8:59384511-59384785,hs8:59388294-59388532;hs8:71818464-71818675,hs8:71846372-71846619;hs8:75254982-75255121,hs8:75256241-75256386;hs8:79550212-79550399,hs8:82220340-82220536;hs8:82030224-82030481,hs8:99074705-99074909;hs8:84119064-84119279,hs8:111194191-111194406;hs8:85367585-85367807,hs8:85404778-85404989;hs8:88582474-88582629,hs8:99074458-99074622;hs8:90933173-90933306,hs8:91401864-91401984;hs8:99079686-99079928,hs8:143935120-143935369;hs8:114645051-114645291,hs8:114654041-114654286;hs8:121810705-121810830,hs8:121812627-121812739;hs9:10031779-10031971,hs9:10089545-10089676;hs9:129888457-129888626,hs9:130527153-130527300;hs9:135473448-135473755,hs9:135481108-135481324;hs10:5023804-5024087,hs10:5164584-5164857;hs10:5024969-5025077,hs10:5267612-5267744;hs10:5353223-5353335,hs10:5373768-5373931;hs10:5372636-5372815,hs16:57186767-57186967;hs10:12547165-12547396,hs10:12552780-12553034;hs10:36245756-36245875,hs10:37687495-37687713;hs10:75186028-75186270,hs10:75189870-75190166;hs10:98997154-98997360,hs10:99038258-99038498;hs10:104487525-104487760,hs10:104496669-104496926;hs10:108870417-108870582,hs10:109065887-109066084;hs10:115686438-115686723,hs10:115737740-115738017;hs11:18224651-18224829,hs11:18331894-18332070;hs11:20648089-20648378,hs11:20730716-20730983;hs11:20833450-20833625,hs3:190305212-190305364;hs11:25701636-25701877,hs22:29065356-29065551;hs11:38400262-38400562,hs14:92116742-92117035;hs11:60807874-60808131,hs11:60811875-60812119;hs11:85355831-85356056,hs11:85370350-85370623;hs11:111918615-111918862,hs11:111956541-111956823;hs11:122711536-122711694,hs11:129881437-129881579;hs12:3607902-3608052,hs13:75706172-75706381;hs12:3607924-3608152,hs17:49885672-49885904;hs12:3608210-3608339,hs14:32625942-32626198;hs12:46028805-46029069,hs12:46061787-46062063;hs12:98048193-98048365,hs12:99561322-99561508;hs12:99034150-99034341,hs12:99665152-99665411;hs12:120751649-120751856,hs12:120756302-120756583;hs13:21598736-21598951,hs14:71157146-71157394;hs13:21598864-21599057,hs6:99717945-99718139;hs13:33284723-33284972,hs9:131325424-131325719;hs13:37389307-37389551,hs6:90846728-90846979;hs13:37389853-37390136,hs6:90846399-90846672;hs13:76348980-76349215,hs2:103918577-103918791;hs13:76534267-76534581,hs13:76543336-76543600;hs13:79826549-79826813,hs13:79830013-79830326;hs13:80969719-80969916,hs13:80970894-80971163;hs13:83189418-83189710,hs8:119201786-119202036;hs13:88197434-88197594,hs13:88200190-88200361;hs13:100161322-100161587,hs13:100177238-100177462;hs13:105247009-105247260,hs13:105255859-105256061;hs14:32930138-32930305,hs14:84503122-84503293;hs14:33787246-33787421,hs14:49017453-49017619;hs14:43509921-43510207,hs14:44214614-44214872;hs14:44421991-44422184,hs14:84901220-84901397;hs14:56501001-56501167,hs14:97406836-97407099;hs14:60921365-60921583,hs14:60930461-60930653;hs14:68650913-68651076,hs14:68654268-68654489;hs14:72060807-72061077,hs14:72063002-72063314;hs14:74354423-74354622,hs14:74362599-74362784;hs14:100530759-100530884,hs2:232162661-232162824;hs15:37510087-37510341,hs15:37521779-37522036;hs15:50508416-50508577,hs15:50516141-50516295;hs15:77261563-77261821,hs15:77265712-77265984;hs15:90668155-90668477,hs15:90725886-90726200;hs16:63497526-63497796,hs16:63540839-63541107;hs16:72551937-72552155,hs16:73027339-73027515;hs16:73188058-73188195,hs16:73189251-73189420;hs16:79139050-79139279,hs16:79222456-79222676;hs17:1284312-1284526,hs17:1287544-1287746;hs17:14288010-14288280,hs3:123594768-123595012;hs17:18879667-18879868,hs17:18886701-18886903;hs17:38071674-38071981,hs17:38097304-38097585;hs17:44803251-44803459,hs17:44804984-44805271;hs17:59779887-59780089,hs17:60068755-60068942;hs17:70213343-70213523,hs17:79699593-79699742;hs17:78951608-78951901,hs17:78957909-78958126;hs18:3584065-3584250,hs18:3587966-3588202;hs18:9304604-9304923,hs18:9306763-9306985;hs18:71258644-71258885,hs18:71378562-71378813;hs19:11679319-11679484,hs19:11681898-11682075;hs19:33537515-33537748,hs19:33585360-33585611;hs20:8617966-8618200,hs8:82370743-82371016;hs20:8626523-8626793,hs8:82030477-82030878;hs20:20691672-20691871,hs8:99062995-99063171;hs20:20950844-20951039,hs8:99046790-99047003;hs20:23413231-23413456,hs8:78684134-78684294;hs20:31863582-31863838,hs8:82146539-82146802;hs20:37792426-37792691,hs8:79619075-79619351;hs20:61623054-61623178,hs20:61654174-61654308;hs21:10970448-10970777,hs21:20661153-20661463;hs21:23948932-23949053,hs4:150377132-150377256;hs21:24430987-24431276,hs21:24449842-24450092;hs21:25927551-25927727,hs21:26969712-26969947;hs21:30563688-30563885,hs21:31306096-31306282;hs21:37186860-37187085,hs21:37190336-37190509;hs21:38559973-38560286,hs21:38827838-38828119;hs21:42056175-42056455,hs21:42058651-42058908;hsX:109171077-109171322,hsX:109217183-109217343;hsX:119555397-119555649,hsX:120450873-120451163 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22903, USA Tumor genomes are generally thought to evolve through a gradual accumulation of mutations, but the observation that extraordinarily complex rearrangements can arise through single mutational events suggests that evolution may be accelerated by punctuated changes in genome architecture. To assess the prevalence and origins of complex genomic rearrangements (CGRs), we mapped 6179 somatic structural variation breakpoints in 64 cancer genomes from seven tumor types and screened for clusters of three or more interconnected breakpoints. We find that complex breakpoint clusters are extremely common: 154 clusters comprise 25% of all somatic breakpoints, and 75% of tumors exhibit at least one complex cluster. Based on copy number state profiling, 63% of breakpoint clusters are consistent with being CGRs that arose through a single mutational event. CGRs have diverse architectures including focal breakpoint clusters, large-scale rearrangements joining clusters from one or more chromosomes, and staggeringly complex chromothripsis events. Notably, chromothripsis has a significantly higher incidence in glioblastoma samples (39%) relative to other tumor types (9%). Chromothripsis breakpoints also show significantly elevated intra-tumor allele frequencies relative to simple SVs, which indicates that they arise early during tumorigenesis or confer selective advantage. Finally, assembly and analysis of 4002 somatic and 6982 germline breakpoint sequences reveal that somatic breakpoints show significantly less microhomology and fewer templated insertions than germline breakpoints, and this effect is stronger at CGRs than at simple variants. These results are inconsistent with replication-based models of CGR genesis and strongly argue that nonhomologous repair of concurrently arising DNA double-strand breaks is the predominant mechanism underlying complex cancer genome rearrangements. GRCh37/hg19 Yes NA CTDB0235 Research 23410887 Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA, Layer RM, Quinlan AR, Hall IM Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms Genome Research 2013 May 3,7 Non Small-cell lung cancer Next Generation Sequencing Homo sapiens LUSC_1_T Illumina paired-end sequencing chr1:110174616-110184616:1;chr1:117863955-117873955:-1;chr2:17237674-17247674:-1;chr2:39166903-39176903:-1;chr2:39343310-39353310:-1;chr2:68617207-68627207:1;chr2:74584625-74594625:-1;chr2:74604643-74614643:1;chr2:98886029-98896029:-1;chr2:100380369-100390369:1;chr2:172436011-172446011:-1;chr2:197830578-197840578:-1;chr2:197865973-197875973:1;chr2:206125567-206135567:-1;chr2:206175797-206185797:1;chr2:224188225-224198225:1;chr2:234631310-234641310:1;chr2:234654919-234664919:-1;chr3:54868490-54878490:-1;chr3:54913612-54923612:1;chr3:108076138-108086138:1;chr3:108091589-108101589:-1;chr3:111523330-111533330:-1;chr3:111667356-111677356:-1;chr3:112361611-112371611:1;chr3:115457198-115467198:1;chr3:121070932-121080932:-1;chr3:162438355-162448355:-1;chr3:183112735-183122735:1;chr3:183877649-183887649:-1;chr3:183907649-183917649:1;chr3:184410779-184420779:1;chr3:185581099-185591099:-1;chr3:185736433-185746433:1;chr3:193866021-193876021:-1;chr4:1993628-2003628:1;chr4:3951871-3961871:1;chr4:4105312-4115312:1;chr4:7299995-7309995:1;chr4:8856057-8866057:1;chr4:8871057-8881057:-1;chr4:12917739-12927739:1;chr4:39769663-39779663:-1;chr4:41313229-41323229:-1;chr4:41356370-41366370:-1;chr4:44004315-44014315:1;chr4:65181343-65191343:1;chr4:68128286-68138286:1;chr4:68146332-68156332:-1;chr5:49441885-49451885:-1;chr5:49642670-49652670:1;chr6:150256643-150266643:1;chr7:5822212-5832212:1;chr7:10777273-10787273:1;chr7:23155201-23165201:-1;chr7:23327435-23337435:1;chr7:50631902-50641902:1;chr7:128687355-128697355:-1;chr7:128717705-128727705:1;chr7:130404067-130414067:1;chr7:133229330-133239330:1;chr7:136626865-136636865:-1;chr7:137858406-137868406:-1;chr7:138876200-138886200:-1;chr7:138951156-138961156:1;chr7:140488357-140498357:-1;chr7:140768011-140778011:1;chr7:140952178-140962178:1;chr7:141033409-141043409:1;chr7:141565579-141575579:1;chr7:142445922-142455922:-1;chr7:142528023-142538023:1;chr7:143735665-143745665:-1;chr7:145311665-145321665:1;chr7:146728647-146738647:-1;chr7:146753896-146763896:1;chr7:146805095-146815095:-1;chr7:146901529-146911529:1;chr7:148277469-148287469:-1;chr7:148501062-148511062:1;chr7:149334899-149344899:-1;chr7:149542855-149552855:1;chr7:151166849-151176849:-1;chr7:151713609-151723609:1;chr7:152731740-152741740:1;chr8:34077130-34087130:-1;chr8:39725295-39735295:1;chr8:82429449-82439449:1;chr9:5516936-5526936:-1;chr9:5582768-5592768:1;chr9:44783996-44793996:-1;chr9:92987579-92997579:-1;chr9:141006140-141016140:1;chr10:81298027-81308027:-1;chr10:89467332-89477332:1;chr10:89728185-89738185:-1;chr10:105530013-105540013:-1;chr10:105620597-105630597:1;chr11:47243802-47253802:-1;chr11:47294425-47304425:-1;chr11:47849500-47859500:1;chr11:55473419-55483419:1;chr11:67742772-67752772:-1;chr13:25590516-25600516:-1;chr14:28414071-28424071:-1;chr15:22520531-22530531:1;chr15:45352830-45362830:-1;chr15:51853581-51863581:1;chr15:54094990-54104990:-1;chr16:24465970-24475970:-1;chr16:54413308-54423308:-1;chr16:85428893-85438893:1;chr16:85443732-85453732:-1;chr18:77861588-77871588:1;chr20:29937815-29947815:1;chr20:41927158-41937158:1;chr20:43211644-43221644:1;chr21:9822869-9832869:-1;chr22:19165006-19175006:-1;chr22:19251387-19261387:1;chr22:25454112-25464112:-1;chr22:39950402-39960402:-1;chr22:39960402-39970402:1;chr22:41112932-41122932:1;chrX:3121022-3131022:1;chrX:13087172-13097172:1 hs1:191412530-191412670,hs1:191414542-191414677;hs2:36403481-36403741,hs8:82432277-82432523;hs2:50183943-50184168,hs2:50185273-50185538;hs2:127879049-127879263,hs2:127880346-127880545;hs2:141065925-141066135,hs3:186373289-186373501;hs2:141066193-141066354,hs3:186373715-186373885;hs2:144639396-144639638,hs2:144647251-144647487;hs2:197835225-197835416,hs2:197870125-197870380;hs2:206131333-206131523,hs2:206179197-206179430;hs3:54870581-54870819,hs3:54918046-54918288;hs3:97003408-97003624,hs3:97005297-97005560;hs3:111674048-111674278,hs3:112366472-112366731;hs3:126081434-126081584,hs3:126082892-126083030;hs3:146177264-146177523,hs7:148285901-148286134;hs3:146199506-146199770,hs7:148281976-148282227;hs3:159322016-159322226,hs3:171513494-171513694;hs3:160359611-160359834,hs3:160360586-160360810;hs3:161855203-161855337,hs3:171513970-171514121;hs3:161944959-161945169,hs3:165907170-165907428;hs3:172783316-172783480,hs3:174420114-174420246;hs3:177119294-177119404,hs3:177135472-177135598;hs3:184276793-184276971,hs3:184403003-184403184;hs3:185586166-185586314,hs3:185744438-185744583;hs4:12923079-12923302,hs5:39795701-39795890;hs4:41310328-41310561,hs4:41342292-41342536;hs4:63742053-63742208,hs9:115559750-115559951;hs4:113403770-113403963,hs4:113499662-113499832;hs4:168462793-168462995,hs4:168476004-168476237;hs5:109479055-109479216,hs7:141025880-141026033;hs7:8060909-8061039,hsX:100267523-100267687;hs7:23159549-23159712,hs7:23330045-23330236;hs7:54136774-54136937,hs7:118968050-118968211;hs7:128700389-128700656,hs7:128701576-128701823;hs7:130412144-130412289,hs7:137856740-137856900;hs7:133237439-133237700,hs7:142442083-142442325;hs7:136630244-136630462,hs7:140775318-140775553;hs7:140492663-140492900,hs7:143740391-143740631;hs7:140492747-140492949,hs7:143740403-143740652;hs7:141030092-141030315,hs7:141572726-141572903;hs7:142530915-142531156,hs7:145315601-145315864;hs7:146731840-146732006,hs7:149985474-149985595;hs7:146759340-146759492,hs7:149547305-149547464;hs7:146809224-146809420,hs7:152635776-152635932;hs7:146903406-146903550,hs7:149800648-149800816;hs7:148283441-148283617,hs7:149969193-149969406;hs7:148285689-148285814,hs7:149969607-149969786;hs7:149340242-149340434,hs7:149442191-149442323;hs7:151173861-151174082,hs7:152631575-152631820;hs7:151716734-151716946,hs7:152725830-152725993;hs7:152721560-152721732,hs7:152737110-152737250;hs9:5524755-5524964,hs9:5589040-5589228;hs10:49926242-49926464,hs12:52908394-52908632;hs10:89472935-89473189,hs10:89735926-89736200;hs10:105532756-105532959,hs10:105626130-105626311;hs10:133531068-133531237,hs3:186374965-186375127;hs11:47301317-47301534,hs11:47854330-47854587;hs12:67361606-67361818,hs12:67363097-67363246;hs12:100800092-100800325,hs3:186374067-186374254;hs12:100800316-100800555,hs3:186373784-186374031;hs14:28273437-28273685,hs14:28422743-28422992;hs14:87299646-87299876,hs4:137213989-137214209;hs14:87299935-87300135,hs4:137213861-137214024;hs19:43467954-43468141,hs3:186378696-186378880;hs20:41933787-41934030,hs20:41958478-41958709;hs20:52256378-52256591,hs20:52257132-52257345;hs22:29065644-29065856,hs4:121140174-121140382;hsX:35881159-35881413,hsX:35883863-35884107 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22903, USA Tumor genomes are generally thought to evolve through a gradual accumulation of mutations, but the observation that extraordinarily complex rearrangements can arise through single mutational events suggests that evolution may be accelerated by punctuated changes in genome architecture. To assess the prevalence and origins of complex genomic rearrangements (CGRs), we mapped 6179 somatic structural variation breakpoints in 64 cancer genomes from seven tumor types and screened for clusters of three or more interconnected breakpoints. We find that complex breakpoint clusters are extremely common: 154 clusters comprise 25% of all somatic breakpoints, and 75% of tumors exhibit at least one complex cluster. Based on copy number state profiling, 63% of breakpoint clusters are consistent with being CGRs that arose through a single mutational event. CGRs have diverse architectures including focal breakpoint clusters, large-scale rearrangements joining clusters from one or more chromosomes, and staggeringly complex chromothripsis events. Notably, chromothripsis has a significantly higher incidence in glioblastoma samples (39%) relative to other tumor types (9%). Chromothripsis breakpoints also show significantly elevated intra-tumor allele frequencies relative to simple SVs, which indicates that they arise early during tumorigenesis or confer selective advantage. Finally, assembly and analysis of 4002 somatic and 6982 germline breakpoint sequences reveal that somatic breakpoints show significantly less microhomology and fewer templated insertions than germline breakpoints, and this effect is stronger at CGRs than at simple variants. These results are inconsistent with replication-based models of CGR genesis and strongly argue that nonhomologous repair of concurrently arising DNA double-strand breaks is the predominant mechanism underlying complex cancer genome rearrangements. GRCh37/hg19 Yes NA CTDB0236 Research 23410887 Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA, Layer RM, Quinlan AR, Hall IM Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms Genome Research 2013 May 4 Non Small-cell lung cancer Next Generation Sequencing Homo sapiens LUSC_6_T Illumina paired-end sequencing chr1:2621456-2631456:1;chr1:12875195-12885195:1;chr2:53487784-53497784:-1;chr2:61757332-61767332:1;chr2:69621469-69631469:1;chr3:16681981-16691981:1;chr3:16692016-16702016:-1;chr3:123954097-123964097:-1;chr3:123994333-124004333:1;chr3:125894402-125904402:-1;chr3:126137175-126147175:-1;chr3:126238053-126248053:1;chr3:126826061-126836061:-1;chr3:127201582-127211582:1;chr3:160193597-160203597:-1;chr3:161781275-161791275:1;chr3:162070154-162080154:1;chr3:162213236-162223236:-1;chr3:162223432-162233432:-1;chr3:163651024-163661024:1;chr3:164710418-164720418:1;chr3:164805791-164815791:-1;chr3:166261326-166271326:-1;chr3:169184907-169194907:1;chr3:171676517-171686517:1;chr3:171758212-171768212:-1;chr3:172102009-172112009:-1;chr3:172418761-172428761:1;chr3:173302406-173312406:-1;chr3:174210577-174220577:1;chr3:174455890-174465890:1;chr3:174561287-174571287:-1;chr3:174643697-174653697:-1;chr3:174764522-174774522:1;chr3:177036375-177046375:-1;chr3:177736190-177746190:-1;chr3:177771312-177781312:1;chr3:178732630-178742630:1;chr3:181662670-181672670:-1;chr3:182006156-182016156:-1;chr3:182149281-182159281:-1;chr3:182810497-182820497:1;chr3:182877795-182887795:1;chr3:182954983-182964983:-1;chr3:184518058-184528058:-1;chr3:184864947-184874947:1;chr3:189358868-189368868:1;chr3:189368884-189378884:-1;chr4:65151104-65161104:1;chr4:65166112-65176112:-1;chr4:84488129-84498129:1;chr4:116644241-116654241:1;chr4:116837164-116847164:-1;chr4:156873692-156883692:1;chr4:185728917-185738917:1;chr5:7269171-7279171:1;chr5:19868916-19878916:1;chr5:49400855-49410855:1;chr6:57353526-57363526:-1;chr6:151154680-151164680:1;chr6:151191757-151201757:-1;chr7:105607885-105617885:-1;chr7:105668230-105678230:1;chr7:127545620-127555620:1;chr7:127570686-127580686:-1;chr7:145249542-145259542:1;chr7:145712487-145722487:-1;chr8:37595380-37605380:-1;chr8:39913897-39923897:1;chr8:42334194-42344194:-1;chr8:50651925-50661925:-1;chr8:53445822-53455822:1;chr8:56052281-56062281:-1;chr8:56173159-56183159:1;chr8:59017974-59027974:-1;chr8:59145377-59155377:1;chr8:71017020-71027020:-1;chr8:77593047-77603047:-1;chr8:125612834-125622834:-1;chr8:126437506-126447506:-1;chr8:128724200-128734200:1;chr8:141416204-141426204:1;chr8:141660459-141670459:-1;chr8:146116950-146126950:1;chr9:13046915-13056915:-1;chr10:2457205-2467205:-1;chr10:5849505-5859505:1;chr10:5976733-5986733:1;chr11:420288-430288:1;chr11:13765712-13775712:-1;chr11:13845835-13855835:1;chr11:14236525-14246525:-1;chr11:14266598-14276598:-1;chr11:14605355-14615355:1;chr11:14829917-14839917:1;chr11:15420516-15430516:1;chr11:15440576-15450576:-1;chr11:16077676-16087676:1;chr11:16133221-16143221:1;chr11:16408772-16418772:-1;chr11:17040485-17050485:1;chr11:18040184-18050184:-1;chr11:18112431-18122431:1;chr11:18719154-18729154:-1;chr11:22804550-22814550:1;chr11:24209969-24219969:-1;chr11:24604401-24614401:1;chr11:24746684-24756684:-1;chr11:25649497-25659497:1;chr11:26633694-26643694:-1;chr11:26834542-26844542:1;chr11:127282028-127292028:-1;chr11:129975024-129985024:-1;chr12:6203180-6213180:1;chr12:7785820-7795820:1;chr12:22938762-22948762:1;chr12:25109710-25119710:-1;chr12:31760400-31770400:1;chr12:44513336-44523336:-1;chr12:45192842-45202842:1;chr12:46059970-46069970:-1;chr12:46075128-46085128:1;chr12:56901951-56911951:-1;chr12:65142007-65152007:-1;chr12:71043747-71053747:1;chr12:71792898-71802898:-1;chr12:78581255-78591255:1;chr12:79482308-79492308:-1;chr12:80563330-80573330:1;chr12:87846949-87856949:1;chr12:89518904-89528904:1;chr14:29874443-29884443:1;chr14:29949669-29959669:-1;chr14:43834712-43844712:1;chr14:43850145-43860145:-1;chr14:100792509-100802509:-1;chr14:105449153-105459153:1;chr14:106799007-106809007:-1;chr14:106820839-106830839:1;chr16:4676715-4686715:-1;chr16:35015790-35025790:1;chr16:46457004-46467004:1;chr17:25979864-25989864:-1;chr19:16622827-16632827:-1;chr19:16733918-16743918:1;chr19:37282007-37292007:-1;chr20:47804721-47814721:1;chr21:15482341-15492341:-1;chr21:19557283-19567283:-1;chr21:35710063-35720063:1;chr22:18299203-18309203:-1;chr22:18452999-18462999:1;chr22:41484513-41494513:-1;chr22:41747848-41757848:1;chr22:50689936-50699936:1;chrX:56656485-56666485:1;chrX:125431028-125441028:-1;chrY:17411397-17421397:1;chrY:18015495-18025495:-1;chrY:18942830-18952830:-1;chrY:19286059-19296059:1;chrY:20018908-20028908:1 hs1:147116615-147116893,hs1:147120869-147121148;hs1:212322984-212323212,hs1:212324814-212325001;hs1:234564021-234564282,hs1:234587501-234587954;hs2:32906614-32906917,hs2:32921215-32921425;hs2:53495643-53495909,hs3:126131196-126131471;hs2:154819579-154819814,hs2:154953737-154953946;hs3:31398352-31398601,hs3:31402489-31402661;hs3:115901255-115901491,hs3:116286453-116286709;hs3:116567516-116567777,hs3:117530598-117530834;hs3:119795240-119795433,hs3:119806196-119806413;hs3:123958208-123958550,hs3:125897569-125897980;hs3:123997938-123998202,hs3:126832853-126833249;hs3:126240717-126241097,hs3:185241635-185241979;hs3:127181365-127181806,hs3:177743376-177743682;hs3:127188124-127188433,hs3:182820478-182820770;hs3:160198054-160198358,hs3:162219777-162220118;hs3:161726439-161726752,hs3:161782351-161782640;hs3:161728119-161728359,hs3:162073845-162074313;hs3:163661357-163661625,hs3:172425844-172426098;hs3:164202204-164202394,hs3:164206576-164206831;hs3:166269226-166269543,hs3:173293577-173293874;hs3:169210196-169210462,hs3:171690642-171691018;hs3:169859872-169860081,hs3:172104069-172104266;hs3:174214744-174214934,hs3:174418728-174418925;hs3:174463112-174463359,hs3:174635632-174635965;hs3:178631691-178631980,hs3:178687720-178688119;hs3:182098440-182098807,hs3:182963369-182963690;hs3:182109220-182109542,hs3:182889868-182890125;hs4:59600821-59600946,hs4:184927851-184927946;hs4:84044761-84045021,hs4:116840796-116841065;hs4:84044873-84045123,hs4:84162178-84162552;hs4:84161741-84161997,hs4:154803352-154803608;hs4:84359333-84359570,hs4:115979858-115980341;hs4:84359597-84359883,hs4:118043250-118043482;hs4:84477413-84477555,hs4:155178386-155178573;hs4:84477492-84477686,hs4:155178440-155178691;hs4:84479661-84479823,hs4:118043544-118043740;hs4:84483047-84483278,hs4:154850538-154850707;hs4:84496621-84496896,hs4:155152717-155152939;hs4:116012086-116012265,hs4:118043158-118043386;hs4:116012562-116012950,hs4:118042856-118043116;hs4:116653018-116653183,hs4:154803651-154803842;hs4:154853254-154853461,hs4:155177684-155178052;hs4:155152472-155152688,hs4:155177818-155178051;hs4:190632592-190632818,hs4:190637517-190637776;hs5:160920145-160920290,hs5:160958637-160959021;hs6:54649283-54649511,hs6:54660630-54660905;hs6:129777976-129778124,hs7:151938393-151938572;hs6:151153515-151153707,hs6:151195992-151196189;hs7:70231437-70231669,hs7:70250475-70250888;hs7:127550594-127550950,hs7:127573825-127574116;hs8:3410367-3410521,hs8:3855086-3855465;hs8:3848960-3849118,hs8:4146239-4146401;hs8:29124337-29124588,hs8:34157757-34158243;hs8:34156900-34157260,hs8:37599362-37599654;hs8:39916180-39916432,hs8:42339861-42340109;hs8:53449969-53450322,hs8:56054000-56054224;hs8:56173699-56174038,hs8:59023740-59024126;hs8:56174030-56174244,hs8:59153087-59153248;hs8:60065618-60065884,hs8:60066827-60067171;hs8:61103096-61103253,hs8:70685450-70685603;hs8:73076069-73076345,hs8:73101612-73102006;hs8:75934152-75934462,hs8:76104164-76104464;hs8:100859209-100859399,hs8:100891498-100891755;hs8:135962087-135962286,hs8:135966765-135966972;hs9:21974480-21974842,hs9:21981193-21981411;hs10:90013676-90013967,hs10:90245921-90246263;hs10:99669634-99669883,hs10:110971631-110971877;hs11:424483-424716,hs3:174768296-174768597;hs11:13769189-13769555,hs11:14240046-14240612;hs11:13850674-13850915,hs11:43470462-43470644;hs11:14272326-14272694,hs11:24217820-24218230;hs11:14276049-14276427,hs11:22802119-22802365;hs11:14835031-14835444,hs3:182009695-182010196;hs11:15407484-15407884,hs11:26635866-26636192;hs11:15408813-15409106,hs11:22808256-22808582;hs11:15425846-15426134,hs11:24754435-24754702;hs11:15442781-15443056,hs3:182934393-182934670;hs11:16070906-16071183,hs11:16412552-16412794;hs11:17049109-17049228,hs11:18049658-18049887;hs11:17049388-17049498,hs11:18049622-18049767;hs11:25000840-25001123,hs11:25003130-25003399;hs11:32707525-32707776,hs11:32715488-32715793;hs11:56550882-56551027,hs11:127297241-127297475;hs11:129987869-129988096,hs3:182812700-182812941;hs11:131603981-131604170,hs3:182964962-182965423;hs11:131756092-131756374,hs11:134236417-134236711;hs12:6222171-6222357,hs12:6441368-6441530;hs12:22945181-22945426,hs12:80564796-80565150;hs12:25113772-25113952,hs12:79488413-79488678;hs12:31765486-31765728,hs12:46062949-46063503;hs12:31929150-31929351,hs12:71050764-71051001;hs12:31929160-31929268,hs12:71795623-71795796;hs12:44517686-44517894,hs12:78583198-78583511;hs12:45198059-45198304,hs12:47845314-47845547;hs12:46081307-46081591,hs12:89514608-89514883;hs12:47846716-47847037,hs12:82128630-82128883;hs12:71718780-71719086,hs12:89522051-89522305;hs12:83268915-83269149,hs12:83270850-83271188;hs14:29880573-29880832,hs14:29952766-29953033;hs14:59220384-59220521,hs8:88688080-88688253;hs14:59220570-59220878,hs9:89303933-89304264;hs16:15131713-15131838,hs6:74354076-74354222;hs19:19695771-19695978,hs19:19701206-19701395;hs19:53201204-53201356,hs19:53206671-53206839;hs20:14798890-14799174,hs20:14817122-14817355;hs20:26080353-26080607,hs20:26083819-26084055;hs21:11034795-11035027,hs6:129777976-129778128;hs21:20406646-20406806,hs3:87421664-87421790;hs21:20407363-20407632,hs3:87421650-87421770;hs22:29065615-29065887,hs8:112346293-112346590;hsX:36852059-36852313,hsX:36855120-36855339;hsX:125361769-125361992,hsX:125438102-125438340 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22903, USA Tumor genomes are generally thought to evolve through a gradual accumulation of mutations, but the observation that extraordinarily complex rearrangements can arise through single mutational events suggests that evolution may be accelerated by punctuated changes in genome architecture. To assess the prevalence and origins of complex genomic rearrangements (CGRs), we mapped 6179 somatic structural variation breakpoints in 64 cancer genomes from seven tumor types and screened for clusters of three or more interconnected breakpoints. We find that complex breakpoint clusters are extremely common: 154 clusters comprise 25% of all somatic breakpoints, and 75% of tumors exhibit at least one complex cluster. Based on copy number state profiling, 63% of breakpoint clusters are consistent with being CGRs that arose through a single mutational event. CGRs have diverse architectures including focal breakpoint clusters, large-scale rearrangements joining clusters from one or more chromosomes, and staggeringly complex chromothripsis events. Notably, chromothripsis has a significantly higher incidence in glioblastoma samples (39%) relative to other tumor types (9%). Chromothripsis breakpoints also show significantly elevated intra-tumor allele frequencies relative to simple SVs, which indicates that they arise early during tumorigenesis or confer selective advantage. Finally, assembly and analysis of 4002 somatic and 6982 germline breakpoint sequences reveal that somatic breakpoints show significantly less microhomology and fewer templated insertions than germline breakpoints, and this effect is stronger at CGRs than at simple variants. These results are inconsistent with replication-based models of CGR genesis and strongly argue that nonhomologous repair of concurrently arising DNA double-strand breaks is the predominant mechanism underlying complex cancer genome rearrangements. GRCh37/hg19 Yes NA CTDB0237 Research 21349919 Kloosterman WP, Guryev V, van Roosmalen M, Duran KJ, de Bruijn E, Bakker SC, Letteboer T, van Nesselrooij B, Hochstenbach R, Poot M, Cuppen E Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline Human Molecular Genetics 2011 May 1,4,10 Congenital abnormality Next Generation Sequencing Homo sapiens Child AB SOLiD V3.5 chr10:100494193-100495449:1;chr10:103614093-103615843:1;chr10:108027167-108035581:-1;chr10:111569251-111581023:-1;chr10:114109926-114119303:-1;chr10:121306076-121307348:1;chr10:122223949-122232015:-1;chr10:12557884-12565926:-1;chr10:127190794-127196789:1;chr10:127190916-127200038:-1;chr10:127196299-127198008:1;chr10:127582158-127591842:-1;chr10:129594867-129596142:1;chr10:130261512-130262835:1;chr10:131879057-131881003:1;chr10:13256585-13263388:-1;chr10:132973775-132975538:1;chr10:133730165-133735717:-1;chr10:134176880-134178279:1;chr10:134632432-134641010:-1;chr10:135288409-135296723:-1;chr10:1580844-1588085:-1;chr10:1739075-1746093:-1;chr10:19993530-20000841:-1;chr10:20847848-20863002:-1;chr10:21682208-21689448:-1;chr10:24374530-24381199:-1;chr10:26878362-26940492:1;chr10:26996602-27004744:-1;chr10:31440462-31447416:-1;chr10:35898846-35900692:1;chr10:35954997-35957074:1;chr10:38776277-38785789:1;chr10:38811055-38818734:1;chr10:39116420-39152577:1;chr10:39120486-39140233:1;chr10:42355091-42411674:1;chr10:42360556-42374891:-1;chr10:42365146-42382467:-1;chr10:42380941-42398771:-1;chr10:42382806-42392985:-1;chr10:42384236-42385486:1;chr10:42384258-42397248:-1;chr10:42384686-42385547:1;chr10:42385038-42385233:1;chr10:42385150-42385682:1;chr10:42387283-42388092:1;chr10:42387817-42397144:-1;chr10:42390816-42392037:1;chr10:42392696-42393449:1;chr10:42392716-42396890:-1;chr10:42396117-42396890:1;chr10:42397820-42409218:-1;chr10:42398374-42399700:1;chr10:42398535-42408253:-1;chr10:42399266-42400353:1;chr10:42399447-42400404:1;chr10:42525859-42535485:-1;chr10:42527237-42539747:1;chr10:42529288-42530627:1;chr10:42596723-42600356:1;chr10:42596801-42666907:-1;chr10:42596879-42667525:1;chr10:42660114-42668959:-1;chr10:42699402-42718997:-1;chr10:4287042-4294700:-1;chr10:445633-452525:-1;chr10:4706145-4713575:-1;chr10:51001024-51013627:-1;chr10:5210384-5211992:1;chr10:54013456-54020917:-1;chr10:5887968-5895122:-1;chr10:59206886-59213950:-1;chr10:6408910-6420429:-1;chr10:65506341-65513870:-1;chr10:66395793-66404146:-1;chr10:7074133-7081360:-1;chr10:71278071-71294091:-1;chr10:78252746-78263410:-1;chr10:78344152-78354978:-1;chr10:94131771-94140430:-1;chr10:99032179-99040282:-1;chr11:102600228-102602171:1;chr11:10289672-10296863:-1;chr11:103914158-103920606:-1;chr11:104265130-104276004:-1;chr11:104938040-104975662:-1;chr11:104944236-104981027:-1;chr11:11376743-11383623:-1;chr11:114422187-114433221:-1;chr11:119997770-120005047:-1;chr11:121199127-121200852:1;chr11:122344768-122352603:-1;chr11:124248695-124269597:-1;chr11:126145387-126146995:1;chr11:127747025-127754392:-1;chr11:129013162-129018345:-1;chr11:132896828-132898645:1;chr11:134598992-134609873:-1;chr11:134720726-134722397:1;chr11:134794133-134801420:-1;chr11:1449036-1455934:-1;chr11:15379333-15381154:1;chr11:1690786-1692475:1;chr11:18165383-18199296:1;chr11:1912462-1939769:-1;chr11:21844589-21851953:-1;chr11:24347136-24358031:-1;chr11:29004316-29015447:-1;chr11:30949282-30951052:1;chr11:3117192-3118968:1;chr11:33669643-33670910:1;chr11:36330195-36331783:1;chr11:38811774-38813563:1;chr11:41830785-41832724:1;chr11:48365621-48376288:-1;chr11:48598329-48607205:-1;chr11:48732073-48739573:-1;chr11:4965367-4980808:-1;chr11:51567239-51580943:-1;chr11:51567285-51584998:1;chr11:51572136-51586187:-1;chr11:51575665-51593196:-1;chr11:5267593-5278280:-1;chr11:5269509-5276233:1;chr11:54794248-54802634:1;chr11:5518677-5525776:-1;chr11:55431709-55445809:1;chr11:5757456-5765232:-1;chr11:58101885-58119134:-1;chr11:59049392-59050944:1;chr11:66709899-66715678:-1;chr11:70216362-70217576:1;chr11:7132424-7139018:-1;chr11:76888255-76890132:1;chr11:7788866-7794794:-1;chr11:81497917-81523674:-1;chr11:8179537-8180887:1;chr11:92867289-92878654:-1;chr11:93676671-93684026:-1;chr11:93967759-93972140:1;chr11:995130-996539:1;chr12:100286462-100293433:-1;chr12:10572909-10597619:1;chr12:11166784-11226227:1;chr12:11189879-11250016:1;chr12:116851827-116860510:1;chr12:117639432-117646065:-1;chr12:1191775-1201666:-1;chr12:123181208-123195709:1;chr12:129227342-129235675:-1;chr12:130339002-130345600:-1;chr12:132877783-132884601:-1;chr12:16417118-16424045:-1;chr12:1683224-1684357:1;chr12:2363957-2365185:1;chr12:2364963-2366088:1;chr12:25498850-25500530:1;chr12:2791443-2792833:1;chr12:29953309-29962708:-1;chr12:33293501-33310545:-1;chr12:34834267-34842113:1;chr12:34837637-34854188:1;chr12:34838937-34850913:-1;chr12:37988214-37997271:-1;chr12:38007724-38020741:-1;chr12:38082228-38089077:-1;chr12:43974230-43982488:-1;chr12:45900218-45912840:-1;chr12:52839780-52869079:-1;chr12:52841684-52867755:1;chr12:54657692-54664058:-1;chr12:60519263-60527629:-1;chr12:6413713-6415327:1;chr12:66525014-66532780:-1;chr12:70592081-70599997:-1;chr12:71599341-71607514:-1;chr12:72353978-72361092:-1;chr12:80154922-80162694:1;chr12:84590596-84598862:-1;chr12:8556457-8593436:-1;chr12:86423673-86436256:-1;chr12:96008217-96014968:-1;chr12:96230347-96239243:-1;chr12:96337382-96345777:-1;chr12:99791335-99805029:-1;chr13:101103407-101104751:1;chr13:101891834-101899045:-1;chr13:110469725-110483760:-1;chr13:113526537-113528194:1;chr13:19326179-19350569:-1;chr13:20822666-20831350:-1;chr13:23629867-23639977:-1;chr13:27047414-27054853:-1;chr13:27546100-27547875:1;chr13:31639840-31641688:1;chr13:36324534-36325774:1;chr13:36530433-36532410:1;chr13:36531407-36532902:1;chr13:38069319-38088280:-1;chr13:39054736-39063049:-1;chr13:39931469-39938586:-1;chr13:43536542-43544208:-1;chr13:50192573-50199728:-1;chr13:51066221-51077285:-1;chr13:79258751-79260385:1;chr13:83163102-83174889:-1;chr13:85798255-85806057:-1;chr13:90860630-90867725:-1;chr13:97990550-97991747:1;chr13:99251451-99261213:-1;chr14:100418604-100419949:1;chr14:101338930-101340223:1;chr14:104361941-104363886:1;chr14:106071578-106123607:-1;chr14:106079220-106106161:-1;chr14:106081511-106102543:1;chr14:106192741-106228212:-1;chr14:106445842-106453640:-1;chr14:106716799-106728803:1;chr14:106778205-106810902:-1;chr14:106780279-106812260:1;chr14:106783663-106814179:-1;chr14:106794112-106825092:1;chr14:106850116-106936906:-1;chr14:106854243-106938941:1;chr14:106855563-106942261:-1;chr14:107080216-107099302:-1;chr14:107082485-107099168:1;chr14:107160555-107161723:1;chr14:107161674-107162810:1;chr14:20548285-20557634:-1;chr14:21346373-21416044:-1;chr14:24440863-24488266:-1;chr14:24443388-24485764:1;chr14:27764185-27766146:1;chr14:35505639-35512438:-1;chr14:35602588-35617672:-1;chr14:40095945-40102597:-1;chr14:40607034-40621488:-1;chr14:42985376-42995400:-1;chr14:60338587-60346073:-1;chr14:65357486-65366676:-1;chr14:66257193-66258873:1;chr14:70014357-70024402:-1;chr14:73760505-73762165:1;chr14:80103464-80117993:-1;chr14:82496118-82506427:-1;chr14:83586573-83588043:1;chr14:89177025-89178418:1;chr14:95088388-95095246:-1;chr15:100463846-100471167:-1;chr15:100930237-100931882:1;chr15:101091838-101100977:-1;chr15:20578525-20592246:-1;chr15:22334022-22347181:-1;chr15:22370266-22386442:-1;chr15:24406449-24485046:1;chr15:25113942-25121477:-1;chr15:25928276-25934976:-1;chr15:29422799-29424569:1;chr15:29850095-29851706:1;chr15:34112423-34113911:1;chr15:34637828-34639227:1;chr15:40853416-40854999:1;chr15:41853406-41871118:-1;chr15:55215665-55227633:-1;chr15:62550757-62552920:1;chr15:63264691-63271969:-1;chr15:63641825-63684653:-1;chr15:65813281-65821801:-1;chr15:68423114-68431866:-1;chr15:72383588-72390746:-1;chr15:74508287-74509728:1;chr15:76882480-76899764:-1;chr15:77991064-77992476:1;chr15:77991794-77993079:1;chr15:83548976-83560931:-1;chr15:84538538-84547055:-1;chr15:86556032-86557230:1;chr15:91979081-91985465:-1;chr15:92672122-92680067:-1;chr16:1075357-1076482:1;chr16:1420546-1426646:-1;chr16:18830761-18841475:-1;chr16:23044984-23052282:-1;chr16:23758005-23764547:-1;chr16:23786719-23788025:1;chr16:25337388-25345762:-1;chr16:26385035-26386697:1;chr16:27952093-27953356:1;chr16:32454546-32457137:1;chr16:32529355-32536233:-1;chr16:32597428-32604520:-1;chr16:33370978-33381916:-1;chr16:33866361-33876234:1;chr16:33952852-33958475:1;chr16:33953581-33960939:-1;chr16:33971374-33977683:1;chr16:33973683-33982373:-1;chr16:34180692-34195345:1;chr16:35180903-35200990:-1;chr16:35247266-35252324:1;chr16:46385802-46415983:1;chr16:46385806-46415528:-1;chr16:46385810-46404999:-1;chr16:46385811-46410316:-1;chr16:46385818-46396815:-1;chr16:46388097-46389246:1;chr16:46388411-46415575:-1;chr16:46389081-46402586:-1;chr16:46389230-46410697:-1;chr16:46391263-46408646:-1;chr16:46392020-46401355:-1;chr16:46394446-46406579:-1;chr16:46398423-46409175:-1;chr16:46401799-46414354:-1;chr16:46407371-46416281:-1;chr16:46414027-46455248:1;chr16:46416734-46431905:-1;chr16:46416846-46453807:1;chr16:46416903-46436119:-1;chr16:46425467-46500280:1;chr16:46426279-46501915:-1;chr16:57722651-57729441:-1;chr16:70975161-70982230:-1;chr16:71417773-71419364:1;chr16:76535985-76546990:-1;chr16:77087987-77095380:-1;chr16:78368954-78387032:-1;chr16:8105565-8112273:-1;chr16:84499212-84507367:-1;chr16:867858-869346:1;chr16:88110503-88118185:-1;chr17:1209842-1217142:-1;chr17:134522-140659:-1;chr17:14186859-14194535:-1;chr17:15786788-15796443:-1;chr17:1641031-1646714:-1;chr17:18915950-18917589:1;chr17:191864-199288:-1;chr17:21210259-21223588:-1;chr17:21318789-21325301:-1;chr17:22244722-22262811:1;chr17:22244728-22261598:-1;chr17:22249719-22262755:-1;chr17:25263183-25267790:1;chr17:26777529-26786749:-1;chr17:35752931-35761038:-1;chr17:39419106-39435006:-1;chr17:39532402-39539228:1;chr17:40703867-40708386:1;chr17:41381671-41402241:-1;chr17:45212876-45235622:-1;chr17:45213103-45249331:-1;chr17:46166172-46167907:1;chr17:47296-49284:1;chr17:47349149-47355837:-1;chr17:51850428-51862294:-1;chr17:61959955-61983596:1;chr17:71047019-71048551:1;chr17:72728781-72730438:1;chr17:77478487-77480412:1;chr17:78460086-78465662:-1;chr17:78902957-78904548:1;chr18:106091-112255:1;chr18:106902-108383:1;chr18:108186-109285:1;chr18:108284-109301:1;chr18:13261047-13262428:1;chr18:14259059-14314176:1;chr18:14277663-14304287:-1;chr18:15387006-15391786:-1;chr18:15404570-15410574:1;chr18:18510935-18520301:1;chr18:18510940-18517930:-1;chr18:18516123-18517180:1;chr18:18518086-18519675:1;chr18:18519264-18520297:1;chr18:21901137-21907016:-1;chr18:21988678-21994759:-1;chr18:3036212-3037713:1;chr18:38256941-38269565:-1;chr18:38861768-38871152:-1;chr18:47692508-47701142:-1;chr18:54944214-54951963:-1;chr18:59669150-59676675:-1;chr18:60884852-60886872:1;chr18:63720851-63734901:-1;chr18:63764436-63771586:-1;chr18:64216810-64224315:-1;chr18:71871435-71872692:1;chr18:74102263-74109137:-1;chr18:74678232-74679846:1;chr18:75379143-75385232:-1;chr18:76126775-76135744:-1;chr18:76199249-76206136:-1;chr18:76959824-76961124:1;chr18:76960694-76961512:1;chr18:77301169-77302538:1;chr18:77308387-77314451:-1;chr19:1141378-1143013:1;chr19:12691613-12701692:-1;chr19:14705710-14707691:1;chr19:14729901-14736448:-1;chr19:15044095-15052355:-1;chr19:21901022-21908183:-1;chr19:23138222-23145500:-1;chr19:23461987-23469796:-1;chr19:23803460-23810292:-1;chr19:24052275-24151057:-1;chr19:24155603-24156767:1;chr19:27731777-27733045:1;chr19:27731811-27740545:1;chr19:27731898-27740520:-1;chr19:27732043-27732984:1;chr19:27732156-27733084:1;chr19:27732184-27733310:1;chr19:27732740-27733326:1;chr19:27737451-27738580:1;chr19:27737921-27738657:1;chr19:27829041-27839268:-1;chr19:27869407-27875767:-1;chr19:27958331-27965710:-1;chr19:29947609-29958962:-1;chr19:30385520-30395402:-1;chr19:31284592-31292097:-1;chr19:3170051-3177524:-1;chr19:33948731-33950503:1;chr19:35848488-35865976:-1;chr19:37512262-37519040:-1;chr19:4035008-4036580:1;chr19:40609961-40618616:-1;chr19:41444881-41519190:-1;chr19:43828353-43833408:1;chr19:51404023-51410250:-1;chr19:52131518-52152108:-1;chr19:52173058-52179758:-1;chr19:53093661-53100631:-1;chr19:53419285-53427350:-1;chr19:53686292-53695044:-1;chr19:53929796-54017154:1;chr19:53933676-53978286:-1;chr19:54728665-54747022:1;chr19:54798418-54809767:-1;chr19:54860714-54862226:1;chr19:55248192-55284944:-1;chr19:55250263-55273995:-1;chr19:55331168-55371962:-1;chr19:55335502-55370490:1;chr19:55776979-55778713:1;chr19:56223646-56224811:1;chr19:56265828-56282824:-1;chr19:56269162-56284486:1;chr19:56270754-56287854:-1;chr19:6069501-6071051:1;chr19:6625662-6626809:1;chr19:6994699-6996431:1;chr19:7515268-7515879:1;chr19:8408739-8416791:-1;chr1:1009848-1016970:-1;chr1:108265400-108267027:1;chr1:109571739-109577428:-1;chr1:110184552-110193326:-1;chr1:11030634-11031834:1;chr1:112832397-112840390:-1;chr1:113609112-113616309:-1;chr1:116227103-116235611:-1;chr1:120110510-120153678:1;chr1:120126849-120159403:1;chr1:121351777-121359140:1;chr1:121351921-121360194:-1;chr1:121475033-121485401:1;chr1:121484053-121485384:1;chr1:121484389-121485396:1;chr1:121484453-121485385:1;chr1:121484510-121485393:1;chr1:121484607-121485393:1;chr1:121484664-121485384:1;chr1:121484726-121485395:1;chr1:121484786-121485393:1;chr1:121484863-121485377:1;chr1:121484926-121485393:1;chr1:121484995-121485396:1;chr1:121485077-121485357:1;chr1:121485130-121485385:1;chr1:121485144-121485397:1;chr1:121485198-121485384:1;chr1:121485214-121485397:1;chr1:121485293-121485393:1;chr1:142535452-142542340:1;chr1:14434136-14441642:-1;chr1:144893394-144909222:-1;chr1:145089801-145100029:-1;chr1:152553397-152590497:-1;chr1:152757388-152773867:-1;chr1:156523700-156531800:-1;chr1:1581111-1652617:1;chr1:1581119-1649849:-1;chr1:158864663-158872769:-1;chr1:159010029-159020437:-1;chr1:1591623-1663058:-1;chr1:1596461-1666245:1;chr1:160932778-160942203:-1;chr1:161480901-161569609:-1;chr1:161482466-161564560:1;chr1:161492934-161581939:1;chr1:161506227-161597319:1;chr1:161508527-161596714:-1;chr1:161526990-161612072:1;chr1:161535684-161620280:1;chr1:161562439-161647351:-1;chr1:16358427-16385680:1;chr1:165860917-165862279:1;chr1:168378812-168380561:1;chr1:16903094-16917074:-1;chr1:16907818-16916051:1;chr1:16908064-16920437:-1;chr1:16943203-16949792:-1;chr1:17008182-17015120:-1;chr1:178974738-178982956:-1;chr1:18015180-18016626:1;chr1:184812082-184823977:-1;chr1:187462360-187469247:-1;chr1:187712831-187725655:-1;chr1:193466296-193467565:1;chr1:194448563-194456338:-1;chr1:194573159-194580723:-1;chr1:196728786-196814303:1;chr1:196730772-196822296:-1;chr1:196735803-196820180:1;chr1:197497945-197505865:-1;chr1:198770680-198777940:-1;chr1:199436053-199443187:-1;chr1:203681886-203688920:-1;chr1:207539444-207548979:-1;chr1:210075691-210087017:-1;chr1:210826482-210827742:1;chr1:210827262-210828434:1;chr1:212468277-212475906:-1;chr1:213082104-213088858:-1;chr1:220076986-220078350:1;chr1:222371132-222383058:-1;chr1:22300577-22332752:-1;chr1:22300788-22329341:1;chr1:22308016-22337631:-1;chr1:22903511-22905133:1;chr1:229810165-229823911:-1;chr1:232456015-232462552:-1;chr1:236260432-236261300:1;chr1:236546060-236553331:-1;chr1:23718026-23719921:1;chr1:239575083-239575922:1;chr1:24517758-24526775:-1;chr1:246135210-246141942:-1;chr1:246680570-246687530:-1;chr1:246948176-246949214:1;chr1:247847246-247859777:-1;chr1:248048734-248060070:-1;chr1:25155408-25164657:-1;chr1:26457716-26466929:-1;chr1:27412158-27414006:1;chr1:31123457-31125100:1;chr1:31127600-31129304:1;chr1:33651534-33653153:1;chr1:42009489-42011032:1;chr1:42483301-42484852:1;chr1:4998231-4999697:1;chr1:53590884-53597920:-1;chr1:55089987-55098506:-1;chr1:56827726-56837815:-1;chr1:6037071-6038720:1;chr1:63702375-63711156:-1;chr1:66021860-66032943:-1;chr1:72763641-72814829:-1;chr1:73449670-73458113:1;chr1:7579597-7580932:1;chr1:83123467-83130280:-1;chr1:84515009-84527113:-1;chr1:87511927-87513037:1;chr1:89473019-89481774:-1;chr1:94285628-94293639:-1;chr1:9470299-9472186:1;chr20:1386217-1393495:-1;chr20:1558290-1597556:-1;chr20:20317018-20318706:1;chr20:21283327-21291104:-1;chr20:2216059-2217897:1;chr20:23700282-23783569:1;chr20:23716249-23795189:1;chr20:23717527-23800044:-1;chr20:26295206-26305181:-1;chr20:29506461-29538444:-1;chr20:29583056-29594300:-1;chr20:29636035-29642251:-1;chr20:31307731-31314782:-1;chr20:32813423-32822105:-1;chr20:33239380-33245759:-1;chr20:35023783-35025503:1;chr20:37717334-37718824:1;chr20:39904932-39909945:-1;chr20:42021836-42028408:-1;chr20:42269191-42276622:-1;chr20:43303800-43311509:-1;chr20:45417010-45418819:1;chr20:5267825-5269327:1;chr20:54431975-54443481:-1;chr20:56771232-56772872:1;chr20:56990594-56992425:1;chr20:59905818-59907358:1;chr20:7093677-7105125:-1;chr21:10698334-10707263:1;chr21:10714992-10729425:1;chr21:10743184-10752863:-1;chr21:10753781-10761163:-1;chr21:10774461-10812159:1;chr21:10775631-10796014:1;chr21:10785094-10802138:1;chr21:10797973-10810664:-1;chr21:10832812-10856865:1;chr21:11079519-11120087:-1;chr21:11086958-11094486:-1;chr21:11094415-11111008:-1;chr21:11102399-11109180:-1;chr21:11186190-11188053:1;chr21:15238367-15260370:1;chr21:15243498-15273003:1;chr21:15248241-15271008:1;chr21:16586118-16594195:-1;chr21:20057409-20080900:1;chr21:23259481-23261062:1;chr21:33401934-33403528:1;chr21:34204990-34206216:1;chr21:42954234-43007296:-1;chr21:44005057-44012945:-1;chr21:44133043-44142441:-1;chr21:44967515-44976544:-1;chr21:46643677-46645310:1;chr21:47385403-47392059:-1;chr21:47654576-47662030:-1;chr21:47799159-47807490:-1;chr21:9848712-9856247:-1;chr22:17766761-17781909:-1;chr22:18055335-18063155:-1;chr22:18878275-18886663:-1;chr22:18878281-18884395:1;chr22:20947882-20956699:-1;chr22:22675545-22762960:-1;chr22:22703376-22752524:1;chr22:23014341-23086247:-1;chr22:23475491-23482831:-1;chr22:24271453-24314231:-1;chr22:27164875-27172567:-1;chr22:32575089-32576439:1;chr22:33753459-33762744:-1;chr22:33777689-33785452:-1;chr22:37140416-37150539:-1;chr22:38584277-38585870:1;chr22:39291721-39301235:-1;chr22:42718795-42720793:1;chr22:44506138-44513976:-1;chr22:47774437-47775754:1;chr22:49424691-49426513:1;chr2:100101136-100107623:-1;chr2:10151697-10158020:-1;chr2:109307674-109314825:-1;chr2:109687366-109697908:-1;chr2:11093878-11095539:1;chr2:112008412-112009578:1;chr2:114148350-114155941:-1;chr2:116375785-116377596:1;chr2:1216291-1228798:-1;chr2:124439418-124441062:1;chr2:126365967-126372692:-1;chr2:126440196-126454970:-1;chr2:127671939-127680157:-1;chr2:129636030-129649057:-1;chr2:132996310-133003315:1;chr2:133021974-133031242:-1;chr2:133024091-133030660:1;chr2:133025781-133025872:1;chr2:133026136-133027824:1;chr2:133669693-133677533:-1;chr2:134964119-134973204:-1;chr2:147020007-147021894:1;chr2:1529610-1539006:1;chr2:153793086-153802294:-1;chr2:154892878-154901990:-1;chr2:159956244-159963837:-1;chr2:160146122-160154112:-1;chr2:162135186-162139129:1;chr2:162329670-162336452:-1;chr2:16268067-16276940:-1;chr2:166012407-166019649:-1;chr2:170639010-170645897:-1;chr2:173001549-173010041:-1;chr2:176344126-176355704:-1;chr2:177262857-177275108:-1;chr2:181885493-181887051:1;chr2:1864596-1866513:1;chr2:189117017-189123643:-1;chr2:194686867-194701904:-1;chr2:194922653-194923935:1;chr2:202144226-202151691:-1;chr2:203896276-203906762:-1;chr2:208472403-208479235:-1;chr2:209940427-209951496:-1;chr2:21152285-21179425:-1;chr2:217086925-217095526:-1;chr2:220049983-220058329:-1;chr2:221502854-221504526:1;chr2:222228361-222235487:-1;chr2:223757438-223765329:-1;chr2:227579592-227581370:1;chr2:229261954-229271425:-1;chr2:235552631-235559615:-1;chr2:242743974-242750285:-1;chr2:242829387-242830353:1;chr2:242944032-242953134:-1;chr2:31722643-31729534:-1;chr2:32047728-32049372:1;chr2:33089238-33097586:-1;chr2:33138809-33146213:-1;chr2:34521008-34528551:-1;chr2:34693005-34739244:-1;chr2:35973780-36000245:-1;chr2:36214859-36221114:-1;chr2:38938194-38939701:1;chr2:396903-402680:-1;chr2:41970124-41979078:-1;chr2:4778046-4790030:-1;chr2:48778853-48787406:-1;chr2:52746963-52787882:-1;chr2:54562619-54570189:-1;chr2:71844954-71846729:1;chr2:73846016-73918308:1;chr2:73854907-73921425:-1;chr2:73867095-73932123:-1;chr2:76523709-76531502:-1;chr2:76770445-76777979:-1;chr2:89026172-89034823:-1;chr2:89850267-89859235:-1;chr2:89874590-89878632:1;chr2:89874762-89882012:-1;chr2:90477791-90484325:1;chr2:92269070-92291250:1;chr2:92269319-92309784:1;chr2:92272945-92321070:-1;chr2:92272959-92323556:1;chr2:92279380-92323363:-1;chr2:92280743-92306501:-1;chr2:92280746-92297954:-1;chr2:92281274-92320416:1;chr2:92286736-92312166:-1;chr2:92286737-92324694:1;chr2:92287715-92300698:-1;chr2:92287739-92317735:-1;chr2:92287739-92325029:-1;chr2:92290176-92307536:-1;chr2:92295848-92309621:-1;chr2:92295857-92322042:-1;chr2:92295890-92306080:-1;chr2:92296263-92309689:-1;chr2:92300659-92320107:-1;chr2:92305376-92320415:-1;chr2:92305403-92306838:1;chr2:92305657-92325025:-1;chr2:92315393-92324733:1;chr2:92315393-92324750:-1;chr3:125312804-125323113:-1;chr3:125669800-125678402:-1;chr3:128376459-128406679:-1;chr3:129760749-129809984:-1;chr3:130344862-130355452:-1;chr3:133501263-133506552:-1;chr3:136018290-136028695:-1;chr3:13996735-13998442:1;chr3:146382466-146392692:-1;chr3:148278456-148288060:-1;chr3:152309323-152316050:-1;chr3:152610623-152612071:1;chr3:155479659-155513431:1;chr3:162714846-162726115:-1;chr3:162762280-162771427:-1;chr3:176192048-176200629:-1;chr3:1779412-1790628:-1;chr3:186578191-186588160:-1;chr3:187730188-187738016:-1;chr3:189734696-189743334:-1;chr3:189958750-189960296:1;chr3:192872798-192887976:-1;chr3:194395945-194403095:-1;chr3:195437433-195438972:1;chr3:195510687-195517453:-1;chr3:197108771-197120913:-1;chr3:197841971-197853017:-1;chr3:21007082-21015589:-1;chr3:22089394-22100389:-1;chr3:25028001-25034265:-1;chr3:26447852-26455189:-1;chr3:32099287-32110486:-1;chr3:3231311-3233115:1;chr3:32803471-32810546:-1;chr3:38125764-38127065:1;chr3:4064335-4072059:-1;chr3:42835477-42843467:-1;chr3:47488035-47496300:-1;chr3:53024449-53041619:-1;chr3:65185985-65217786:-1;chr3:67490741-67499630:-1;chr3:68008655-68010343:1;chr3:68736477-68750657:-1;chr3:80923255-80929834:-1;chr3:81592680-81602254:-1;chr3:8322768-8329532:-1;chr3:83850660-83858150:-1;chr3:95462839-95470802:-1;chr3:97873485-97930079:1;chr3:98408477-98417023:-1;chr3:98896326-98904811:-1;chr4:10208157-10237274:-1;chr4:103326854-103334871:-1;chr4:105026699-105037389:-1;chr4:107053877-107066055:-1;chr4:108124996-108134772:-1;chr4:108274008-108282151:-1;chr4:115172467-115186515:-1;chr4:130064011-130070611:-1;chr4:133178194-133185305:-1;chr4:135431019-135438545:-1;chr4:138176433-138178196:1;chr4:139466041-139475877:-1;chr4:142228145-142236638:-1;chr4:146436501-146443218:-1;chr4:146916557-146930235:-1;chr4:162446527-162454690:-1;chr4:163391337-163399702:-1;chr4:166000319-166007599:-1;chr4:167674499-167685342:-1;chr4:171068858-171075858:-1;chr4:172985878-172995769:-1;chr4:173422132-173436391:-1;chr4:18161612-18163433:1;chr4:181873737-181881298:-1;chr4:183750725-183757564:-1;chr4:184652769-184661696:-1;chr4:186438730-186446953:-1;chr4:187350936-187360191:-1;chr4:187878537-187894516:-1;chr4:189363953-189371291:-1;chr4:190054509-190067258:-1;chr4:190189103-190202750:-1;chr4:190226387-190232337:-1;chr4:190478172-190478975:1;chr4:190510737-190511936:1;chr4:190511006-190512279:1;chr4:190533170-190541357:-1;chr4:190602939-190612050:-1;chr4:190605217-190613080:-1;chr4:190659005-190660560:1;chr4:190677966-190685271:-1;chr4:190754583-190761191:-1;chr4:19076414-19088359:-1;chr4:190796194-190804344:-1;chr4:190802440-190803384:1;chr4:190882989-190894211:-1;chr4:21158173-21169486:-1;chr4:22073355-22080270:-1;chr4:26287484-26297909:-1;chr4:29320762-29322561:1;chr4:33846938-33859399:-1;chr4:3609847-3621073:-1;chr4:40022197-40028504:-1;chr4:42760736-42771849:-1;chr4:46052883-46061395:-1;chr4:49093343-49158524:1;chr4:49101047-49114173:1;chr4:49104621-49123083:1;chr4:49105931-49151840:-1;chr4:49121026-49151784:-1;chr4:49145438-49158450:1;chr4:49313858-49326202:1;chr4:49512341-49517870:1;chr4:49633409-49660017:1;chr4:547915-549429:1;chr4:55035095-55036818:1;chr4:6035134-6036187:1;chr4:61327348-61335648:-1;chr4:61936436-61945167:-1;chr4:62366-68636:-1;chr4:63667658-63679113:-1;chr4:66808146-66809687:1;chr4:68264228-68266742:1;chr4:68265521-68266604:1;chr4:6894328-6902467:-1;chr4:69440285-69542298:-1;chr4:70465568-70475380:-1;chr4:736289-743667:-1;chr4:75639996-75651361:-1;chr4:79266185-79278518:-1;chr4:80357773-80365818:-1;chr4:80884934-80896731:-1;chr4:82926286-82934132:-1;chr4:8796832-8820205:-1;chr4:88265263-88276666:-1;chr4:88481584-88488125:-1;chr4:90556330-90566300:-1;chr4:91594105-91605874:-1;chr4:93567359-93569832:1;chr4:9454349-9484007:-1;chr4:94556952-94568469:-1;chr5:1019657-1029259:-1;chr5:10270806-10277934:-1;chr5:103399689-103406020:1;chr5:103852057-103863249:-1;chr5:106322311-106329132:-1;chr5:108592038-108603580:-1;chr5:112481094-112482600:1;chr5:113323889-113339377:-1;chr5:114753722-114760829:-1;chr5:119377008-119385198:-1;chr5:121573414-121583295:-1;chr5:121611763-121711928:1;chr5:12808014-12823096:-1;chr5:132916616-132927764:-1;chr5:133132096-133139052:-1;chr5:1333518-1334663:1;chr5:135113217-135123271:-1;chr5:136851709-136858882:-1;chr5:137019707-137026412:-1;chr5:140219728-140241458:-1;chr5:140554266-140559209:1;chr5:151453681-151464784:-1;chr5:155136996-155190029:-1;chr5:156083116-156095423:-1;chr5:160586224-160592619:-1;chr5:163662327-163669217:-1;chr5:164138939-164146494:-1;chr5:170127235-170133891:-1;chr5:177819333-177825996:-1;chr5:178011598-178013284:1;chr5:178012552-178013725:1;chr5:179727970-179729762:1;chr5:180372516-180433497:-1;chr5:180513776-180521661:-1;chr5:22873048-22874638:1;chr5:23900133-23908133:-1;chr5:24367665-24376135:-1;chr5:256675-264719:-1;chr5:26794177-26804221:-1;chr5:36561793-36563258:1;chr5:42162740-42170255:-1;chr5:42625653-42633821:-1;chr5:45002546-45017293:-1;chr5:46267945-46278602:-1;chr5:49431762-49441278:1;chr5:57676700-57689379:-1;chr5:61572259-61579217:-1;chr5:682141-777717:1;chr5:6867784-6869779:1;chr5:694338-792942:-1;chr5:697000-792166:1;chr5:716867-805057:1;chr5:738955-837908:-1;chr5:743991-839621:1;chr5:744196-840886:-1;chr5:752387-849919:1;chr5:75464014-75470918:-1;chr5:81585-87897:-1;chr5:83945011-83958201:-1;chr5:87375106-87384636:-1;chr5:8748847-8750261:1;chr5:90497242-90505039:-1;chr5:98342206-98349944:-1;chr6:101492284-101499287:-1;chr6:102282866-102284419:1;chr6:103734294-103766182:-1;chr6:10465743-10533733:-1;chr6:112222297-112232034:-1;chr6:114016861-114018293:1;chr6:115109149-115110810:1;chr6:125706246-125714083:-1;chr6:133338939-133350611:-1;chr6:13879712-13886185:-1;chr6:153026910-153036437:-1;chr6:157730111-157736917:-1;chr6:161030179-161056645:-1;chr6:165722301-165734529:-1;chr6:167485153-167492491:-1;chr6:168714215-168721426:-1;chr6:169059363-169061018:1;chr6:170460937-170462140:1;chr6:170481359-170489342:-1;chr6:170498345-170499929:1;chr6:170530451-170531490:1;chr6:19762275-19773674:-1;chr6:24322889-24330506:-1;chr6:24808835-24820185:-1;chr6:29683283-29691176:-1;chr6:29841086-29851888:-1;chr6:29896583-29904063:-1;chr6:31205569-31214537:-1;chr6:31210168-31216078:-1;chr6:31226691-31317774:-1;chr6:31232348-31323961:-1;chr6:31237149-31328689:-1;chr6:31289762-31296176:-1;chr6:31374779-31475385:-1;chr6:31418671-31426931:-1;chr6:32440698-32536185:-1;chr6:32445810-32540814:-1;chr6:32448388-32497598:-1;chr6:32451086-32543542:-1;chr6:32491576-32557873:-1;chr6:32517559-32550811:-1;chr6:32559259-32567120:-1;chr6:33023805-33029949:-1;chr6:35136508-35138278:1;chr6:39812216-39813884:1;chr6:44011316-44012826:1;chr6:5035009-5041923:-1;chr6:53924717-53937438:-1;chr6:53926798-53936725:-1;chr6:56755374-56763618:-1;chr6:57282189-57292080:-1;chr6:57294221-57303996:-1;chr6:57420165-57432093:-1;chr6:57580284-57592561:-1;chr6:57620353-57630436:-1;chr6:58772845-58780119:-1;chr6:58775704-58777587:1;chr6:58776526-58777628:1;chr6:58776594-58777661:1;chr6:58776774-58777886:1;chr6:58776826-58777869:1;chr6:58776870-58777881:1;chr6:58776907-58778154:1;chr6:58777094-58778157:1;chr6:58777142-58778129:1;chr6:58777304-58777960:1;chr6:58777358-58778449:1;chr6:58777442-58778409:1;chr6:58777572-58778744:1;chr6:58777669-58778778:1;chr6:58777787-58778866:1;chr6:58777812-58778967:1;chr6:58777940-58779038:1;chr6:58778034-58779175:1;chr6:58778119-58779027:1;chr6:58778133-58779255:1;chr6:58778201-58779253:1;chr6:58778290-58779325:1;chr6:58778366-58779244:1;chr6:58778446-58779259:1;chr6:58778507-58779251:1;chr6:58778553-58779240:1;chr6:58778664-58779245:1;chr6:58778731-58779803:1;chr6:58778792-58779110:1;chr6:58778845-58779906:1;chr6:58778938-58779264:1;chr6:58779022-58779798:1;chr6:58779131-58779263:1;chr6:65344381-65352028:-1;chr6:66256836-66265037:-1;chr6:663457-670639:-1;chr6:67038069-67046169:-1;chr6:69685951-69693931:-1;chr6:74862724-74871560:-1;chr6:77434816-77461539:-1;chr6:81623554-81633193:-1;chr6:833435-835335:1;chr6:85315405-85327116:-1;chr6:86706056-86716771:-1;chr6:92858154-92865117:-1;chr7:100550770-100551726:1;chr7:100552209-100608567:-1;chr7:100676136-100684539:1;chr7:100999148-101006092:-1;chr7:103848822-103920020:-1;chr7:107369893-107371338:1;chr7:109433764-109456018:-1;chr7:110179280-110191243:-1;chr7:112434192-112478357:1;chr7:113413386-113424884:-1;chr7:126043230-126054095:-1;chr7:131706693-131707946:1;chr7:138334757-138336456:1;chr7:141753110-141786013:-1;chr7:141758220-141789641:1;chr7:142008263-142045683:-1;chr7:142098207-142137650:1;chr7:142098330-142173724:1;chr7:142357866-142364499:-1;chr7:142455117-142482328:1;chr7:142456708-142474565:-1;chr7:142458456-142486600:-1;chr7:142462103-142485408:1;chr7:142470164-142487802:-1;chr7:14510407-14511681:1;chr7:148028574-148029781:1;chr7:148070051-148078737:-1;chr7:150299344-150308456:-1;chr7:151986735-152075589:-1;chr7:152091393-152100120:-1;chr7:152278865-152286987:-1;chr7:154151617-154157990:-1;chr7:154389373-154402328:-1;chr7:155583942-155585371:1;chr7:157648599-157653870:-1;chr7:157877904-157884206:-1;chr7:158120622-158133298:-1;chr7:158498332-158507441:-1;chr7:20745870-20756109:-1;chr7:222245-228284:-1;chr7:24034673-24040609:-1;chr7:25054568-25062594:-1;chr7:27803942-27805459:1;chr7:29685730-29692837:-1;chr7:31312956-31321008:-1;chr7:32387376-32396008:-1;chr7:32772436-32779923:-1;chr7:37669870-37682984:-1;chr7:38383588-38400125:-1;chr7:49717457-49728482:-1;chr7:55283865-55291896:-1;chr7:56649663-56661616:-1;chr7:56759381-56772619:-1;chr7:57546698-57559197:-1;chr7:57955197-57961342:-1;chr7:61511323-61528790:-1;chr7:61738197-61785285:-1;chr7:61740507-61802344:1;chr7:61743574-61785282:-1;chr7:61780057-61800968:1;chr7:61785027-61796295:-1;chr7:61967155-61968196:1;chr7:61967160-61980780:1;chr7:61967161-61990912:1;chr7:61967170-61979333:-1;chr7:61967430-61969051:1;chr7:61968205-61969826:1;chr7:61968779-61969831:1;chr7:61968898-61969519:1;chr7:61968920-61969826:1;chr7:61969003-61969528:1;chr7:61969215-61969984:1;chr7:61969235-61970361:1;chr7:61969301-61970375:1;chr7:61969418-61970443:1;chr7:61969481-61970443:1;chr7:62001299-62007504:-1;chr7:628129-629369:1;chr7:64312575-64321009:-1;chr7:71209043-71215945:-1;chr7:73826104-73834116:-1;chr7:89517140-89532960:-1;chr7:89807908-89814481:-1;chr7:93414259-93426139:-1;chr7:9631769-9638761:-1;chr7:96473028-96484611:-1;chr7:96540975-96549939:-1;chr8:101437985-101439543:1;chr8:103992356-103999462:-1;chr8:1113157-1114992:1;chr8:112291251-112300281:-1;chr8:117761331-117763098:1;chr8:1182735-1192608:-1;chr8:11989773-12000340:-1;chr8:121869836-121877152:-1;chr8:126592330-126604249:-1;chr8:127189900-127197892:-1;chr8:128532913-128534743:1;chr8:129461651-129474101:-1;chr8:13151090-13152316:1;chr8:131909144-131910887:1;chr8:132275114-132283205:-1;chr8:133919775-133921589:1;chr8:135079902-135091941:-1;chr8:138123548-138129859:-1;chr8:138740335-138746938:-1;chr8:140972175-140973694:1;chr8:142836612-142838487:1;chr8:142955462-142956707:1;chr8:143266482-143267636:1;chr8:143512692-143514438:1;chr8:144324670-144326156:1;chr8:144492600-144493812:1;chr8:145180742-145181812:1;chr8:17962172-17970942:-1;chr8:18450927-18458728:-1;chr8:21374026-21375394:1;chr8:24969866-24993657:-1;chr8:25063760-25073325:-1;chr8:30596566-30598390:1;chr8:32677259-32694068:-1;chr8:40677546-40679031:1;chr8:40771549-40782509:-1;chr8:4120189-4127421:-1;chr8:42187596-42197541:-1;chr8:42736092-42742099:1;chr8:43092868-43097480:1;chr8:43510748-43514593:1;chr8:43822419-43831819:-1;chr8:46840696-46856107:1;chr8:47402881-47410642:-1;chr8:58116525-58125983:1;chr8:58122246-58123455:1;chr8:592089-602529:-1;ch hs1:120551483-120579772,hs1:145240050-145269993;hs1:248591351-248611374,hs1:248805350-248829601;hs1:120540786-120553823,hs1:145268492-145277906;hs1:120530492-120542696,hs1:145280819-145289948;hs1:120579029-120588901,hs1:145230350-145243341;hs1:16916601-16927382,hs1:21787218-21796973;hs1:16924563-16939088,hs1:21770053-21783099;hs1:17051781-17054491,hs1:234912242-234915037;hs1:17104247-17125579,hs1:234915659-234937807;hs1:149294684-149317646,hs1:149680279-149703828;hs1:120532755-120533301,hs1:145290148-145290930;hs1:120611243-120636529,hs1:145180665-145209916;hs1:120637472-120648611,hs1:145171283-145183076;hs1:149291154-149294376,hs1:149674168-149680261;hs1:120600581-120613679,hs1:145209791-145218760;hs1:248621000-248622647,hs1:248792838-248800230;hs1:120590343-120593985,hs1:145230430-145233047;hs1:120593825-120599214,hs1:145220123-145225244;hs1:149282663-149289493,hs1:149670767-149676317;hs1:196760142-196788265,hs1:196883898-196909895;hs1:196754804-196758588,hs1:196881743-196885706;hs1:149265409-149285916,hs1:149650199-149669569;hs1:121351932-121359452,hs1:121471830-121485306;hs1:120677059-120697000,hs1:145115310-145139358;hs1:144570577-144598745,hs1:148531360-148559762;hs1:16852191-16864727,hs1:17197481-17209452;hs1:196790245-196794779,hs1:196912152-196918389;hs1:144685808-144693422,hs1:144961064-144971385;hs1:144704208-144709945,hs1:144982701-144987948;hs1:144881075-144899881,hs1:146495803-146509799;hs1:144673460-144685733,hs1:144946497-144960570;hs1:120671755-120679309,hs1:145140064-145148587;hs1:142660400-142675550,hs1:143416700-143428903;hs1:17100517-17106945,hs1:234940556-234946727;hs1:149327422-149336207,hs1:149712016-149719920;hs1:149333558-149349722,hs1:149721455-149737171;hs1:142535769-142555335,hs1:143530140-143544448;hs1:17091843-17099130,hs1:234943599-234949947;hs1:120747216-120752625,hs1:143999046-144007997;hs1:16834371-16839926,hs1:17221122-17228873;hs1:144016380-144023939,hs1:206482222-206487680;hs1:144562714-144572639,hs1:148521489-148531354;hs1:142654101-142654971,hs1:143440582-143441374;hs1:144550328-144556356,hs1:148511538-148513936;hs1:144908784-144916419,hs1:146516113-146527190;hs1:16885697-16887707,hs1:17175820-17177273;hs1:16869683-16879882,hs1:17180704-17189601;hs1:144526689-144531188,hs1:149200583-149206169;hs1:144529343-144536341,hs1:149194636-149196611;hs1:144849247-144858627,hs1:146487297-146496576;hs1:144836662-144850392,hs1:146471886-146485391;hs1:17229235-17234397,hs1:149213023-149217948;hs1:17210026-17217121,hs1:149232360-149239156;hs1:17217509-17228485,hs1:149220599-149226923;hs1:142648178-142668746,hs1:143146768-143164786;hs1:149360722-149363448,hs1:149743372-149749596;hs1:144859498-144876117,hs1:149040079-149051131;hs1:47392196-47402907,hs1:47607126-47619404;hs1:47405616-47408448,hs1:47599659-47607196;hs1:121114036-121125732,hs1:206563089-206578109;hs1:142572072-142575529,hs1:143509991-143517290;hs1:142576995-142589805,hs1:143495004-143508563;hs1:142594356-142598477,hs1:143486520-143494556;hs1:142630461-142642819,hs1:143131818-143140524;hs1:144850082-144860008,hs1:149059651-149067732;hs1:89510563-89523894,hs1:89885160-89899184;hs1:16969780-16981319,hs1:17080743-17088478;hs1:47320546-47334452,hs1:47564304-47579285;hs1:207817305-207831742,hs1:207927054-207933176;hs1:144051990-144063424,hs1:206512276-206527592;hs1:143152234-143168375,hs1:143421450-143433028;hs1:16916629-16922419,hs1:145290205-145295376;hs1:822536-825932,hs1:5726032-5729144;hs1:91852781-91853075,hs1:145277428-145277445;hs1:144831486-144843590,hs1:145373273-145383773;hs1:145373548-145381574,hs1:146471607-146479355;hs1:721943-730429,hs1:224200464-224209288;hs1:12905130-12908841,hs1:13179787-13182246;hs1:145828924-145833014,hs1:147392110-147396338;hs1:142788544-142798535,hs1:143240377-143248099;hs1:142576787-142587439,hs1:142924944-142931945;hs1:120628471-120630136,hs1:145077436-145079971;hs1:157343796-157350605,hs1:157454568-157461228;hs1:16924049-16933424,hs1:149118879-149128522;hs1:120385455-120393239,hs1:145289198-145292793;hs1:91852770-91852936,hs1:108113427-108113548;hs1:16943273-16950610,hs1:17272720-17279528;hs1:248634104-248637577,hs1:248736354-248743194;hs1:39982999-39989752,hs1:40226079-40236083;hs1:142860825-142871476,hs1:143136861-143144872;hs1:16869700-16870669,hs1:17053150-17054081;hs1:16811347-16814769,hs1:16956146-16964294;hs1:148681616-148683927,hs1:148846082-148848262;hs1:207678388-207682539,hs1:207847418-207854782;hs1:16926154-16934152,hs1:120399570-120404740;hs1:17051977-17059920,hs1:17188342-17198187;hs1:142915787-142919828,hs1:143494985-143498965;hs1:73267282-73289681,hs1:121484328-121485353;hs1:16885874-16891323,hs1:21744339-21751235;hs1:17005018-17006286,hs1:234912719-234914169;hs1:25615412-25618334,hs1:25725184-25733761;hs1:16885860-16888559,hs1:149082586-149085439;hs1:24286307-24292417,hs1:118317701-118323993;hs1:168186211-168186443,hs1:182273404-182276785;hs1:222639560-222645161,hs1:224135755-224137192;hs1:49680923-49692464,hs1:121485036-121485259;hs1:79138475-79154758,hs1:121484314-121485351;hs1:85980257-85982386,hs1:146485542-146487311;hs1:145288996-145291435,hs1:149107890-149111783;hs1:73078177-73082895,hs1:121484730-121485336;hs1:104454701-104460630,hs1:121484578-121485329;hs1:121484143-121485162,hs1:191927703-191931090;hs1:170520838-170520838,hs1:209034275-209034283;hs1:121478647-121485396,hs10:42380251-42409675;hs1:121483957-121485356,hs10:42370585-42379885;hs1:121480914-121485397,hs10:42525867-42544645;hs1:121481183-121485293,hs10:42360733-42368869;hs1:121478656-121485380,hs10:42596723-42601910;hs1:242470688-242489646,hs10:38561226-38581396;hs1:149032819-149035700,hs10:42383521-42396881;hs1:242499028-242509676,hs10:38540170-38547103;hs1:242506954-242518523,hs10:38532036-38539213;hs1:242518114-242524267,hs10:38526958-38529648;hs1:242451023-242461457,hs10:38592109-38598367;hs1:242421164-242435340,hs10:38618530-38628972;hs1:242432981-242447946,hs10:38600162-38615261;hs1:121484424-121485385,hs10:42817309-42818086;hs1:121484634-121485199,hs10:42792551-42804402;hs1:162687502-162692455,hs10:65432629-65434136;hs1:149029240-149035699,hs10:42596804-42604642;hs1:121484213-121485272,hs10:38869123-38882294;hs1:162752679-162759475,hs10:38637988-38643163;hs1:50761497-50764375,hs10:57521176-57523637;hs1:121484613-121485384,hs10:42661695-42667226;hs1:224200464-224204167,hs10:127574500-127575769;hs1:142535477-142540108,hs10:42360178-42369213;hs1:149033989-149035764,hs10:42664480-42666908;hs1:121484518-121485385,hs10:34435622-34450432;hs1:121351657-121359702,hs11:51567272-51585340;hs1:121474693-121485369,hs11:51567293-51582966;hs1:121478651-121485386,hs11:48847290-48868556;hs1:108113076-108113516,hs11:85195020-85195169;hs1:121484451-121485385,hs11:50669984-50689852;hs1:121483244-121485382,hs11:48882630-48899206;hs1:121484986-121485390,hs11:50647417-50649495;hs1:231007769-231007799,hs11:12741498-12741501;hs1:121484152-121485384,hs11:55012403-55028498;hs1:121484326-121485370,hs11:12741489-12741501;hs1:121484729-121485351,hs11:50730532-50751148;hs1:121484390-121485152,hs11:100036107-100050978;hs1:121485131-121485375,hs11:82062436-82069054;hs1:121483246-121485379,hs12:34831473-34856392;hs1:121484827-121485377,hs12:74623793-74634451;hs1:108113077-108113508,hs12:127650471-127650898;hs1:121483248-121485390,hs12:58747398-58757774;hs1:197628714-197628718,hs12:95845351-95845351;hs1:9118402-9124249,hs14:93712706-93713121;hs1:160721594-160721603,hs14:87520597-87520600;hs1:121484316-121485387,hs14:85164663-85176483;hs1:121484658-121485293,hs14:47051158-47070926;hs1:121484818-121485378,hs14:42030963-42041001;hs1:121484581-121485372,hs15:20014740-20015591;hs1:8675287-8686714,hs15:22569253-22577401;hs1:121478654-121485397,hs16:46385808-46409667;hs1:121483329-121485293,hs16:46410074-46419837;hs1:121483541-121485358,hs16:46420042-46429519;hs1:5732941-5736079,hs16:33921683-33924957;hs1:121481168-121485375,hs16:46431427-46435511;hs1:149030860-149035631,hs16:46390795-46410110;hs1:149031319-149035728,hs16:46433662-46448367;hs1:142535711-142544125,hs16:33898828-33902269;hs1:142535516-142542613,hs16:33865059-33867798;hs1:121481947-121485384,hs16:34183153-34197506;hs1:121484648-121485166,hs16:33951061-33964080;hs1:121484797-121485274,hs16:56065452-56073776;hs1:121484423-121485349,hs16:34683885-34693912;hs1:121484524-121485239,hs16:33542081-33548860;hs1:121351620-121360791,hs17:22244732-22261803;hs1:142535915-142542688,hs17:25263173-25269799;hs1:121478653-121485295,hs17:22249730-22261591;hs1:91852790-91852965,hs17:55868701-55868709;hs1:176427632-176427632,hs17:17833222-17833226;hs1:121478642-121485379,hs18:18511175-18520291;hs1:121482743-121485388,hs18:107630-111716;hs1:121436614-121436616,hs18:18517162-18519925;hs1:121352990-121358996,hs18:18511528-18519282;hs1:121484605-121485178,hs18:25263684-25271120;hs1:192174578-192175901,hs18:108268-108634;hs1:121478628-121485398,hs19:27731776-27740548;hs1:91852769-91853096,hs19:36066493-36066715;hs1:91852772-91853053,hs19:24183646-24184778;hs1:121484484-121485196,hs19:27884498-27897684;hs1:121484504-121485202,hs19:27818069-27827691;hs1:121484498-121485293,hs19:21057255-21063911;hs1:144532018-144559138,hs2:5764105-5787196;hs1:144561522-144563675,hs2:5790167-5796942;hs1:117130944-117155893,hs2:91930324-91958376;hs1:117151194-117159473,hs2:91924330-91929982;hs1:117159475-117165083,hs2:91920951-91924935;hs1:91852777-91853098,hs2:133034402-133039173;hs1:148934737-148954413,hs2:91819075-91839535;hs1:148930035-148937866,hs2:91840571-91844857;hs1:121481179-121485378,hs2:92315392-92326127;hs1:121478658-121485385,hs2:92300683-92309716;hs1:121481179-121485375,hs2:92290241-92296872;hs1:148901195-148928173,hs2:91850371-91875367;hs1:121481181-121485379,hs2:92280859-92289233;hs1:91852773-91853000,hs2:230045483-230045639;hs1:148859554-148874454,hs2:91901637-91918967;hs1:121483937-121485369,hs2:133012318-133039293;hs1:121481183-121485389,hs2:89861301-89879888;hs1:121484467-121485329,hs2:92267675-92269692;hs1:143278517-143283775,hs2:162135490-162138701;hs1:143277520-143283746,hs2:133039388-133045646;hs1:121484692-121485356,hs2:89831734-89839728;hs1:142535864-142544579,hs2:89865176-89879563;hs1:149033347-149035715,hs2:89831802-89848695;hs1:33475522-33480144,hs2:32046989-32050569;hs1:149030150-149035699,hs2:92266980-92269717;hs1:247021010-247025407,hs2:162357494-162362734;hs1:12173727-12173795,hs2:133026713-133030933;hs1:104369924-104369928,hs2:133025353-133029793;hs1:4604624-4604787,hs2:133025147-133030650;hs1:48900032-48903446,hs2:202340549-202348190;hs1:121484672-121485360,hs2:58994656-59008990;hs1:121484215-121485296,hs2:155682852-155697119;hs1:121484599-121485166,hs2:232664465-232672130;hs1:230015025-230015025,hs2:101793486-101793490;hs1:121484505-121485385,hs20:26290440-26319469;hs1:143490221-143518632,hs21:9992953-10019843;hs1:143517747-143529107,hs21:10019818-10029865;hs1:143526585-143536370,hs21:10028800-10034763;hs1:143480750-143490151,hs21:9980190-9991059;hs1:143450705-143472380,hs21:9950035-9974817;hs1:143475183-143481254,hs21:9976945-9983717;hs1:143441369-143450289,hs21:9944148-9954025;hs1:142574984-142599304,hs21:9990264-10012986;hs1:142535710-142542692,hs21:10780105-10809944;hs1:142535522-142546631,hs21:10084965-10089783;hs1:143275169-143284796,hs21:9694887-9705486;hs1:142908961-142918870,hs21:10134858-10143096;hs1:142896533-142907550,hs21:10147639-10156125;hs1:142614912-142624890,hs21:9645611-9654065;hs1:121484527-121485386,hs21:10746671-10759086;hs1:121483247-121485375,hs21:10730509-10736536;hs1:142645803-142654581,hs21:9938767-9947113;hs1:224198575-224204156,hs21:10823881-10849746;hs1:121484124-121485385,hs21:10780498-10807668;hs1:143536212-143544459,hs21:10085446-10092811;hs1:142964629-142967277,hs21:10084960-10087786;hs1:142585474-142593802,hs21:10127842-10139885;hs1:143487724-143498834,hs21:10134860-10141424;hs1:121484792-121485369,hs21:11120286-11137741;hs1:121484434-121485356,hs21:11171964-11186876;hs1:148846556-148850172,hs21:9440272-9447330;hs1:160721590-160721603,hs21:10780115-10796085;hs1:121483241-121485384,hs22:16849194-16861888;hs1:149031633-149035684,hs22:16850188-16861803;hs1:109647790-109653396,hs22:30163398-30165865;hs1:143527551-143544358,hs3:75902207-75914828;hs1:142608871-142626480,hs3:75822755-75843962;hs1:142601802-142605217,hs3:75846899-75849500;hs1:121483258-121485364,hs3:90485974-90499538;hs1:121484516-121485385,hs3:90473400-90479724;hs1:16963586-16978955,hs3:49721787-49733481;hs1:142640049-142646216,hs3:75810603-75816912;hs1:142653563-142658776,hs3:75798165-75805501;hs1:143503186-143513591,hs3:75872977-75878566;hs1:143493701-143501860,hs3:75860649-75867976;hs1:121484595-121485307,hs3:90451571-90466971;hs1:142542334-142558464,hs3:75902225-75914601;hs1:121484120-121485367,hs3:196625648-196625726;hs1:121484443-121485294,hs3:79633664-79647168;hs1:121484757-121485297,hs3:167430984-167439043;hs1:121484674-121485307,hs3:176737068-176745242;hs1:16978136-16979697,hs3:18947221-18949184;hs1:225062248-225062252,hs3:122461798-122461798;hs1:91852773-91853102,hs4:70296655-70296715;hs1:121484126-121485386,hs4:68264294-68266758;hs1:143278370-143283788,hs4:49511204-49520214;hs1:143278775-143283775,hs4:49300514-49316521;hs1:143277651-143283750,hs4:49320845-49326213;hs1:143278762-143284707,hs4:49290606-49296475;hs1:142616651-142627215,hs4:49162012-49171446;hs1:243324554-243331946,hs4:119431418-119438517;hs1:142535968-142542959,hs4:49633431-49648595;hs1:143174133-143180574,hs4:49567322-49577593;hs1:121484143-121485363,hs4:49634622-49659558;hs1:143118588-143125056,hs4:49162359-49171735;hs1:243355930-243361911,hs4:119400895-119406098;hs1:121484487-121485367,hs4:49143768-49158975;hs1:143161608-143175549,hs4:49211486-49223894;hs1:243270139-243274842,hs4:119488863-119496997;hs1:142535518-142542930,hs4:49104357-49115564;hs1:50759106-50761362,hs4:102287805-102290215;hs1:121484144-121485387,hs4:49117346-49125950;hs1:243130185-243137022,hs4:119380319-119387792;hs1:224199397-224204158,hs4:49149780-49157356;hs1:148945227-148951798,hs4:9775226-9782239;hs1:121484615-121484797,hs4:97329007-97329826;hs1:121484527-121485385,hs4:52681161-52695627;hs1:121481186-121485364,hs4:81196719-81203444;hs1:121484952-121485185,hs4:42604357-42609450;hs1:121485061-121485387,hs5:46333630-46340277;hs1:121484430-121485382,hs5:46392840-46399696;hs1:121484331-121485356,hs5:46370965-46382362;hs1:121290429-121310066,hs5:49698339-49713712;hs1:121209491-121217495,hs5:49770750-49776227;hs1:121171600-121176485,hs5:49817394-49822785;hs1:91852784-91853070,hs5:71146738-71146889;hs1:108904373-108915143,hs5:85565566-85577186;hs1:108756961-108766287,hs5:85594184-85603641;hs1:121352241-121355744,hs5:46380256-46380875;hs1:91852783-91853046,hs5:128583214-128583218;hs1:121484580-121485329,hs5:72128519-72134343;hs1:121478650-121485388,hs6:58773645-58780119;hs1:91852771-91853053,hs6:119558562-119558673;hs1:121484391-121485387,hs6:61911418-61914294;hs1:219761233-219766044,hs6:66030724-66036341;hs1:91852795-91853049,hs6:133593999-133594080;hs1:89173018-89182538,hs6:58778158-58778675;hs1:237715925-237725923,hs6:58776810-58778138;hs1:24600293-24600298,hs6:71705812-71706525;hs1:121478653-121485388,hs7:61967155-61987495;hs1:121484224-121485358,hs7:61990609-61998539;hs1:83808365-83815586,hs7:76433681-76444083;hs1:83823055-83831176,hs7:76441328-76451758;hs1:83837691-83849623,hs7:76456898-76468829;hs1:83884526-83895325,hs7:76502869-76518179;hs1:83800722-83803796,hs7:76427242-76434629;hs1:83899371-83913768,hs7:76516498-76531592;hs1:83918361-83923007,hs7:76535598-76541340;hs1:121481186-121485384,hs7:61079181-61096857;hs1:121352044-121358178,hs7:61984918-61996317;hs1:83676780-83686399,hs7:76307535-76316527;hs1:142535462-142545028,hs7:57546089-57556769;hs1:121484140-121485358,hs7:61780834-61803063;hs1:121484570-121485331,hs7:61211520-61216673;hs1:149029430-149035413,hs7:61055182-61061766;hs1:83636022-83647134,hs7:76182633-76191448;hs1:121484286-121485387,hs7:107410604-107410635;hs1:121484182-121485387,hs7:61742974-61758255;hs1:121484116-121485350,hs7:57546757-57556750;hs1:149033045-149035679,hs7:61784711-61801165;hs1:83757941-83764201,hs7:76384748-76392511;hs1:160721587-160721601,hs7:17864884-17864886;hs1:121484464-121485370,hs7:17862752-17866589;hs1:121484656-121485338,hs7:143845803-143857207;hs1:121484726-121485201,hs7:115445211-115448884;hs1:121485144-121485364,hs7:65058620-65061265;hs1:121478654-121485367,hs8:43090307-43097469;hs1:764872-781085,hs8:264560-278300;hs1:781297-790092,hs8:256454-261006;hs1:790457-799776,hs8:240677-252117;hs1:121484319-121485379,hs8:43792444-43799157;hs1:121483253-121485344,hs8:43785640-43786746;hs1:121481187-121485360,hs8:46846156-46861502;hs1:121484613-121485295,hs8:43822420-43838671;hs1:145277428-145277444,hs8:70602348-70602565;hs1:91852790-91853015,hs8:82754661-82754754;hs1:24994163-24999638,hs8:128097683-128103064;hs1:248601574-248601577,hs8:73355277-73355277;hs1:121483473-121485372,hs9:66820977-66824577;hs1:121484653-121485352,hs9:66833829-66843906;hs1:121484421-121485383,hs9:68995978-69006085;hs1:142831883-142832823,hs9:44069551-44070743;hs1:121484721-121485355,hs9:101671648-101680199;hs1:121484525-121485341,hsX:61814922-61818428;hs1:121478651-121485311,hsX:61835341-61839297;hs1:121474104-121485347,hsX:58554693-58563838;hs1:121484116-121485363,hsX:61725143-61735054;hs1:121351841-121356782,hsX:61710577-61725733;hs1:121481182-121485366,hsX:61751809-61768611;hs1:121351971-121356763,hsX:58560256-58565613;hs1:121352246-121356768,hsX:61815630-61823540;hs1:145277428-145277444,hsX:108297377-108297727;hs1:121484673-121485262,hsX:144227578-144230519;hs1:5714016-5719833,hsY:9975587-9984742;hs1:5725950-5736057,hsY:9979890-9995743;hs1:815015-826121,hsY:9966495-9986123;hs1:143525056-143544456,hsY:13425832-13448774;hs1:121478657-121485385,hsY:13460747-13489227;hs1:142535505-142559637,hsY:13430855-13459300;hs1:142570253-142598630,hsY:13393204-13419935;hs1:143510850-143518625,hsY:13410772-13421152;hs1:143495004-143509972,hsY:13398509-13413208;hs1:121484497-121485353,hsY:13450017-13459312;hs1:143486315-143494154,hsY:13391834-13397946;hs1:121481948-121485384,hsY:58974830-58997434;hs1:142535474-142542672,hsY:58972749-58983548;hs1:243071457-243088158,hsY:13930213-13945857;hs1:142607972-142618888,hsY:13372665-13380010;hs1:143454882-143467282,hsY:13356884-13368608;hs1:143443809-143453650,hsY:13348275-13354804;hs1:143240870-143245554,hsY:13285715-13295123;hs1:243049026-243055978,hsY:13907742-13911246;hs1:143260498-143266670,hsY:13269576-13275383;hs1:121484583-121485361,hsY:13841188-13851948;hs1:142535766-142539480,hsY:28798249-28802785;hs1:142535869-142542689,hsY:28784420-28793638;hs1:142785373-142792949,hsY:13283053-13293083;hs1:121484443-121485367,hsY:13808324-13826110;hs1:142918405-142926854,hsY:13400508-13409077;hs1:142535592-142542688,hsY:13136625-13143384;hs1:242205472-242207955,hsY:9951444-9957244;hs1:242964907-242971522,hsY:13878904-13888110;hs1:202426301-202433567,hsY:28462140-28468830;hs1:227758084-227760149,hsY:9991607-9996465;hs1:224200252-224203274,hsY:13809973-13817789;hs1:148859558-148862944,hsY:59005627-59014482;hs2:133038761-133047122,hs2:162135071-162138982;hs2:92302571-92309710,hs2:132996190-133003831;hs2:92280859-92297448,hs2:132994957-133004826;hs2:149688586-149690546,hs2:149790575-149792393;hs2:92272935-92276691,hs2:132996322-133006442;hs2:92315392-92319755,hs2:132996463-133004811;hs2:92320103-92324830,hs2:132995040-133001500;hs2:89070552-89082641,hs2:96593648-96608551;hs2:62955352-62960725,hs2:133020843-133030591;hs2:96609728-96619821,hs2:97811816-97827270;hs2:96598256-96606060,hs2:97825950-97838144;hs2:90467453-90477799,hs2:91684785-91696553;hs2:90450641-90463954,hs2:91670019-91684800;hs2:110107516-110109253,hs2:110251348-110252768;hs2:130976218-130987160,hs2:132202147-132213420;hs2:89069698-89081649,hs2:97828855-97840208;hs2:87061333-87077585,hs2:107115607-107133938;hs2:87084137-87088327,hs2:107101420-107106833;hs2:89833919-89851850,hs2:92267780-92272459;hs2:87816446-87833661,hs2:112172811-112192220;hs2:87102009-87110648,hs2:112626077-112637065;hs2:130988823-130998268,hs2:132188648-132201362;hs2:2299310-2299519,hs2:133021768-133031254;hs2:87760963-87769655,hs2:112240035-112249641;hs2:87741389-87749204,hs2:112259410-112263919;hs2:87507293-87528996,hs2:112314499-112339446;hs2:87473525-87482416,hs2:112362634-112374477;hs2:131033521-131042656,hs2:132125296-132133479;hs2:130894969-130901719,hs2:132287468-132294738;hs2:89101128-89106081,hs2:96515924-96523162;hs2:87430319-87436270,hs2:112513338-112518142;hs2:87453842-87456098,hs2:112491702-112498505;hs2:133024057-133029789,hs2:155511469-155511526;hs2:106855189-106865974,hs2:108525724-108531452;hs2:96405734-96409794,hs2:114138334-114143848;hs2:87969275-87975222,hs2:112031007-112036221;hs2:87934115-87941004,hs2:112064130-112071292;hs2:87927647-87931060,hs2:112076277-112079221;hs2:106894135-106902291,hs2:110434169-110438406;hs2:86956120-86962188,hs2:87287654-87297851;hs2:96321587-96332380,hs2:114056882-114067096;hs2:1217119-1218475,hs2:133022653-133030580;hs2:90416499-90424253,hs2:91638462-91645388;hs2:87567624-87571503,hs2:91756805-91761492;hs2:89077374-89083531,hs2:98175831-98181972;hs2:65832132-65832148,hs2:133022648-133030551;hs2:96733266-96736089,hs2:98242400-98244745;hs2:49498852-49498860,hs2:133025668-133030980;hs2:51581400-51581421,hs2:133021757-133029781;hs2:37156987-37157166,hs2:91692829-91694038;hs2:123358248-123358254,hs2:133026229-133030999;hs2:89851165-89856495,hs20:29810820-29828977;hs2:89864993-89878471,hs20:29810431-29825657;hs2:89868567-89878929,hs20:29827979-29832833;hs2:92304548-92309683,hs20:26310760-26319416;hs2:92316283-92324816,hs20:26301433-26319420;hs2:89865480-89879391,hs20:29803976-29806096;hs2:92272965-92282186,hs20:26306564-26319419;hs2:132995521-133004821,hs20:26306926-26317360;hs2:133022658-133029058,hs20:60924739-60924760;hs2:133012616-133013138,hs20:26188811-26189350;hs2:162135135-162139146,hs21:9828071-9832719;hs2:133010902-133016033,hs21:9825438-9827473;hs2:89850686-89879081,hs21:10796346-10819819;hs2:89858987-89879074,hs21:10830329-10839155;hs2:89862455-89879884,hs21:10783299-10801080;hs2:95538875-95559512,hs21:9890637-9910930;hs2:162135072-162138954,hs21:9692904-9700274;hs2:95523504-95528461,hs21:9919128-9928303;hs2:91894437-91906737,hs21:11018958-11033521;hs2:133040803-133048748,hs21:9827219-9834058;hs2:132658285-132670106,hs21:14618976-14631928;hs2:132540072-132546242,hs21:9842949-9851062;hs2:133034588-133039078,hs21:15457341-15457388;hs2:133040238-133048998,hs21:9696095-9702554;hs2:133021979-133031218,hs21:47400474-47404587;hs2:132662163-132672750,hs21:29310557-29319940;hs2:92191993-92194771,hs21:9564222-9568642;hs2:89103779-89105569,hs21:11020311-11022262;hs2:230045549-230045707,hs21:15457341-15457389;hs2:96515697-96517870,hs21:11020320-11022767;hs2:89830439-89849735,hs22:16848485-16863116;hs2:92267616-92272476,hs22:16848481-16862360;hs2:91954237-91960011,hs22:24998859-25002665;hs2:114394990-114404882,hs22:51204705-51214271;hs2:114385696-114392447,hs22:51214764-51219996;hs2:92054682-92057906,hs22:16891121-16898941;hs2:133023318-133030945,hs22:25489773-25489792;hs2:133022668-133027480,hs22:46389189-46389191;hs2:133025812-133031235,hs3:107082625-107082658;hs2:85771612-85772068,hs3:112411935-112417646;hs2:189026506-189026506,hs3:194188359-194188364;hs2:133016595-133035486,hs4:80273528-80274719;hs2:89850901-89879899,hs4:49633677-49659926;hs2:91792955-91808799,hs4:4190365-4206892;hs2:91783210-91798246,hs4:4210216-4219776;hs2:91763739-91787039,hs4:4222537-4239994;hs2:91761065-91768099,hs4:4240495-4243501;hs2:91810025-91812305,hs4:4190037-4192269;hs2:91807691-91817544,hs4:4182994-4189648;hs2:89856653-89879886,hs4:49139434-49158573;hs2:89850863-89879900,hs4:49100182-49125926;hs2:89864483-89879567,hs4:49093896-49099715;hs2:162135065-162139131,hs4:49322932-49326755;hs2:162135210-162138962,hs4:49313330-49318664;hs2:162135080-162138951,hs4:49512300-49520441;hs2:133039606-133047181,hs4:49512318-49518977;hs2:133040238-133045660,hs4:49315068-49319507;hs2:133039801-133045659,hs4:49291293-49294161;hs2:162135494-162138932,hs4:49288017-49289452;hs2:133005901-133016375,hs4:190632392-190639048;hs2:91814407-91821749,hs4:9763699-9768721;hs2:42051474-42052445,hs4:66411166-66416169;hs2:230045484-230045591,hs4:76807176-76807202;hs2:133034734-133039027,hs4:76807178-76807201;hs2:133028362-133033356,hs4:8501330-8501343;hs2:92316765-92320137,hs4:68260433-68265993;hs2:133026137-133030462,hs4:120724149-120724154;hs2:23258719-23258719,hs4:112187988-112187993;hs2:133021088-133030981,hs5:32370428-32370444;hs2:68914248-68914601,hs5:64465125-64470112;hs2:133026715-133031901,hs5:1198614-1199752;hs2:183371061-183375268,hs5:85541213-85546910;hs2:92315395-92326127,hs6:58774963-58779317;hs2:92300658-92309711,hs6:58774497-58779192;hs2:133032888-133038161,hs6:119558563-119558676;hs2:92267783-92278383,hs6:58773629-58779248;hs2:133016789-133034036,hs6:58773858-58779070;hs2:89831857-89838280,hs6:58774667-58778708;hs2:89870376-89879948,hs6:58776723-58779190;hs2:142414181-142424851,hs6:58777125-58779827;hs2:89830496-89849857,hs7:61780638-61802870;hs2:89830800-89853206,hs7:61744220-61759059;hs2:92304047-92309692,hs7:61079044-61088413;hs2:92316221-92319101,hs7:61079034-61085267;hs2:92290375-92300695,hs7:61967415-61971201;hs2:92305739-92319752,hs7:61967576-61973577;hs2:92267422-92276684,hs7:61780462-61803746;hs2:92272816-92284094,hs7:61967408-61969520;hs2:92262971-92269692,hs7:61967572-61969517;hs2:92295914-92300679,hs7:61079044-61085212;hs2:92273037-92279846,hs7:61079169-61090147;hs2:133022383-133029643,hs7:61967419-61969673;hs2:89830775-89846728,hs7:57546322-57555691;hs2:92267778-92271415,hs7:61740983-61757175;hs2:89842322-89853218,hs7:61967420-61969682;hs2:89870069-89878619,hs7:61968973-61969456;hs2:92268091-92273545,hs7:57546370-57555690;hs2:84101463-84108533,hs7:153104892-153110471;hs2:133022657-133026775,hs7:50009416-50009427;hs2:21284888-21284898,hs7:17864884-17864886;hs2:191231124-191231146,hs7:17864879-17864886;hs2:232641311-232641314,hs7:133537771-133537771;hs2:92290373-92317760,hs8:43781082-43799155;hs2:92300690-92325762,hs8:46850600-46857412;hs2:92280958-92290929,hs8:46842067-46857411;hs2:92296735-92297296,hs8:46852452-46856788;hs2:92272969-92279919,hs8:46852446-46856788;hs2:133022658-133028529,hs8:143337507-143337523;hs2:243032077-243039102,hs8:357897-366787;hs2:243005681-243018089,hs8:335025-343735;hs2:92273177-92276692,hs8:43820865-43825831;hs2:92302573-92309261,hs8:43817940-43825822;hs2:92315392-92324441,hs8:43092787-43096437;hs2:92315976-92321303,hs8:46900391-46904682;hs2:133024098-133035828,hs8:82754626-82754756;hs2:133034613-133039083,hs8:70602351-70602565;hs2:133024169-133034277,hs8:13047297-13047308;hs2:92303975-92309784,hs9:66833131-66835749;hs2:92289725-92300707,hs9:66833084-66835888;hs2:92315396-92324218,hs9:66833104-66839668;hs2:92272649-92275216,hs9:66833134-66835045;hs2:92272957-92276690,hs9:66821693-66824583;hs2:92304826-92309698,hs9:66800759-66800784;hs2:92320117-92321753,hs9:66800760-66800785;hs2:92305663-92308043,hs9:67320779-67320858;hs2:92280547-92291135,hs9:67320697-67321782;hs2:132994957-133004829,hs9:66833081-66836350;hs2:133110117-133122822,hs9:66481854-66492323;hs2:95468971-95475137,hs9:44065710-44070741;hs2:133118467-133121149,hs9:68378628-68385387;hs2:116374384-116379152,hs9:131457077-131458542;hs2:114173233-114173996,hs9:70836735-70838003;hs2:133034448-133038908,hs9:79186759-79186889;hs2:133029238-133034731,hs9:1881749-1881751;hs2:89868567-89879345,hs9:72653115-72653308;hs2:230045516-230045591,hs9:79186644-79186853;hs2:133030457-133035832,hsX:136520392-136520543;hs2:133022267-133030588,hsX:1259691-1260951;hs2:133021901-133026942,hsX:20656815-20656832;hs2:133025608-133030922,hsX:583002-589451;hs2:133024098-133030936,hsX:25303681-25303693;hs2:213118185-213118185,hsX:95415801-95415803;hs2:98694232-98694236,hsX:89674838-89674838;hs2:133016892-133018893,hsX:79238790-79238792;hs2:133014866-133035827,hsY:10014535-10034957;hs2:133006374-133013582,hsY:10031706-10039752;hs2:133005466-133009488,hsY:10041430-10049961;hs2:89868170-89879889,hsY:13845604-13868022;hs2:89850406-89860601,hsY:13841177-13869984;hs2:89865417-89876799,hsY:13832250-13844036;hs2:89851845-89879856,hsY:13446564-13461090;hs2:89850150-89863488,hsY:13801096-13817788;hs2:95546218-95559989,hsY:13292527-13302848;hs2:91913159-91917764,hsY:59005248-59015134;hs2:95564495-95571830,hsY:13280610-13291016;hs2:89850687-89856543,hsY:13678526-13688803;hs2:92305728-92309223,hsY:13479625-13489121;hs2:89864629-89879820,hsY:58972564-58982051;hs2:62955044-62959966,hsY:10019105-10026957;hs2:95526396-95529038,hsY:13320164-13323076;hs2:89867302-89878357,hsY:13137787-13143827;hs2:89868091-89877657,hsY:58819692-58819713;hs2:89076334-89081799,hsY:58969805-58974016;hs2:2299337-2299509,hsY:10019104-10027352;hs2:49498851-49498860,hsY:10019086-10022521;hs2:97807816-97809229,hsY:58968293-58969708;hs2:96625171-96633115,hsY:58968048-58974540;hs3:195393885-195419809,hs3:195683001-195707160;hs3:63287-79399,hs3:75287476-75299751;hs3:60199-62992,hs3:75274586-75279081;hs3:10088028-10095904,hs3:11909371-11915340;hs3:10101963-10108991,hs3:11922942-11929237;hs3:75463585-75466665,hs3:129807139-129813591;hs3:75460660-75463354,hs3:129799540-129801908;hs3:195339584-195349601,hs3:195445107-195455809;hs3:123717514-123725025,hs3:125671177-125676636;hs3:123707934-123717071,hs3:125684894-125690866;hs3:75384184-75394987,hs3:123427715-123437677;hs3:10034185-10038489,hs3:11909717-11914997;hs3:87051-98389,hs3:75312829-75319492;hs3:195348062-195364062,hs3:197377330-197393263;hs3:195345834-195349785,hs3:195473361-195479353;hs3:162509932-162512072,hs3:162626721-162629501;hs3:75747835-75757430,hs3:197841096-197846217;hs3:195708940-195717679,hs3:197348902-197357799;hs3:10046206-10051283,hs3:11947592-11955846;hs3:123435576-123443476,hs3:125397889-125404008;hs3:100931943-100931949,hs3:149927901-149927901;hs3:75741994-75756685,hs4:190907116-190924176;hs3:75720002-75735255,hs4:190922505-190937403;hs3:75720704-75723996,hs4:190940652-190942111;hs3:75705901-75710920,hs4:190953226-190958757;hs3:75703275-75709137,hs4:190961345-190963490;hs3:75688834-75700296,hs4:190965133-190971825;hs3:75825245-75835626,hs4:49162031-49171403;hs3:197842873-197846294,hs4:190914293-190919426;hs3:197851198-197856545,hs4:190897435-190902288;hs3:129797454-129806820,hs4:9717675-9724254;hs3:51893678-51900829,hs4:110513988-110519777;hs3:195417672-195422277,hs5:264442-267979;hs3:75792753-75799184,hs5:27668025-27668100;hs3:90484756-90504055,hs6:58773633-58779263;hs3:90470704-90478907,hs6:58773755-58779234;hs3:90451542-90459050,hs6:58773877-58779216;hs3:46493639-46493644,hs6:162651285-162651285;hs3:13980817-13980820,hs6:96964073-96964073;hs3:90470478-90479304,hs7:61967576-61972920;hs3:90498371-90499585,hs7:61968965-61976575;hs3:197864874-197867003,hs7:79509-81504;hs3:94221703-94227225,hs7:102736016-102742284;hs3:183319125-183319125,hs7:82210010-82210013;hs3:111274093-111274944,hs8:128531802-128537061;hs3:155026190-155028847,hs8:101715491-101721757;hs3:75716102-75739578,hs9:68394565-68416820;hs3:75720015-75746777,hs9:66456489-66473844;hs3:75740270-75744830,hs9:68393468-68398209;hs3:197848622-197852906,hs9:141072630-141078120;hs3:75794224-75802831,hs9:66858962-66862724;hs3:75799019-75803222,hs9:68990025-69003446;hs3:11388018-11388018,hs9:93783183-93783186;hs3:75730413-75754857,hsY:9931335-9959760;hs3:75749914-75757188,hsY:9960154-9967554;hs3:75716069-75719119,hsY:13460861-13488411;hs3:75862150-75880544,hsY:13398825-13419227;hs3:197841104-197847630,hsY:9956418-9966539;hs3:75718061-75718729,hsY:58983726-58997073;hs3:75900520-75909692,hsY:13427903-13437969;hs3:75910725-75913772,hsY:13441946-13446649;hs4:49100557-49128807,hs4:49631274-49659847;hs4:49093942-49099633,hs4:49646641-49657341;hs4:49140054-49163005,hs4:49630001-49659824;hs4:49300688-49304039,hs4:49512304-49518929;hs4:49309206-49326212,hs4:49512332-49519070;hs4:16686-23035,hs4:191026661-191039368;hs4:27343-29761,hs4:191017833-191021618;hs4:49223145-49245617,hs4:49550646-49576019;hs4:49170339-49178473,hs4:49620557-49627951;hs4:49290115-49298557,hs4:49512297-49517549;hs4:144751804-144779778,hs4:144870278-144898508;hs4:49211857-49216872,hs4:49577595-49587538;hs4:144741340-144749506,hs4:144864974-144872648;hs4:144777019-144785797,hs4:144898983-144909051;hs4:69371345-69375071,hs4:69488579-69493072;hs4:69381684-69397520,hs4:69491111-69504753;hs4:144803447-144812922,hs4:144924360-144928474;hs4:144790921-144802499,hs4:144908984-144922472;hs4:144882368-144899793,hs4:144986776-145002768;hs4:70083409-70090811,hs4:70246806-70249328;hs4:69678827-69697788,hs4:69869989-69888888;hs4:120294048-120299685,hs4:166176511-166186480;hs4:69414831-69426843,hs4:69519687-69532331;hs4:49261867-49268288,hs4:49533721-49537814;hs4:120271029-120282442,hs4:166156969-166164988;hs4:144800570-144812958,hs4:145041846-145056119;hs4:144818626-144825922,hs4:145056407-145058395;hs4:70029739-70043789,hs4:70194519-70206686;hs4:144785329-144797978,hs4:145007174-145022194;hs4:120307859-120314172,hs4:166192594-166199997;hs4:144711042-144716874,hs4:144950447-144958498;hs4:144706144-144714080,hs4:144838828-144843673;hs4:70296648-70296715,hs4:76807174-76807201;hs4:70155174-70158831,hs4:70284563-70289815;hs4:63236-67922,hs4:49512708-49513975;hs4:75323505-75325627,hs4:75490460-75492722;hs4:105035759-105036566,hs4:105743903-105745247;hs4:190682235-190684017,hs5:154275169-154275238;hs4:76807181-76807198,hs5:71146737-71146750;hs4:68264290-68266436,hs6:58773639-58778903;hs4:49100557-49122286,hs6:58773642-58779042;hs4:49142548-49156224,hs6:58774109-58779222;hs4:94864218-94873455,hs6:58776502-58779100;hs4:94114789-94119230,hs6:58776499-58778528;hs4:68264288-68271232,hs7:61967361-61987007;hs4:33834881-33855121,hs7:57605756-57622932;hs4:111356824-111368452,hs7:62638341-62648207;hs4:49634890-49641169,hs7:61967415-61969506;hs4:49149355-49158984,hs7:57547588-57553532;hs4:120360430-120366209,hs7:45820654-45826537;hs4:109155769-109166869,hs7:61968934-61969512;hs4:70296662-70296713,hs8:70602321-70602468;hs4:190800875-190828436,hs9:68480302-68508984;hs4:190870577-190884786,hs9:68424030-68440486;hs4:190891506-190895911,hs9:68421465-68429263;hs4:190190833-190202871,hs9:68412874-68428448;hs4:190829952-190839153,hs9:68470928-68482644;hs4:190860182-190870192,hs9:68450038-68456894;hs4:190856036-190859682,hs9:68455160-68459011;hs4:190840009-190846756,hs9:68463463-68473217;hs4:190940986-190942585,hs9:68414319-68415891;hs4:190932861-190942319,hs9:68403776-68412973;hs4:190796419-190807443,hs9:69007303-69015412;hs4:190814457-190825854,hs9:68683410-68696781;hs4:190805551-190821639,hs9:69019039-69033952;hs4:190925766-190934775,hs9:66459192-66465155;hs4:190796410-190807166,hs9:68672646-68676973;hs4:190798563-190804153,hs9:68668276-68669528;hs4:3568014-3574025,hs9:44739376-44744627;hs4:190857055-190867471,hs9:69062980-69073299;hs4:132611165-132616648,hs9:67827178-67831583;hs4:190906410-190924600,hsY:9950786-9973294;hs4:49633430-49659842,hsY:13445917-13461213;hs4:80273499-80274702,hsY:10019110-10031762;hs4:49100616-49126734,hsY:13446562-13463243;hs4:49142556-49156931,hsY:13448665-13460755;hs4:49093823-49099699,hsY:13446562-13458359;hs4:49101026-49122972,hsY:13849162-13864158;hs4:49633987-49647026,hsY:13841388-13846460;hs4:49633411-49640083,hsY:13853117-13869971;hs4:49644504-49648712,hsY:13851980-13868003;hs4:49147595-49158516,hsY:13853090-13868006;hs4:49146831-49158335,hsY:13841074-13850535;hs4:49147932-49152922,hsY:13861209-13869807;hs4:49637566-49650694,hsY:13824324-13833851;hs4:49105009-49119925,hsY:13801134-13811009;hs4:49144117-49152529,hsY:13806550-13817781;hs4:49633656-49644930,hsY:58972279-58977111;hs4:49093355-49102398,hsY:58972575-58980693;hs4:49145686-49157990,hsY:58972291-58980754;hs4:49100557-49110236,hsY:28784271-28789480;hs4:190632457-190638750,hsY:10031993-10039198;hs4:49641002-49656863,hsY:13137786-13141786;hs5:20810928-20834650,hs5:34370107-34396105;hs5:175346214-175366399,hs5:177330004-177349961;hs5:20833855-20839396,hs5:34364706-34369646;hs5:20840088-20858506,hs5:34350108-34365265;hs5:175335216-175343451,hs5:177349560-177359405;hs5:20910397-20918616,hs5:34283144-34289604;hs5:20854826-20859886,hs5:34343513-34349779;hs5:20802466-20809955,hs5:34393450-34399767;hs5:20870001-20875006,hs5:34331560-34337713;hs5:20875514-20886341,hs5:34318795-34330762;hs5:20920097-20934285,hs5:34270017-34281889;hs5:20886524-20898629,hs5:34308751-34316266;hs5:20933584-20940161,hs5:34262225-34269016;hs5:22199876-22216825,hs5:70728735-70744671;hs5:98730654-98746275,hs5:99691170-99708640;hs5:177373202-177385478,hs5:178938647-178946903;hs5:175410445-175419790,hs5:177275049-177289553;hs5:22194263-22198710,hs5:70720857-70725496;hs5:98750688-98758770,hs5:99675447-99687796;hs5:286357-307135,hs5:1603154-1616141;hs5:175429789-175441582,hs5:177256390-177268617;hs5:175634008-175647952,hs5:177117316-177129251;hs5:22168172-22179790,hs5:70696561-70707692;hs5:20747163-20750606,hs5:34108170-34114837;hs5:21479540-21483663,hs5:34188330-34197924;hs5:20734645-20744297,hs5:34117370-34126101;hs5:98801868-98808649,hs5:99439967-99445694;hs5:98812386-98822522,hs5:99425851-99436253;hs5:37449089-37457175,hs5:98843103-98849154;hs5:17504318-17513089,hs5:17615063-17629644;hs5:175662648-175667327,hs5:177095098-177104824;hs5:175462808-175473893,hs5:177226770-177234413;hs5:21523304-21524287,hs5:29424519-29425647;hs5:113882481-113890411,hs5:117156294-117165243;hs5:20771657-20784561,hs5:34078239-34091302;hs5:175716094-175728805,hs5:177047229-177058806;hs5:170255559-170263314,hs5:178179732-178186958;hs5:263074-270262,hs5:1633244-1636235;hs5:98907550-98914624,hs5:99071411-99074621;hs5:16186438-16192471,hs5:16642707-16648178;hs5:178951626-178952258,hs5:179071701-179076333;hs5:764765-772125,hs5:878460-880112;hs5:21453967-21456644,hs5:29418589-29426006;hs5:21569891-21573243,hs6:57573792-57575838;hs5:46380981-46387076,hs6:58775035-58779250;hs5:46390880-46404820,hs6:58775280-58779213;hs5:46352460-46367561,hs6:58776269-58779242;hs5:49529419-49547514,hs6:58774512-58779259;hs5:138181780-138186336,hs7:61968149-61970360;hs5:71146752-71146897,hs9:79186737-79186840;hs5:29788051-29788051,hs9:115921049-115921055;hs5:159349861-159351145,hsX:66979918-66985258;hs5:32370430-32370449,hsY:10019245-10026501;hs6:58773710-58779801,hs6:61900453-61916757;hs6:167585297-167602862,hs6:167781424-167797187;hs6:167603734-167609082,hs6:167770183-167777162;hs6:167580071-167583648,hs6:167798395-167806909;hs6:57742533-57753249,hs6:58352243-58358849;hs6:57725783-57743517,hs6:58330497-58348670;hs6:57753077-57760094,hs6:58362255-58364862;hs6:57937000-57946698,hs6:58540524-58548942;hs6:57920406-57933685,hs6:58521914-58536965;hs6:26740095-26745699,hs6:58146777-58152733;hs6:57819681-57828624,hs6:58429747-58436694;hs6:26670418-26678883,hs6:58192597-58198961;hs6:58021980-58040326,hs6:58702915-58718178;hs6:167615771-167627404,hs6:167725223-167737694;hs6:57795475-57807012,hs6:58398304-58415763;hs6:26699076-26706417,hs6:58164322-58170094;hs6:58046539-58055521,hs6:58686830-58695762;hs6:26689201-26694913,hs6:58175311-58179230;hs6:58615524-58627218,hs6:62075620-62085190;hs6:58594144-58601706,hs6:62060366-62072554;hs6:58647901-58656015,hs6:62107342-62116969;hs6:153742684-153746323,hs6:161206867-161209305;hs6:32599094-32606946,hs6:32705187-32712996;hs6:58075484-58076149,hs6:62126482-62127463;hs6:26665146-26667796,hs6:26799599-26804453;hs6:58776567-58779178,hs6:121376923-121381565;hs6:58773616-58779838,hs7:61967412-61989563;hs6:58773861-58779792,hs7:61990857-61999336;hs6:58773679-58779258,hs7:62000017-62009825;hs6:58773868-58779262,hs7:61079037-61099662;hs6:58776934-58778908,hs7:57971124-57979786;hs6:58774518-58779214,hs7:57954435-57965522;hs6:58773907-58778923,hs7:62030428-62043690;hs6:61910900-61918231,hs7:61967395-61972349;hs6:58776101-58778972,hs7:61783275-61804127;hs6:58776228-58779216,hs7:61752951-61759963;hs6:58773642-58778882,hs7:107410605-107411625;hs6:45295293-45299133,hs7:61969489-61970357;hs6:58773890-58779242,hs8:43790074-43799155;hs6:58773769-58779122,hs8:43817301-43819331;hs6:58777324-58779136,hs8:43820725-43831558;hs6:58773853-58779242,hs8:43092766-43096710;hs6:58776560-58779163,hs8:43782858-43789909;hs6:58776516-58779168,hs8:43770021-43775167;hs6:119558567-119558678,hs8:70602320-70602568;hs6:58775380-58779174,hs8:46881030-46890585;hs6:58776715-58779187,hs8:46896496-46907514;hs6:71872686-71879103,hs8:54959715-54961757;hs6:58775383-58778200,hs8:79308787-79316359;hs6:58776575-58779808,hs8:50602127-50615355;hs6:92870552-92870554,hs8:126745702-126745702;hs6:58776235-58779803,hs9:66821828-66826253;hs6:58776712-58779247,hs9:69986413-69989624;hs6:58776584-58779028,hs9:69945936-69958138;hs6:58773862-58779029,hs9:68414029-68425556;hs6:58777440-58779222,hs9:67317331-67317336;hs6:58773647-58779234,hsX:61820617-61848874;hs6:119558566-119558677,hsX:136520390-136520544;hs6:58774507-58779803,hsX:61860308-61868139;hs6:58773637-58779236,hsX:61720198-61735449;hs6:58776236-58779247,hsX:61742703-61749709;hs6:58777093-58779261,hsX:61750106-61768599;hs6:58773773-58778534,hsX:61770992-61774648;hs6:58777381-58779083,hsX:61907442-61907467;hs6:58774503-58778681,hsX:58556409-58563243;hs6:119558572-119558669,hsX:108297368-108297728;hs6:58775348-58779135,hsX:13334450-13342215;hs6:58773864-58779251,hsY:13460426-13488270;hs6:58776904-58778982,hsY:13451221-13457968;hs6:58774501-58779225,hsY:58973041-58997082;hs6:58776693-58779811,hsY:13852640-13869440;hs6:58776492-58779050,hsY:10019103-10032640;hs7:149850225-149873666,hs7:153488146-153509061;hs7:149608533-149624923,hs7:152462738-152481040;hs7:149631062-149645464,hs7:153843711-153858303;hs7:149874347-149881547,hs7:153477247-153487291;hs7:149700352-149700809,hs7:153787499-153789212;hs7:149714373-149727711,hs7:153761121-153777626;hs7:149590390-149597041,hs7:152488199-152498162;hs7:64521570-64541118,hs7:65217816-65233226;hs7:149586067-149589239,hs7:152495225-152498620;hs7:149772675-149790072,hs7:153707022-153719428;hs7:149681814-149686967,hs7:153802021-153809788;hs7:149821976-149836624,hs7:153660770-153674167;hs7:149651420-149679273,hs7:153810771-153838929;hs7:149804562-149814441,hs7:153681113-153689653;hs7:76759491-76768394,hs7:102373091-102382089;hs7:33010333-33020348,hs7:55777021-55784882;hs7:33025663-33033067,hs7:55761905-55770788;hs7:149746923-149754381,hs7:153741213-153748000;hs7:66718536-66731808,hs7:72015179-72025464;hs7:32999999-33010332,hs7:55788165-55794419;hs7:76777130-76785978,hs7:102352092-102363000;hs7:32815918-32825644,hs7:34905375-34912841;hs7:76700773-76711828,hs7:102428118-102439897;hs7:76720249-76729587,hs7:102414103-102419433;hs7:56800417-56808773,hs7:63299031-63309631;hs7:65070057-65082683,hs7:126543869-126558970;hs7:35086906-35096143,hs7:102803404-102811086;hs7:64470209-64480022,hs7:65313629-65318626;hs7:63503991-63512212,hs7:63774273-63779122;hs7:63518475-63526138,hs7:63786611-63793478;hs7:32671945-32686417,hs7:35008543-35020189;hs7:76126603-76131257,hs7:76626341-76632817;hs7:33039991-33049562,hs7:55748014-55752927;hs7:56844966-56852970,hs7:63253695-63263837;hs7:66584468-66599039,hs7:72145410-72159981;hs7:32703189-32720697,hs7:35035447-35053234;hs7:66667080-66678182,hs7:72066948-72077117;hs7:64564854-64566423,hs7:65261391-65262727;hs7:56832183-56839838,hs7:63263321-63273464;hs7:57119196-57125886,hs7:62975591-62981558;hs7:22552113-22559472,hs7:89764314-89770682;hs7:61054803-61059453,hs7:61672187-61675589;hs7:5918040-5929352,hs7:97611202-97619487;hs7:149893812-149899868,hs7:153460839-153468343;hs7:32807567-32811842,hs7:34891401-34901088;hs7:57548075-57555695,hs7:61780135-61798687;hs7:32828561-32837011,hs7:34929660-34933405;hs7:149970974-149976606,hs7:152529635-152534239;hs7:149985468-149991477,hs7:152515381-152519506;hs7:5193281-5205681,hs7:5840515-5855301;hs7:57113227-57117913,hs7:62985479-62989337;hs7:57546514-57555691,hs7:61740044-61757188;hs7:57695661-57703387,hs7:57883704-57892204;hs7:61054558-61056473,hs7:61748200-61760864;hs7:39906482-39912201,hs7:55736242-55743860;hs7:149928129-149936096,hs7:153425674-153432581;hs7:5168819-5174289,hs7:5872793-5874811;hs7:29728545-29739004,hs7:32755545-32762269;hs7:66189666-66197540,hs7:73375825-73384389;hs7:5946786-5956014,hs7:6848913-6856333;hs7:57546124-57556777,hs7:64951412-64956506;hs7:29671110-29677695,hs7:29781655-29789182;hs7:56644781-56649680,hs7:63880085-63884897;hs7:55734429-55741988,hs7:56485475-56489761;hs7:39836003-39844062,hs7:51440609-51453287;hs7:56558025-56564328,hs7:57475873-57478988;hs7:22531077-22538063,hs7:89788102-89790115;hs7:61740680-61745946,hs7:61968786-61969273;hs7:32861026-32871020,hs7:34972167-34984464;hs7:5019298-5031408,hs7:5763371-5777799;hs7:57059413-57069754,hs7:63034331-63043341;hs7:61054336-61058101,hs7:61784335-61798789;hs7:66771410-66778947,hs7:99783852-99791451;hs7:99813523-99819301,hs7:99940340-99944265;hs7:17862594-17865534,hs7:61967568-61969518;hs7:22574197-22581493,hs7:89725625-89734508;hs7:66027967-66029457,hs7:66257163-66259015;hs7:56732653-56737554,hs7:63699145-63703459;hs7:57668445-57670211,hs7:57912426-57914137;hs7:55828982-55830560,hs7:65286566-65287402;hs7:61968948-61975044,hs8:43092871-43097729;hs7:61079042-61085260,hs8:46852453-46856625;hs7:97505279-97512083,hs8:12396439-12406600;hs7:61969209-61971070,hs8:43819069-43832762;hs7:61967407-61969516,hs8:46847674-46856612;hs7:142460137-142476526,hs9:33793778-33802039;hs7:142484114-142487856,hs9:33793078-33803615;hs7:142442713-142450124,hs9:33780179-33789703;hs7:142400725-142416083,hs9:33691150-33705741;hs7:142346305-142359350,hs9:33633789-33641228;hs7:58036613-58040356,hs9:66840656-66845888;hs7:152111248-152113276,hs9:44323760-44325431;hs7:147472697-147472701,hs9:128000529-128000529;hs7:61967419-61969522,hsX:61726665-61747029;hs7:148356824-148356828,hsX:136520392-136520540;hs7:61967407-61977029,hsY:13460469-13488140;hs7:57546071-57556710,hsY:58972953-58985050;hs7:61967420-61972967,hsY:58974076-58996046;hs7:57546118-57556252,hsY:13446427-13459308;hs7:151967566-151969317,hsY:59001137-59003001;hs8:43820179-43838801,hs8:46839586-46857400;hs8:2178158-2187344,hs8:2336719-2343760;hs8:2193259-2197936,hs8:2329280-2332638;hs8:7236738-7252747,hs8:7771097-7788379;hs8:7327156-7338699,hs8:7687364-7697549;hs8:7275258-7283770,hs8:7742535-7749809;hs8:11988077-11998336,hs8:12232042-12240797;hs8:6958854-6968496,hs8:12500231-12505482;hs8:6981380-6987156,hs8:12422282-12428009;hs8:43793176-43798870,hs8:46852446-46856807;hs8:39229528-39231867,hs8:39387318-39389441;hs8:8032383-8039439,hs8:12338905-12345836;hs8:7990438-8004217,hs8:12378961-12390417;hs8:7365611-7374469,hs8:7660845-7667697;hs8:7924729-7925623,hs8:12453746-12455014;hs8:82754639-82754769,hsX:136520403-136520543;hs8:13047298-13047303,hsX:136520431-136520540;hs8:52730997-52735348,hsY:10008355-10013311;hs8:43092876-43096985,hsY:13460316-13476359;hs8:43092882-43096093,hsY:58981183-58997107;hs8:146299318-146301387,hsY:9974154-9981911;hs9:66454723-66479702,hs9:68390005-68415886;hs9:66469930-66485799,hs9:68380112-68389951;hs9:66499688-66507908,hs9:68366239-68371740;hs9:68511295-68514068,hs9:69000069-69003439;hs9:33586452-33599094,hs9:38543972-38555275;hs9:44174332-44183469,hs9:66516246-66528474;hs9:45370296-45379088,hs9:66506889-66518834;hs9:66506895-66516323,hs9:68356203-68361275;hs9:33575232-33585429,hs9:38559106-38566857;hs9:66858099-66862505,hs9:68995916-69004519;hs9:97157799-97168025,hs9:99745192-99756343;hs9:97140901-97153387,hs9:99758995-99769599;hs9:68432764-68434470,hs9:70835777-70837280;hs9:96099549-96107844,hs9:96270338-96279026;hs9:136085412-136100709,hs9:138424016-138437770;hs9:38492029-38508975,hs9:99845832-99863151;hs9:97181293-97188866,hs9:99721248-99731630;hs9:68488176-68496717,hs9:68683400-68694657;hs9:44726829-44728318,hs9:47199294-47203994;hs9:86496644-86505316,hs9:88456163-88461434;hs9:44462855-44466782,hs9:66521337-66528659;hs9:45372268-45378361,hs9:68353476-68359969;hs9:41944448-41950553,hs9:66554966-66561716;hs9:33511534-33525149,hs9:99985188-99996502;hs9:43155132-43161121,hs9:44137442-44144062;hs9:90524729-90526610,hs9:90750292-90755789;hs9:97109260-97117714,hs9:99661767-99670681;hs9:95968377-95973485,hs9:124569409-124569428;hs9:66664555-66666357,hs9:69844135-69847060;hs9:94983902-94983902,hs9:122013387-122013392;hs9:6725140-6731258,hsX:135956032-135961496;hs9:68391569-68411058,hsY:9925680-9945939;hs9:66454721-66473743,hsY:9925825-9947172;hs9:141067021-141068144,hsY:9963367-9972631;hs9:141081474-141088057,hsY:9975169-9977895;hs9:68409961-68418692,hsY:10007965-10015927;hs9:66833153-66835059,hsY:13481311-13486044;hs10:42382808-42399681,hs10:42596694-42602555;hs10:42380238-42409691,hs10:42525831-42544622;hs10:38872096-38890630,hs10:42380241-42404663;hs10:38869123-38874548,hs10:42361460-42369635;hs10:42377883-42396876,hs10:42661444-42667534;hs10:38872134-38888731,hs10:42596694-42602126;hs10:42397863-42408663,hs10:42812937-42818181;hs10:42370230-42384705,hs10:42790598-42800158;hs10:38772606-38791729,hs10:42361437-42369605;hs10:38774213-38782789,hs10:42370727-42385206;hs10:38799893-38809972,hs10:42372864-42380234;hs10:38802845-38809533,hs10:42356457-42367117;hs10:39087612-39098517,hs10:42372864-42379091;hs10:39101302-39109493,hs10:42355163-42372864;hs10:38801509-38818597,hs10:42794240-42810058;hs10:39130343-39154755,hs10:42370516-42384720;hs10:81271197-81289730,hs10:81992668-82008077;hs10:38778893-38786684,hs10:42378353-42384884;hs10:29781383-29789892,hs10:30971454-30979556;hs10:46206266-46216360,hs10:51811941-51821810;hs10:46219741-46222256,hs10:51823210-51829576;hs10:43210879-43216158,hs10:45614296-45623704;hs10:43219027-43225725,hs10:45608341-45612704;hs10:47651165-47653000,hs10:51488019-51495207;hs10:81587461-81598375,hs10:89104693-89115119;hs10:29573942-29585554,hs10:30912886-30921138;hs10:38875813-38892071,hs10:42660119-42667488;hs10:38491044-38502869,hs10:42903143-42917639;hs10:38780005-38785450,hs10:127574523-127575751;hs10:38799895-38809542,hs10:127574506-127575988;hs10:38445305-38460730,hs10:42955493-42968536;hs10:27567463-27576630,hs10:28254121-28262646;hs10:29853495-29861128,hs10:30944686-30948028;hs10:135238749-135246016,hs10:135385087-135392302;hs10:27551560-27559853,hs10:28278978-28287162;hs10:81550491-81556544,hs10:89071703-89080703;hs10:29667046-29677250,hs10:30879852-30890617;hs10:29800273-29807240,hs10:30957629-30960557;hs10:46958769-46967577,hs10:88968273-88976386;hs10:38336632-38347732,hs10:43087349-43099029;hs10:17972051-17973689,hs10:18221553-18223193;hs10:26876292-26881134,hs10:27222363-27227700;hs10:42527245-42533264,hs10:42817391-42818294;hs10:52417486-52426294,hs10:81444234-81449634;hs10:81339886-81345258,hs10:81681783-81684171;hs10:88997966-88999487,hs10:89255868-89262534;hs10:38917604-38921505,hs10:42783763-42790833;hs10:6672738-6677975,hs10:6837818-6845307;hs10:5203792-5204513,hs10:5324717-5324823;hs10:47654606-47655644,hs10:48358554-48359253;hs10:42384683-42400620,hs11:51568400-51580940;hs10:42398599-42408292,hs11:48962661-48963878;hs10:42396846-42408664,hs11:50723439-50730544;hs10:42383528-42400325,hs11:12741497-12741505;hs10:42527430-42533363,hs11:48962782-48963878;hs10:37244068-37249742,hs11:80396060-80406122;hs10:87286559-87286564,hs11:107815010-107815010;hs10:42392713-42409682,hs12:34832879-34856054;hs10:42383542-42389031,hs12:34830841-34849252;hs10:42527216-42539173,hs12:34832851-34856054;hs10:42398618-42408288,hs12:38002238-38004781;hs10:42817219-42819930,hs12:34834403-34853642;hs10:42596893-42600546,hs12:34841466-34854535;hs10:15050285-15055846,hs12:8592541-8595481;hs10:67034852-67034852,hs12:56815049-56815053;hs10:127574628-127577165,hs13:20370431-20371504;hs10:42384698-42385220,hs14:28050157-28055787;hs10:42383077-42399490,hs16:33870827-33897958;hs10:42383317-42401830,hs16:46420191-46449776;hs10:42383301-42408290,hs16:46385818-46409677;hs10:42383602-42396877,hs16:46450067-46456074;hs10:42384489-42400210,hs16:46410080-46419526;hs10:38875541-38888697,hs16:46385919-46409672;hs10:38875537-38887975,hs16:46410071-46419926;hs10:98561327-98561502,hs16:33951061-33960083;hs10:42661541-42668453,hs16:46385805-46409545;hs10:38876340-38888594,hs16:46420315-46429696;hs10:42384293-42396887,hs16:34180679-34196966;hs10:38875719-38888395,hs16:46430013-46439414;hs10:42596800-42602383,hs16:33870840-33897625;hs10:38877539-38888741,hs16:46442812-46449929;hs10:42660791-42667324,hs16:46423418-46429895;hs10:38872125-38888348,hs16:33870852-33897451;hs10:38877682-38888611,hs16:46452517-46455503;hs10:42660911-42667550,hs16:46431463-46449661;hs10:42391030-42401922,hs16:33968548-33975850;hs10:42384709-42387303,hs16:33970074-33976224;hs10:42597001-42603774,hs16:46385967-46408643;hs10:42596806-42605815,hs16:34175622-34198924;hs10:43325652-43342266,hs16:33475909-33489988;hs10:42596786-42602716,hs16:46430020-46458734;hs10:42527398-42535489,hs16:46385916-46407673;hs10:42659773-42667644,hs16:33870840-33897740;hs10:42384180-42396607,hs16:46498233-46502125;hs10:38876334-38888595,hs16:34180147-34196765;hs10:42659137-42667532,hs16:34181182-34195459;hs10:35310581-35310639,hs16:33950158-33951071;hs10:76110140-76110140,hs16:62672953-62672958;hs10:42370645-42396152,hs17:25263281-25271235;hs10:56161407-56168273,hs17:25461626-25468897;hs10:42652951-42660772,hs17:25297421-25308231;hs10:38808032-38818050,hs17:25263838-25267868;hs10:57498579-57506240,hs17:22098186-22106842;hs10:42380248-42408279,hs18:18510937-18520308;hs10:42418271-42418633,hs18:18511385-18520003;hs10:42382776-42400372,hs18:105823-111718;hs10:135499010-135505653,hs18:101389-111699;hs10:42596809-42600524,hs18:18511072-18520071;hs10:42529293-42535488,hs18:18511861-18520292;hs10:60493-62022,hs18:12430-14138;hs10:42597127-42602120,hs18:107593-109276;hs10:18315868-18316867,hs18:61596184-61596881;hs10:42380793-42409679,hs19:27731808-27744415;hs10:42525861-42544650,hs19:27731956-27740548;hs10:42596890-42600153,hs19:27731880-27739346;hs10:42817324-42818086,hs19:27732009-27740198;hs10:42387290-42399048,hs19:24525937-24528445;hs10:42380261-42401832,hs2:92267638-92276704;hs10:42370254-42397138,hs2:89830484-89853221;hs10:42370235-42383508,hs2:89859052-89869451;hs10:98561326-98561508,hs2:133022264-133031698;hs10:42360116-42387304,hs2:89857341-89879901;hs10:42355029-42359521,hs2:89866697-89879879;hs10:42380901-42401958,hs2:92300701-92324813;hs10:42384487-42388093,hs2:92295459-92297951;hs10:42392711-42399437,hs2:92295915-92300959;hs10:42596817-42602843,hs2:92266598-92284338;hs10:39114683-39133418,hs2:89872081-89879888;hs10:39123631-39133262,hs2:89863461-89869436;hs10:39110212-39115043,hs2:89850149-89856563;hs10:39120501-39149083,hs2:89850173-89859261;hs10:39080237-39095800,hs2:89850149-89861360;hs10:39146405-39154257,hs2:89865678-89879601;hs10:42803695-42816870,hs2:89857192-89879901;hs10:42791092-42805605,hs2:89862505-89878484;hs10:39076693-39085395,hs2:89851165-89878775;hs10:42596880-42600154,hs2:89830486-89851640;hs10:38773490-38794588,hs2:89863785-89879879;hs10:42384702-42400015,hs2:133018880-133029186;hs10:39150250-39154764,hs2:89850886-89857015;hs10:43362969-43370995,hs2:91758424-91766783;hs10:38877285-38888725,hs2:89830461-89849561;hs10:38870796-38874570,hs2:89870055-89879901;hs10:38875611-38888348,hs2:92265627-92272526;hs10:42527213-42535061,hs2:92304335-92312166;hs10:35310577-35310621,hs2:133032643-133034750;hs10:42665737-42669950,hs2:89842203-89848757;hs10:99292372-99292385,hs2:133018707-133024110;hs10:42661958-42667301,hs2:92268149-92269476;hs10:42384169-42387291,hs2:183640151-183648447;hs10:42531839-42534719,hs2:38080899-38081909;hs10:42360558-42383517,hs20:29809477-29829893;hs10:42355170-42358369,hs20:29821409-29832831;hs10:39118044-39129950,hs20:29817129-29825905;hs10:39101973-39113999,hs20:29813738-29822021;hs10:39132222-39141967,hs20:29803928-29812751;hs10:39135792-39145149,hs20:29815231-29829359;hs10:42383316-42399456,hs20:26305719-26319397;hs10:38772608-38784860,hs20:29804409-29813848;hs10:38803757-38817518,hs20:26199866-26201987;hs10:38868862-38874548,hs20:29805597-29817785;hs10:42362245-42388938,hs21:10800611-10828952;hs10:42355156-42365156,hs21:10814022-10827148;hs10:42371262-42380602,hs21:10850685-10855767;hs10:38813085-38818369,hs21:10830734-10835461;hs10:38800456-38817314,hs21:10820059-10829113;hs10:42384704-42387458,hs21:10855260-10856042;hs10:38772688-38781521,hs21:10812950-10821300;hs10:39105189-39111362,hs21:10848296-10858372;hs10:39118071-39124696,hs21:10830778-10838345;hs10:39119074-39127349,hs21:10774367-10782626;hs10:39077130-39090652,hs21:10795829-10809215;hs10:39085242-39098322,hs21:10823881-10846084;hs10:42390707-42401486,hs21:10701146-10716434;hs10:38870699-38879571,hs21:10783287-10793089;hs10:42383502-42398603,hs22:16847898-16862380;hs10:42596731-42602856,hs22:16849564-16862334;hs10:38875522-38893308,hs22:16848135-16869459;hs10:42660273-42669279,hs22:16848293-16864977;hs10:38975949-38985688,hs22:16951427-16958724;hs10:42383705-42398613,hs3:196625466-196625737;hs10:135441949-135465114,hs3:75690111-75710848;hs10:135440195-135441421,hs3:75715193-75716207;hs10:135461539-135469412,hs3:75680238-75689510;hs10:42398549-42408671,hs3:90492055-90498842;hs10:42384589-42394437,hs3:90453001-90462952;hs10:42596883-42600158,hs3:196625629-196625727;hs10:42384189-42390415,hs3:157641598-157647469;hs10:42360118-42387677,hs4:49631639-49659721;hs10:42354996-42359689,hs4:49634712-49659744;hs10:42384251-42409677,hs4:68261221-68269431;hs10:42355010-42379931,hs4:49100554-49126758;hs10:42355594-42379899,hs4:49134872-49159763;hs10:42380126-42387305,hs4:49100399-49122400;hs10:42380122-42387304,hs4:49146829-49156441;hs10:42362698-42379927,hs4:49093405-49099699;hs10:42525847-42539713,hs4:68264258-68266500;hs10:38773069-38782778,hs4:49633988-49648426;hs10:135443096-135450530,hs4:190952613-190959991;hs10:42804692-42816870,hs4:49653215-49659580;hs10:135455238-135459487,hs4:190961343-190966852;hs10:39139466-39154272,hs4:49116401-49126754;hs10:38812149-38817915,hs4:49108920-49116084;hs10:39144499-39154755,hs4:49148154-49158592;hs10:42790179-42799744,hs4:49147534-49156590;hs10:38775312-38782779,hs4:49146830-49157454;hs10:38813310-38815474,hs4:49146831-49156590;hs10:39090720-39101982,hs4:49148154-49156934;hs10:57519987-57523110,hs4:105026315-105029646;hs10:38869902-38874548,hs4:49145684-49156911;hs10:42384493-42389292,hs4:118009520-118015526;hs10:55793307-55794403,hs4:105744464-105745566;hs10:57524505-57525870,hs4:102286168-102287422;hs10:57521312-57522949,hs4:105745931-105746562;hs10:55791311-55792236,hs4:104739491-104740824;hs10:55793889-55795583,hs4:105035262-105036444;hs10:42396850-42403116,hs5:46334196-46340415;hs10:58478622-58483463,hs5:137841806-137842489;hs10:42380141-42409700,hs6:58773625-58780119;hs10:42527399-42535473,hs6:58773645-58779142;hs10:42596726-42605616,hs6:58773862-58779814;hs10:42815385-42818171,hs6:58773876-58779128;hs10:42396150-42409264,hs6:61908462-61914293;hs10:38872130-38883123,hs6:58773884-58779263;hs10:42662162-42666905,hs6:58776557-58779239;hs10:42380242-42409203,hs7:61967148-61989900;hs10:42396871-42402087,hs7:61990861-61992529;hs10:42383523-42400369,hs7:61780064-61802353;hs10:42524403-42539711,hs7:61967157-61989246;hs10:42383507-42399676,hs7:61739017-61759192;hs10:42381593-42396890,hs7:57545882-57555692;hs10:42635118-42649452,hs7:61815102-61833946;hs10:42596879-42600206,hs7:61967565-61973046;hs10:38874814-38888449,hs7:61780070-61802533;hs10:38872254-38887955,hs7:61738432-61758107;hs10:42596799-42601502,hs7:61780230-61802670;hs10:42596846-42603955,hs7:61739840-61759614;hs10:42660103-42667543,hs7:61780435-61799892;hs10:42392685-42404245,hs7:61079664-61083658;hs10:42659034-42668257,hs7:61739092-61755807;hs10:42596755-42601015,hs7:57543903-57556584;hs10:38873769-38888639,hs7:61968079-61970373;hs10:42383084-42387297,hs7:61080417-61092408;hs10:38873420-38887458,hs7:57546563-57555690;hs10:42817206-42818271,hs7:61968931-61979238;hs10:42383300-42399462,hs7:61054336-61055774;hs10:42647097-42653995,hs7:53219342-53226303;hs10:42660763-42666908,hs7:57546742-57555671;hs10:42383925-42400209,hs8:43092874-43097265;hs10:42398543-42403119,hs8:46861525-46861543;hs10:42384704-42391479,hs8:46852447-46858037;hs10:42384708-42398618,hs8:43793182-43795326;hs10:42384711-42404397,hs8:43817488-43825824;hs10:42527974-42532730,hs8:43790235-43798880;hs10:42528061-42538965,hs8:43092888-43096226;hs10:42596731-42600153,hs8:43092884-43095911;hs10:91786-101666,hs9:141065295-141072908;hs10:107194-117458,hs9:141044940-141055033;hs10:42844614-42856322,hs9:69823336-69834393;hs10:42355768-42365158,hs9:72653113-72653308;hs10:42393383-42400372,hsX:61749829-61759855;hs10:42395999-42408668,hsX:61726048-61736200;hs10:42527422-42535061,hsX:61728840-61736170;hs10:53722539-53724816,hsX:151240120-151245407;hs10:127581260-127609433,hsY:59010299-59033206;hs10:127608215-127616864,hsY:59001635-59011723;hs10:127592794-127598590,hsY:59010864-59016253;hs10:42381761-42400631,hsY:13460420-13487435;hs10:42370040-42387427,hsY:13451456-13461085;hs10:135499106-135502904,hsY:13460429-13489386;hs10:42360178-42369689,hsY:13450409-13459309;hs10:39120300-39149957,hsY:13840027-13869705;hs10:39150317-39154796,hsY:13842572-13856668;hs10:39136693-39149976,hsY:13830026-13839635;hs10:39120306-39127849,hsY:13830239-13842009;hs10:39120604-39141402,hsY:13820000-13829449;hs10:39120310-39147990,hsY:13810251-13819986;hs10:39100489-39119433,hsY:13810738-13830827;hs10:39100143-39119348,hsY:13833313-13839306;hs10:39076898-39099261,hsY:13840829-13869974;hs10:42360338-42385550,hsY:13842699-13860352;hs10:42361487-42375851,hsY:13865543-13869826;hs10:39080105-39100382,hsY:13808351-13828079;hs10:39100503-39117777,hsY:13854335-13869446;hs10:42355170-42373448,hsY:13836339-13846460;hs10:39111250-39139519,hsY:13671353-13689620;hs10:42355028-42359921,hsY:13448301-13461995;hs10:39100502-39122585,hsY:13660528-13688187;hs10:39120508-39141415,hsY:13650544-13663153;hs10:39077521-39079592,hsY:13813130-13823862;hs10:39077267-39079445,hsY:13801064-13802876;hs10:42384240-42399444,hsY:58972959-58997533;hs10:42356387-42359749,hsY:13850445-13858660;hs10:98561325-98561500,hsY:10017820-10023923;hs10:42374614-42379892,hsY:58973095-58980667;hs10:42378819-42385174,hsY:13810830-13822386;hs10:135499405-135502885,hsY:58979177-58997276;hs10:39131761-39149351,hsY:13453218-13461222;hs10:39120288-39126793,hsY:13449671-13459541;hs10:42370516-42379906,hsY:13680745-13688188;hs10:39077612-39081582,hsY:13674618-13687540;hs10:42373929-42380889,hsY:13701409-13709196;hs10:38809379-38818196,hsY:13864861-13869853;hs10:38793888-38799193,hsY:13857415-13869434;hs10:39085953-39109135,hsY:58972554-58982023;hs10:39123515-39149326,hsY:58971991-58981138;hs10:38778104-38790564,hsY:13449332-13459263;hs10:42809803-42815195,hsY:13810864-13824706;hs10:42355481-42359069,hsY:58974182-58981762;hs10:42382859-42396598,hsY:13640553-13646903;hs10:42795877-42808778,hsY:13800116-13805640;hs10:39091143-39104870,hsY:13446564-13450038;hs10:42803631-42807948,hsY:58971377-58979997;hs10:42361473-42380492,hsY:58827304-58827344;hs10:42660770-42669817,hsY:13639597-13645452;hs10:42355609-42372876,hsY:58854623-58857333;hs10:42596726-42600031,hsY:13479598-13485543;hs10:42361706-42369306,hsY:13137409-13141685;hs10:38869036-38874548,hsY:13834669-13856338;hs10:38869710-38874936,hsY:58973157-58978666;hs11:1615361-1623335,hs11:71271776-71279620;hs11:49235249-49251092,hs11:89350897-89362982;hs11:49224355-49235177,hs11:89366566-89374860;hs11:49762659-49789048,hs11:88591701-88619554;hs11:48386545-48388853,hs11:50036773-50039311;hs11:49754431-49759856,hs11:88621711-88627137;hs11:49712614-49727020,hs11:88644269-88664130;hs11:48851346-48859578,hs11:51567274-51579601;hs11:49672747-49696260,hs11:88675323-88698891;hs11:49708610-49709795,hs11:88661992-88667689;hs11:49170933-49193446,hs11:89407540-89426939;hs11:48504715-48527100,hs11:51440662-51468221;hs11:49269680-49276770,hs11:89320155,89328247;hs11:48639939-48647940,hs11:51398404-51405541;hs11:49128251-49137998,hs11:89450454-89460593;hs11:49473085-49480686,hs11:88973826-88985999;hs11:49438320-49450722,hs11:89007321-89014600;hs11:49418528-49424296,hs11:89028163-89037894;hs11:48466302-48476257,hs11:51496039-51505705;hs11:48452306-48462724,hs11:51509287-51517251;hs11:3486183-3493804,hs11:67603638-67610495;hs11:49564500-49572033,hs11:88807841-88814510;hs11:50097706-50106525,hs11:50288206-50301656;hs11:49362256-49367791,hs11:89095955-89102670;hs11:48541584-48548813,hs11:51426695-51433547;hs11:48435151-48444037,hs11:51526082-51534383;hs11:49341453-49349286,hs11:89115349-89123646;hs11:49310072-49319935,hs11:89146240-89152443;hs11:48746391-48750896,hs11:54892129-54892808;hs11:49976537-49987364,hs11:51487004-51493615;hs11:48982374-48989474,hs11:49841602-49845049;hs11:1617641-1621072,hs11:71236980-71237371;hs11:63673779-63673779,hs11:103893642-103893648;hs11:85195010-85195138,hs12:20704372-20704436;hs11:51572686-51580942,hs14:19013780-19015255;hs11:16697403-16701159,hs15:45035492-45040652;hs11:85195031-85195138,hs16:33963630-33964927;hs11:48761895-48764336,hs16:33973276-33981111;hs11:54914026-54920292,hs16:33969782-33977006;hs11:54990040-54993262,hs16:33973744-33975979;hs11:48894782-48899238,hs16:34021511-34022726;hs11:95899277-95899298,hs16:33955436-33960758;hs11:51567273-51585327,hs17:22247131-22262848;hs11:62609119-62609226,hs17:41400013-41401144;hs11:95899275-95899293,hs17:45212911-45213142;hs11:48852620-48867802,hs18:18511382-18520295;hs11:48840401-48849060,hs18:18513271-18519892;hs11:48883270-48899239,hs18:18511998-18520294;hs11:55008950-55027215,hs18:18512311-18520251;hs11:48810265-48810674,hs18:18511067-18520277;hs11:54992345-55001106,hs18:18512018-18519921;hs11:50760120-50771804,hs18:18513023-18520289;hs11:50778555-50783592,hs18:18511373-18520272;hs11:48935587-48943905,hs18:18511387-18519676;hs11:134820268-134834175,hs18:14955415-14968516;hs11:134840315-134844401,hs18:14947859-14953713;hs11:51567877-51579597,hs18:18516330-18520267;hs11:50668658-50678965,hs18:18517580-18520282;hs11:134857166-134864762,hs18:14901528-14909425;hs11:51568556-51579510,hs18:108030-108886;hs11:85195029-85195172,hs19:24183645-24184115;hs11:37754462-37754462,hs19:55573475-55573478;hs11:85195020-85195173,hs2:133038152-133039034;hs11:85195029-85195141,hs2:133011920-133012561;hs11:85195041-85195177,hs2:230045476-230045592;hs11:48892975-48899236,hs2:92303997-92309692;hs11:48891668-48895104,hs2:92316217-92325755;hs11:60214597-60214640,hs2:133016864-133019213;hs11:48856223-48864643,hs2:92274847-92281260;hs11:48810278-48815396,hs2:92273398-92281304;hs11:48893050-48894791,hs2:133002458-133003301;hs11:57222871-57222881,hs2:133026763-133031566;hs11:43653101-43653163,hs2:133022658-133030962;hs11:8484129-8484149,hs2:133021767-133029252;hs11:95899274-95899290,hs2:133021987-133027484;hs11:11370869-11376463,hs20:469373-470477;hs11:51568402-51579605,hs21:14341008-14353297;hs11:177739-183872,hs3:197893709-197899720;hs11:67541973-67549048,hs3:129799716-129808363;hs11:126667495-126671924,hs3:75429158-75429181;hs11:71588805-71594513,hs4:9445133-9450930;hs11:67540950-67545906,hs4:9718370-9724938;hs11:57222873-57222880,hs4:80273709-80274519;hs11:85195012-85195173,hs5:71146733-71146906;hs11:55008289-55026348,hs6:58773708-58780119;hs11:48831551-48839683,hs6:58773865-58779082;hs11:48850514-48859571,hs6:58774988-58779234;hs11:48860166-48867960,hs6:58776237-58779868;hs11:51566823-51580958,hs6:58773864-58780119;hs11:48881124-48899139,hs6:58776242-58779795;hs11:48940537-48963801,hs6:58773882-58779241;hs11:50686416-50699374,hs6:58773780-58779796;hs11:50762156-50771742,hs6:58777294-58779121;hs11:50778624-50783451,hs6:58776801-58778884;hs11:121230012-121236025,hs6:129477678-129480627;hs11:6720092-6726275,hs6:47253833-47255996;hs11:51566082-51580936,hs7:61967407-61971264;hs11:67508490-67519614,hs7:6926909-6933556;hs11:12741498-12743651,hs7:61968227-61979553;hs11:38809525-38815201,hs8:52730164-52731414;hs11:100981467-100981467,hs8:126145179-126145184;hs11:129693286-129705321,hs9:33758316-33770291;hs11:129535354-129542829,hs9:33708410-33713302;hs11:51568136-51582409,hsX:58557837-58567275;hs11:51590549-51593123,hsX:58561352-58565027;hs11:51567299-51580924,hsX:61839277-61839305;hs11:51567534-51581619,hsX:61714011-61725640;hs11:48851343-48859631,hsX:58558368-58565001;hs11:48853193-48854817,hsX:61839287-61839312;hs11:48894782-48899239,hsX:61841911-61848720;hs11:51567829-51578755,hsX:61860047-61864309;hs11:113299782-113299782,hsX:145665453-145665458;hs11:70866563-70874500,hsY:13229020-13235478;hs11:70831487-70837929,hsY:13202400-13204428;hs11:85195055-85195138,hsY:10036454-10037835;hs11:60214603-60214627,hsY:10029505-10031763;hs11:8484125-8484143,hsY:10021721-10026639;hs12:131788194-131797394,hs12:132130236-132143915;hs12:9601507-9629256,hs12:31201199-31226163;hs12:131810900-131814878,hs12:132116590-132122031;hs12:131778268-131783723,hs12:132144667-132149548;hs12:131794903-131797400,hs12:132126890-132129074;hs12:9627043-9632247,hs12:31193606-31199535;hs12:131823161-131833903,hs12:132104928-132110454;hs12:104373656-104382430,hs12:125798547-125803633;hs12:131775334-131779711,hs12:132150917-132155692;hs12:9699394-9708992,hs12:31284177-31296072;hs12:131705386-131714255,hs12:131921266-131926178;hs12:34163568-34178622,hs12:38695692-38714919;hs12:34152227-34159680,hs12:38684936-38695722;hs12:131715749-131722791,hs12:131910250-131916956;hs12:131697967-131702909,hs12:131929871-131934459;hs12:131749305-131757433,hs12:131885637-131889045;hs12:9456890-9466280,hs12:9570248-9582462;hs12:34838940-34850917,hs12:38002227-38008158;hs12:25956368-25957791,hs12:125800412-125803569;hs12:7989574-7994396,hs12:8104479-8109320;hs12:131553786-131556648,hs12:132041364-132047882;hs12:34244122-34253642,hs12:38856037-38867244;hs12:19468185-19470279,hs12:19578011-19579847;hs12:107676600-107678052,hs13:32328317-32328937;hs12:73236914-73242294,hs15:94886308-94888487;hs12:5775692-5784529,hs15:22491161-22501447;hs12:56989739-56990054,hs15:39992393-39997468;hs12:7942214-7947893,hs15:35373508-35379944;hs12:38444773-38450017,hs16:33952323-33958975;hs12:38444772-38445633,hs17:45212909-45221254;hs12:20704375-20704457,hs17:33478148-33478326;hs12:37990180-38018246,hs18:18511053-18520294;hs12:38023704-38029462,hs18:18512853-18520271;hs12:38116993-38123315,hs18:18512852-18520248;hs12:34831760-34854547,hs18:18511371-18520294;hs12:38030915-38038335,hs18:18516546-18520267;hs12:38063832-38070728,hs18:18513252-18520289;hs12:71427005-71427007,hs18:32800674-32800674;hs12:34830293-34855649,hs19:27731929-27740198;hs12:34372607-34372642,hs19:36066503-36066714;hs12:34372603-34372629,hs19:24184073-24184116;hs12:127650485-127650952,hs19:36066503-36066692;hs12:127650473-127650941,hs19:24183656-24184103;hs12:38444772-38450015,hs2:133019907-133033490;hs12:124496148-124499796,hs2:3929020-3933622;hs12:127650473-127650950,hs2:133034444-133039036;hs12:127650475-127650952,hs2:230045488-230045587;hs12:123889465-123895337,hs2:91931983-91938833;hs12:34372605-34372643,hs2:230045486-230045587;hs12:79839-86645,hs2:114344930-114352240;hs12:34372605-34372639,hs2:133034608-133039027;hs12:37998259-37998279,hs2:92272940-92276364;hs12:133343967-133344000,hs2:133018891-133024083;hs12:34389116-34393184,hs2:38936503-38940997;hs12:50129356-50129360,hs2:133021988-133029373;hs12:98495320-98495326,hs2:133025687-133031221;hs12:167303-171265,hs20:62962584-62965385;hs12:54505151-54519557,hs20:29557784-29567838;hs12:37896854-37912155,hs20:25927584-25945365;hs12:37856833-37873326,hs20:29432773-29452943;hs12:37901278-37908938,hs20:29479354-29487843;hs12:20704360-20704457,hs21:9825441-9827341;hs12:37856898-37865370,hs21:9415071-9427793;hs12:38187891-38197779,hs21:10698823-10711104;hs12:38503220-38515167,hs21:15471442-15479347;hs12:6125090-6132598,hs22:17174847-17180373;hs12:34321369-34348587,hs3:75730097-75757424;hs12:38576550-38594945,hs3:75739943-75756269;hs12:38584089-38593177,hs3:197841140-197846344;hs12:38480703-38484707,hs3:75679149-75686240;hs12:34833449-34855343,hs4:68264362-68266693;hs12:34372603-34372637,hs4:70296662-70296714;hs12:38583760-38592116,hs4:190913809-190919178;hs12:127650499-127650952,hs4:70296659-70296708;hs12:103492174-103494385,hs4:67661471-67667376;hs12:127650473-127650942,hs5:71146737-71146895;hs12:34832440-34855608,hs6:58773619-58779824;hs12:38026734-38039140,hs6:58773867-58779220;hs12:38013728-38021123,hs6:58777102-58778971;hs12:37991699-38010050,hs6:58773638-58779174;hs12:1896132-1898293,hs6:3018313-3024337;hs12:68444524-68449717,hs6:85577297-85580045;hs12:34372605-34372643,hs6:119558570-119558665;hs12:34832850-34854723,hs7:61967161-61986929;hs12:64111499-64119187,hs7:35271262-35283871;hs12:108200838-108206666,hs7:111053201-111053684;hs12:37857006-37859355,hs7:57750380-57752041;hs12:133828805-133835405,hs7:159098666-159105957;hs12:53432182-53434526,hs7:104307468-104313038;hs12:8316325-8325317,hs8:7222534-7227199;hs12:132926521-132926597,hs8:143265038-143269133;hs12:155854-164210,hs9:41803-49184;hs12:34340424-34344010,hs9:66463749-66471323;hs12:34339289-34346167,hs9:68393892-68401715;hs12:38002238-38009017,hsX:61726567-61734125;hs12:34834565-34849467,hsX:61725876-61731055;hs12:34320219-34335441,hsY:9950796-9974105;hs12:38580907-38595321,hsY:9951163-9968104;hs12:38443514-38450017,hsY:10020639-10028184;hs12:34340917-34348560,hsY:9932799-9939808;hs12:38567350-38580907,hsY:9932515-9944581;hs13:19951227-19977270,hs13:25001326-25025261;hs13:23505157-23528707,hs13:24925426-24948596;hs13:19915943-19925512,hs13:25111464-25118842;hs13:19903256-19913002,hs13:25130622-25138489;hs13:19942426-19953848,hs13:25039226-25049031;hs13:19781995-19785732,hs13:20290699-20296221;hs13:19770395-19784492,hs13:20274235-20286162;hs13:19936961-19943877,hs13:25051852-25054421;hs13:20120449-20126698,hs13:21842907-21849897;hs13:19992667-19997682,hs13:25169092-25173774;hs13:25572109-25580256,hs13:26644400-26654069;hs13:52861784-52864922,hs13:53093346-53098707;hs13:24462549-24468288,hs13:24891345-24898861;hs13:25565611-25568169,hs13:26672625-26679377;hs13:29783043-29788236,hs13:29916786-29923887;hs13:25596891-25603203,hs13:25735606-25741329;hs13:19982048-19988092,hs13:25511185-25518214;hs13:111604015-111610433,hs13:113047964-113055394;hs13:24984021-24993696,hs13:25549116-25557954;hs13:46982103-46988600,hs13:64356474-64359784;hs13:19798991-19805667,hs13:20319953-20327711;hs13:111597317-111601896,hs13:113084764-113090700;hs13:44066869-44072318,hs15:41853779-41871483;hs13:35682691-35692184,hs15:20865224-20877890;hs13:44068374-44071755,hs15:76551686-76553434;hs13:63600377-63623847,hs17:21666624-21685729;hs13:28033701-28034019,hs17:45234279-45235621;hs13:28033701-28033738,hs17:45247313-45249331;hs13:58066690-58066792,hs17:41399903-41400800;hs13:46948613-46948685,hs17:41400521-41400926;hs13:28033717-28034014,hs17:52387171-52387177;hs13:19193453-19203798,hs18:14431556-14441305;hs13:19179032-19191574,hs18:14441297-14455939;hs13:19223272-19229544,hs18:14402334-14408819;hs13:19261907-19269325,hs18:14362029-14372014;hs13:19248774-19255390,hs18:14376805-14383922;hs13:19477692-19483993,hs18:14639364-14644803;hs13:28033695-28034022,hs2:133008511-133020280;hs13:47111495-47111515,hs2:133028362-133034533;hs13:87100450-87100471,hs2:133025295-133025862;hs13:63646121-63648968,hs20:26146878-26149644;hs13:63635367-63637451,hs20:26146597-26148108;hs13:19276299-19284083,hs21:15175706-15184011;hs13:19287120-19294871,hs21:15186088-15190870;hs13:19300067-19306223,hs21:15204336-15208709;hs13:19243162-19259251,hs21:15140810-15150703;hs13:19443561-19447940,hs21:15338914-15347311;hs13:19144569-19151953,hs21:14572912-14581551;hs13:21923844-21933793,hs6:5816169-5824861;hs13:21896554-21901792,hs6:5852425-5855012;hs13:21819575-21823515,hs6:5584988-5590389;hs13:63647186-63648808,hs7:57605774-57608234;hs13:19641273-19648892,hs9:96382970-96387618;hs13:19648164-19653484,hs9:96374024-96378695;hs13:28033701-28034035,hsY:10028792-10029765;hs13:19968790-19974817,hsY:28755652-28762552;hs13:19946458-19952767,hsY:28778555-28780808;hs13:25000757-25010635,hsY:28755425-28759639;hs14:106039649-106055700,hs14:106157186-106173778;hs14:70711233-70716675,hs14:70920508-70928616;hs14:106073583-106084285,hs14:106191266-106201842;hs14:106077863-106083708,hs14:106220235-106226838;hs14:106535131-106542113,hs14:107162900-107176136;hs14:106932147-106934127,hs14:107170966-107178185;hs14:106689157-106693721,hs14:107178322-107184174;hs14:106896055-106902673,hs14:107181083-107187040;hs14:106647946-106654326,hs14:106839914-106846761;hs14:106732774-106733999,hs14:107148690-107149975;hs14:106472131-106486986,hs15:22467475-22483140;hs14:20226593-20242095,hs15:22341110-22358395;hs14:20242370-20249721,hs15:22362528-22369906;hs14:20247263-20259376,hs15:22367625-22378391;hs14:106481809-106484034,hs15:22486895-22489136;hs14:20263925-20268517,hs15:22381671-22388518;hs14:20213446-20218622,hs15:22331520-22336184;hs14:20205007-20215268,hs15:22320286-22329977;hs14:20196481-20205079,hs15:22314735-22320344;hs14:106460824-106470440,hs15:22456283-22463143;hs14:106633719-106650716,hs15:20171861-20186243;hs14:106451001-106456570,hs15:22444908-22450262;hs14:20284503-20304381,hs15:22404721-22422220;hs14:106441431-106445907,hs15:22433959-22439374;hs14:19102698-19108983,hs15:20078337-20083741;hs14:106767562-106773151,hs15:22486934-22490828;hs14:67511373-67512435,hs16:33954815-33960374;hs14:107215712-107221972,hs16:33625345-33632896;hs14:88237585-88237736,hs17:45249288-45249331;hs14:87520596-87520600,hs17:25263835-25267998;hs14:19000214-19026066,hs18:18511102-18520298;hs14:19036004-19039937,hs18:18512846-18520294;hs14:20321738-20329427,hs18:14581149-14585516;hs14:20310261-20316543,hs18:14564149-14577150;hs14:100416413-100421767,hs18:74964883-74964948;hs14:19010850-19024030,hs19:27732054-27740198;hs14:19000881-19020352,hs2:92294769-92309699;hs14:88237570-88237773,hs2:133016765-133019590;hs14:19008429-19021700,hs2:92272970-92281478;hs14:67511383-67512433,hs2:133021053-133029352;hs14:19000758-19023850,hs2:132997510-133004682;hs14:19032970-19044763,hs2:132975250-132983122;hs14:19467976-19472825,hs2:130694534-130699892;hs14:28232176-28239033,hs2:95364365-95372596;hs14:87520593-87520600,hs2:133024055-133029277;hs14:19014559-19026079,hs21:14344298-14355636;hs14:19078904-19087882,hs21:14379792-14388843;hs14:20310592-20320318,hs21:14951795-14956710;hs14:87520568-87520600,hs21:10781084-10792608;hs14:19787024-19795892,hs22:16050002-16057250;hs14:19150353-19154209,hs22:16670752-16675769;hs14:54328647-54334270,hs3:118716767-118720082;hs14:107215845-107215845,hs3:106724088-106724093;hs14:52665330-52666340,hs4:170281086-170281812;hs14:51130495-51131202,hs4:144833682-144834838;hs14:54360691-54360691,hs4:133133335-133133337;hs14:101020572-101020574,hs5:111357935-111357935;hs14:19020353-19024602,hs6:58773774-58779833;hs14:19029088-19045737,hs6:58774529-58779188;hs14:19000880-19009646,hs6:58773896-58779187;hs14:36477238-36477238,hs6:88654659-88654667;hs14:32402890-32402899,hs7:17864884-17864886;hs14:82886471-82886471,hs7:112497739-112497742;hs14:52981602-52981612,hs9:19962226-19962226;hs14:88237573-88237753,hsY:10029169-10031971;hs14:87520584-87520600,hsY:13449279-13459218;hs15:21148439-21167677,hs15:22156956-22178020;hs15:24564227-24578673,hs15:24773694-24788118;hs15:30977702-30986098,hs15:32002917-32014779;hs15:31000629-31009531,hs15:31981137-31989536;hs15:45120046-45124858,hs15:45359749-45362821;hs15:20876233-20892927,hs15:21885112-21900971;hs15:45126130-45133378,hs15:45352354-45357494;hs15:82510613-82516106,hs15:84786787-84789099;hs15:20847493-20850272,hs15:23512353-23514631;hs15:78288965-78293777,hs15:79040740-79047673;hs15:23171138-23183113,hs15:29005180-29018045;hs15:23160433-23167207,hs15:29025459-29029720;hs15:24419983-24428811,hs15:24635077-24643885;hs15:23153005-23159223,hs15:29030664-29037943;hs15:20935542-20940767,hs15:21939589-21945333;hs15:100330590-100341170,hs15:102303752-102312134;hs15:24410554-24417785,hs15:24625779-24630429;hs15:82534372-82544347,hs15:84762039-84768124;hs15:23134238-23140482,hs15:29052426-29055402;hs15:34713828-34727152,hs15:34860008-34874688;hs15:24357610-24364150,hs15:24520584-24529676;hs15:28378675-28384458,hs15:31133076-31138892;hs15:28391574-28395049,hs15:31120491-31128062;hs15:100322687-100333378,hs15:102323149-102329165;hs15:24503651-24515547,hs15:24671416-24680539;hs15:20625574-20633035,hs15:22589149-22595999;hs15:30915909-30928461,hs15:32907254-32920967;hs15:24421627-24429899,hs15:24807039-24816493;hs15:23095478-23102330,hs15:29088248-29092808;hs15:78272637-78278086,hs15:79060821-79066902;hs15:82484455-82494546,hs15:84810006-84815506;hs15:24452667-24457837,hs15:24554865-24562520;hs15:24504098-24510792,hs15:24722198-24726967;hs15:78236641-78243019,hs15:79040287-79042435;hs15:75975502-75980873,hs15:78188294-78195200;hs15:23098259-23100836,hs15:23685712-23693439;hs15:76029006-76032311,hs15:78196641-78202758;hs15:31057265-31062667,hs15:31925400-31930552;hs15:24617813-24625249,hs15:24792098-24797419;hs15:100981111-100988384,hs15:101616104-101617587;hs15:21203397-21204256,hs15:22297269-22298551;hs15:20430437-20457797,hs16:33400753-33428477;hs15:20463780-20469396,hs16:33391690-33396692;hs15:20466278-20476424,hs16:33384636-33389929;hs15:20423738-20426992,hs16:33431145-33435740;hs15:22544859-22558405,hs16:87511227-87525756;hs15:20479218-20488418,hs16:33371443-33383284;hs15:20410556-20418086,hs16:33440838-33449543;hs15:22516637-22530119,hs16:87551354-87559386;hs15:20394573-20408088,hs16:33447604-33465235;hs15:20554492-20562088,hs17:77685892-77688285;hs15:80445515-80445523,hs17:25264595-25267785;hs15:86440632-86440634,hs17:45212922-45213942;hs15:20029757-20037041,hs18:15387948-15397303;hs15:20454143-20470914,hs19:33490984-33506273;hs15:20591292-20616077,hs2:13531325-13554950;hs15:21914932-21929746,hs2:165838354-165849816;hs15:21903023-21914216,hs2:165830661-165837004;hs15:22580468-22590952,hs2:13508317-13518734;hs15:20563517-20572372,hs2:13589619-13595582;hs15:20068340-20075131,hs2:132930638-132939104;hs15:102502980-102503283,hs2:114340099-114344958;hs15:47348246-47366492,hs20:29457466-29475712;hs15:47394467-47399053,hs20:29420375-29428760;hs15:47352182-47368385,hs20:25906291-25920269;hs15:22787970-22794720,hs20:45019853-45026510;hs15:20150073-20155779,hs21:10879008-10886752;hs15:20157612-20170317,hs21:10860554-10878513;hs15:20105543-20122617,hs21:9440020-9458755;hs15:20012426-20015908,hs21:14359028-14361453;hs15:47383121-47393390,hs21:9422393-9431541;hs15:20488380-20499758,hs22:29078520-29090100;hs15:21929795-21937870,hs3:196552664-196559305;hs15:58007329-58009447,hs4:68903413-68910226;hs15:23100832-23109652,hs5:7298454-7305295;hs15:20002456-20014751,hs6:58776501-58779228;hs15:94254680-94254680,hs6:9979499-9979501;hs15:40851051-40856982,hs7:26241368-26252921;hs16:33870832-33899847,hs16:46385806-46409314;hs16:33870929-33890670,hs16:46410315-46419794;hs16:33872350-33897802,hs16:46411458-46429991;hs16:34178610-34196973,hs16:46385939-46409314;hs16:34182955-34196526,hs16:46410405-46419685;hs16:33893032-33897629,hs16:46430010-46439217;hs16:33870849-33886128,hs16:46430016-46439486;hs16:33878566-33885001,hs16:46440647-46448803;hs16:34181570-34196973,hs16:46420275-46429894;hs16:34179174-34196765,hs16:46430012-46449726;hs16:34178489-34188066,hs16:46450050-46456398;hs16:33878146-33887081,hs16:46450303-46456349;hs16:70128359-70139376,hs16:74560762-74570822;hs16:70111790-70127658,hs16:74574921-74589940;hs16:21591853-21594349,hs16:22707743-22710688;hs16:29228123-29241441,hs16:88216459-88230882;hs16:33878279-33894383,hs16:34180674-34194474;hs16:15101899-15112698,hs16:70055372-70068798;hs16:15115558-15123530,hs16:70043744-70054836;hs16:15256604-15277987,hs16:18165653-18186876;hs16:29246792-29254111,hs16:88236535-88248453;hs16:15313188-15317129,hs16:18223726-18231284;hs16:29163482-29177079,hs16:88150941-88163335;hs16:29181397-29189564,hs16:88167982-88179601;hs16:29156633-29165844,hs16:88142725-88148157;hs16:29202422-29207239,hs16:88190955-88195622;hs16:70151063-70158101,hs16:74393517-74398848;hs16:70159923-70173079,hs16:74375155-74386884;hs16:70177103-70185914,hs16:74365924-74370826;hs16:29313933-29322529,hs16:88042475-88049000;hs16:29322712-29330687,hs16:88053097-88061605;hs16:29280187-29287501,hs16:88275256-88283598;hs16:15298502-15304060,hs16:18210116-18215821;hs16:34389589-34392056,hs16:34754771-34757643;hs16:16722352-16727747,hs16:18733917-18734636;hs16:32367210-32372374,hs16:33366616-33370924;hs16:46386710-46397055,hs16:46498167-46500220;hs16:16290297-16296549,hs16:18603439-18607359;hs16:16690099-16699083,hs16:18762245-18766778;hs16:16630383-16637127,hs16:18261768-18269206;hs16:29121148-29129184,hs16:88010376-88021969;hs16:15074122-15079993,hs16:70090923-70095213;hs16:32352803-32361665,hs16:33352337-33361466;hs16:21781503-21787009,hs16:22598958-22605490;hs16:15372528-15379595,hs16:16565300-16568560;hs16:21534068-21538514,hs16:87910168-87916536;hs16:33951061-33957706,hs16:50817013-50817018;hs16:32954279-32959020,hs16:33711126-33716268;hs16:70228790-70233257,hs16:74428642-74432865;hs16:33954593-33961152,hs17:45212911-45221260;hs16:33959499-33961106,hs17:45232039-45235622;hs16:33865286-33868612,hs17:25264330-25269796;hs16:33899146-33902274,hs17:25263294-25267889;hs16:33830895-33836453,hs17:25271739-25277460;hs16:33846590-33847949,hs17:25281841-25287355;hs16:33963601-33964110,hs17:33478144-33478240;hs16:33575367-33587289,hs17:25291304-25302541;hs16:34021429-34022734,hs18:18511185-18520297;hs16:34013514-34016447,hs18:18512000-18520294;hs16:34000264-34004027,hs18:18512854-18520012;hs16:35215958-35239703,hs18:18511377-18520291;hs16:46386011-46407681,hs18:18511386-18520282;hs16:46424774-46429709,hs18:18511512-18520071;hs16:46431409-46438712,hs18:18513519-18520277;hs16:46386176-46407691,hs18:106801-109462;hs16:46385816-46408642,hs19:27731987-27740198;hs16:46420307-46429990,hs19:27732054-27740198;hs16:33952597-33958451,hs19:30777394-30777484;hs16:33951127-33963464,hs19:27731978-27738589;hs16:33947094-33968679,hs2:133010138-133035832;hs16:33963271-33978056,hs2:133002468-133009771;hs16:46385914-46409542,hs2:89830448-89855853;hs16:46410700-46419847,hs2:89832880-89849727;hs16:46420234-46429901,hs2:89831462-89849697;hs16:46430068-46439944,hs2:89830560-89850059;hs16:46440766-46449255,hs2:89841837-89846605;hs16:33526838-33545116,hs2:96604105-96623069;hs16:46386000-46408643,hs2:92267564-92276696;hs16:46417020-46419828,hs2:92268188-92271452;hs16:34179070-34195955,hs2:89831514-89849825;hs16:33871334-33898373,hs2:89831648-89848696;hs16:46420191-46429452,hs2:92267614-92270868;hs16:33533209-33552122,hs2:97806768-97827548;hs16:46386143-46407712,hs2:92316214-92324220;hs16:46432717-46439215,hs2:92267615-92272413;hs16:46400965-46408638,hs2:92303998-92309697;hs16:46448484-46458733,hs2:92265975-92272328;hs16:33870843-33896614,hs2:92266387-92272961;hs16:34175486-34193888,hs2:92265495-92271343;hs16:14580874-14580926,hs2:133030262-133035051;hs16:34021524-34022725,hs2:92304799-92309693;hs16:33953140-33960775,hs2:62957881-62959072;hs16:33953003-33957606,hs2:155511467-155511525;hs16:32470176-32485458,hs2:92030578-92046043;hs16:34020408-34022788,hs2:132996309-133003301;hs16:8516552-8516558,hs2:133025295-133031233;hs16:33952330-33957711,hs2:2299333-2299505;hs16:46495802-46500048,hs2:92267564-92270868;hs16:33529282-33533595,hs2:89069174-89073817;hs16:33953151-33960760,hs2:65832134-65832144;hs16:79527039-79527041,hs2:133022689-133023531;hs16:50817013-50817017,hs2:133026741-133030993;hs16:26587392-26587392,hs2:50316910-50316915;hs16:33957938-33959947,hs20:60924740-60924757;hs16:33963034-33963735,hs20:26188826-26189040;hs16:33952319-33960526,hs20:58139688-58140002;hs16:33970094-33988356,hs21:10698027-10719877;hs16:33961268-33965433,hs21:9825468-9827496;hs16:33865244-33868601,hs21:10780303-10807346;hs16:33915719-33920726,hs21:10706706-10716061;hs16:33898880-33903308,hs21:10797959-10807170;hs16:35265257-35273284,hs21:10762228-10766311;hs16:32817035-32817500,hs21:9440563-9446885;hs16:46385810-46409668,hs22:16848074-16862429;hs16:46410099-46419796,hs22:16850099-16862346;hs16:46420035-46429893,hs22:16848279-16862110;hs16:46430276-46439592,hs22:16848486-16861625;hs16:46441961-46449681,hs22:16849161-16861629;hs16:33885854-33897968,hs22:16848491-16861629;hs16:33870833-33883240,hs22:16857979-16863794;hs16:34180923-34195915,hs22:16848155-16862350;hs16:32454756-32466959,hs22:16887457-16902425;hs16:33933854-33947800,hs3:75716958-75720921;hs16:33953003-33960859,hs4:80273527-80274699;hs16:33865278-33868680,hs4:49635687-49659703;hs16:33963735-33969811,hs4:190632788-190638533;hs16:33944549-33947840,hs4:190939778-190942725;hs16:46386163-46395404,hs4:68264331-68266554;hs16:33866461-33866656,hs4:49147280-49156930;hs16:33969988-33977600,hs5:49540139-49551937;hs16:33435241-33444426,hs5:61534690-61541604;hs16:33952598-33957621,hs5:32369108-32370453;hs16:71325821-71326485,hs5:115249286-115249506;hs16:46386184-46409323,hs6:58773617-58779259;hs16:46410132-46419800,hs6:58776863-58779827;hs16:46420037-46429888,hs6:58773879-58779242;hs16:46432716-46439244,hs6:58776901-58779234;hs16:33951075-33965422,hs6:58775373-58779033;hs16:33971292-33978253,hs6:58773780-58779217;hs16:46451984-46456083,hs6:58776871-58778541;hs16:33889351-33899864,hs6:58776716-58779153;hs16:33871297-33881730,hs6:58776264-58778667;hs16:35232014-35239864,hs6:58777189-58779258;hs16:33930745-33949413,hs6:58773888-58779241;hs16:35276755-35284701,hs6:58773877-58779799;hs16:33949537-33950468,hs6:119558564-119558678;hs16:14580869-14580931,hs6:119558562-119558678;hs16:33426233-33428181,hs6:380534-382351;hs16:46390117-46419854,hs7:61780057-61803009;hs16:46385803-46389955,hs7:61781564-61802327;hs16:46420149-46429897,hs7:61780272-61802461;hs16:46430008-46439974,hs7:61784136-61802544;hs16:46440969-46449892,hs7:61782709-61802538;hs16:46390116-46419504,hs7:61739102-61759253;hs16:46386235-46389946,hs7:61740990-61748648;hs16:46385883-46408642,hs7:57546297-57556781;hs16:46410392-46417048,hs7:57546284-57555586;hs16:46420730-46429074,hs7:61739675-61758181;hs16:46431418-46439868,hs7:61738650-61758288;hs16:46450112-46456532,hs7:61782714-61802941;hs16:46441501-46449843,hs7:61747136-61759444;hs16:46386297-46407695,hs7:61967416-61973290;hs16:46421037-46429892,hs7:57546709-57554222;hs16:46450141-46456074,hs7:61739088-61758749;hs16:33878152-33899503,hs7:61780092-61802413;hs16:33870835-33874981,hs7:61783966-61798962;hs16:46430028-46439904,hs7:57542906-57555686;hs16:46420000-46429424,hs7:61967571-61970324;hs16:46440997-46449664,hs7:57550444-57557878;hs16:33876657-33897573,hs7:61737089-61758243;hs16:33879540-33886688,hs7:61750830-61758297;hs16:33883850-33899796,hs7:57546325-57555687;hs16:33870656-33874441,hs7:57547588-57558867;hs16:32491694-32510459,hs7:61850099-61869322;hs16:34178349-34195006,hs7:61748996-61759656;hs16:34181739-34194322,hs7:61742519-61748622;hs16:34180128-34196254,hs7:61780966-61802546;hs16:32847044-32855857,hs7:61824969-61832816;hs16:33864515-33868400,hs7:57546088-57555291;hs16:33954373-33971014,hs7:61968934-61975045;hs16:46386781-46409675,hs7:64953941-64954100;hs16:33969781-33976015,hs7:61535898-61547923;hs16:34181326-34190558,hs7:57546773-57555684;hs16:33039439-33045178,hs7:61815097-61820082;hs16:46386223-46396691,hs7:61054406-61055754;hs16:33883034-33899136,hs7:61968960-61973037;hs16:46496867-46500430,hs7:61744212-61758256;hs16:33581069-33587011,hs7:53226379-53233458;hs16:32093334-32099887,hs7:61818946-61827315;hs16:77007941-77007945,hs7:114783893-114783893;hs16:33937357-33944823,hs8:52730875-52733092;hs16:46400021-46408637,hs8:43092877-43096893;hs16:46386156-46394961,hs8:43092881-43097470;hs16:46423414-46429147,hs8:43092836-43095946;hs16:46431429-46439219,hs8:43092887-43095901;hs16:33954808-33960375,hs8:143336921-143337528;hs16:33936449-33949551,hs9:68409676-68418656;hs16:33502149-33507740,hs9:67331863-67339468;hs16:34021524-34022725,hs9:66800742-66800779;hs16:83946-86042,hs9:141034689-141036200;hs16:33971158-33975379,hsX:61903778-61915055;hs16:34021508-34022726,hsX:61841906-61849402;hs16:33952600-33960378,hsX:1259697-1260926;hs16:33950343-33952596,hsX:136520393-136520545;hs16:33932141-33959969,hsY:10002542-10028214;hs16:33954685-33969885,hsY:10020646-10039759;hs16:33967482-33977068,hsY:10040647-10048080;hs16:33921682-33929439,hsY:9991294-9999631;hs16:33887642-33888569,hsY:58973767-58983225;hs16:33865004-33871074,hsY:58972677-58983697;hs16:33544788-33555401,hsY:58967877-58973593;hs16:33535784-33559162,hsY:28573069-28588860;hs16:33865065-33867169,hsY:13446650-13453810;hs16:33895784-33902270,hsY:13445352-13459545;hs16:33887640-33893681,hsY:13448294-13459305;hs16:46400067-46408555,hsY:13465181-13468333;hs16:33898797-33902272,hsY:58973539-58988398;hs16:46386203-46396748,hsY:13642454-13644797;hs16:33865020-33867794,hsY:28784353-28791291;hs16:33865068-33868588,hsY:13138145-13143797;hs16:33897439-33903728,hsY:28784661-28789217;hs17:21330190-21355507,hs17:25310249-25336059;hs17:21326382-21329962,hs17:25310563-25314062;hs17:20767159-20782794,hs17:21506673-21521664;hs17:14084221-14098833,hs17:15481323-15495370;hs17:21249638-21254672,hs17:25332847-25337568;hs17:21547085-21558066,hs17:22206632-22218226;hs17:14076943-14079959,hs17:15475698-15479936;hs17:36369766-36384510,hs17:45635057-45649823;hs17:36350679-36356290,hs17:45664815-45669256;hs17:15586035-15599329,hs17:18590700-18605573;hs17:15571187-15577047,hs17:18611814-18619834;hs17:15443847-15458461,hs17:18692409-18704821;hs17:21379411-21388043,hs17:21980311-21985970;hs17:15730369-15741391,hs17:20548826-20561473;hs17:36360540-36368562,hs17:45655435-45659769;hs17:44366527-44369215,hs17:62916269-62918391;hs17:15720427-15727881,hs17:20538122-20546643;hs17:2969284-2978324,hs17:3132921-3143838;hs17:16065038-16073365,hs17:21540135-21550416;hs17:18285483-18296897,hs17:20454091-20464139;hs17:2978950-2984259,hs17:3123357-3129821;hs17:15760115-15766288,hs17:20575863-20581066;hs17:65852225-65856393,hs17:66206517-66216332;hs17:15493494-15499713,hs17:18668582-18676964;hs17:15504117-15510022,hs17:18660673-18667845;hs17:20734253-20739220,hs17:22034062-22041923;hs17:15628638-15635142,hs17:18545521-18554879;hs17:15638149-15643987,hs17:18536591-18548453;hs17:15708267-15713147,hs17:20512530-20522903;hs17:43660476-43661939,hs17:62916121-62917570;hs17:21485343-21490346,hs17:21806548-21815119;hs17:13921086-13927815,hs17:14142523-14144061;hs17:58289433-58299546,hs17:60368377-60377240;hs17:43650835-43655548,hs17:65828591-65835686;hs17:21497253-21505014,hs17:21796755-21802382;hs17:20650292-20654036,hs17:58031456-58036960;hs17:4539026-4547274,hs17:6556429-6564785;hs17:29065354-29075764,hs17:30272256-30282566;hs17:62992963-63002481,hs17:66216677-66225470;hs17:43651023-43653634,hs17:44567255-44569119;hs17:45213087-45213631,hs17:52387171-52387179;hs17:36297559-36307880,hs17:58452202-58457351;hs17:16717477-16717512,hs17:39728598-39729286;hs17:4306818-4306829,hs17:45234286-45235588;hs17:16581352-16586994,hs17:20806162-20812464;hs17:25278991-25296458,hs18:15192890-15208423;hs17:33478145-33478316,hs19:24183658-24184101;hs17:28975385-28980137,hs19:14396954-14400950;hs17:22253177-22253211,hs19:27873064-27873067;hs17:45234283-45235620,hs19:13091745-13091749;hs17:45212882-45221261,hs2:133015861-133029235;hs17:45234279-45235616,hs2:133015319-133022680;hs17:45247311-45249331,hs2:133016053-133021980;hs17:33478161-33478234,hs2:133038152-133038991;hs17:33478137-33478228,hs2:133011930-133012584;hs17:25292707-25298267,hs2:132785874-132793723;hs17:25263048-25267336,hs2:89866643-89879819;hs17:25299746-25306991,hs2:132779586-132782873;hs17:25283250-25290841,hs2:132797128-132803423;hs17:45212927-45213956,hs2:62957883-62957921;hs17:33478141-33478326,hs2:230045484-230045594;hs17:45212903-45213635,hs2:51581404-51581419;hs17:4306816-4306828,hs2:133019009-133019570;hs17:21531162-21557201,hs20:26070246-26099534;hs17:21520663-21532966,hs20:26101281-26108966;hs17:21544761-21556954,hs20:25734563-25744791;hs17:21506581-21519637,hs20:26113156-26128382;hs17:21558124-21566310,hs20:25752545-25762393;hs17:20764640-20784521,hs20:26110086-26130683;hs17:22205181-22216423,hs20:25738699-25744467;hs17:25263785-25266975,hs20:29811942-29824327;hs17:22206776-22211558,hs20:26074219-26081476;hs17:25263168-25269820,hs21:10780218-10809782;hs17:25263708-25267803,hs21:10773152-10779151;hs17:25281360-25292008,hs21:9474157-9482762;hs17:25271383-25278316,hs21:9462696-9471276;hs17:25289146-25306998,hs21:9440467-9455820;hs17:66309195-66309226,hs21:11186212-11188049;hs17:25264597-25267787,hs21:10085042-10087658;hs17:25281324-25286593,hs21:10888391-10891089;hs17:66309191-66309227,hs22:18878228-18884393;hs17:41381670-41382391,hs3:73159921-73160234;hs17:41399748-41400866,hs3:73159901-73160076;hs17:45212908-45213954,hs4:80273509-80274699;hs17:25263100-25269068,hs4:49639144-49659012;hs17:20778078-20784820,hs4:33857334-33864802;hs17:25263849-25268002,hs4:49107610-49122949;hs17:25263560-25266937,hs4:49147933-49157721;hs17:49974518-49979804,hs4:128965020-128965379;hs17:33478153-33478326,hs4:70296658-70296712;hs17:21508428-21515649,hs4:34006605-34009518;hs17:20771122-20777836,hs4:34006588-34010798;hs17:33478142-33478290,hs5:71146737-71146895;hs17:22252564-22261589,hs6:58773867-58779234;hs17:21520058-21547409,hs7:57641538-57669921;hs17:21511695-21518904,hs7:57633573-57645023;hs17:20768387-20784847,hs7:57625038-57645748;hs17:60606446-60626445,hs7:128224002-128245661;hs17:60536106-60545612,hs7:128155107-128158842;hs17:60524441-60526667,hs7:128138081-128145489;hs17:22249722-22262575,hs7:61984920-61992544;hs17:25263288-25269026,hs7:57545855-57558535;hs17:25291426-25302061,hs7:64958928-64969189;hs17:60554757-60560235,hs7:128167997-128178250;hs17:16096349-16098078,hs7:57658247-57663509;hs17:25292684-25300333,hs7:53229981-53237441;hs17:25265317-25274541,hs7:65055192-65059209;hs17:45213944-45216192,hs8:46947798-46948110;hs17:74559553-74562453,hs9:105963877-105970345;hs17:22249725-22262298,hsX:58561012-58564149;hs17:45212878-45219743,hsY:10020621-10031997;hs17:45232039-45235622,hsY:10025912-10032672;hs17:45247298-45249328,hsY:10026504-10027542;hs17:25263281-25269126,hsY:13445283-13459931;hs17:25263093-25267890,hsY:58972285-58982990;hs17:25264606-25269830,hsY:28784340-28809868;hs17:25263840-25267826,hsY:13841158-13862534;hs17:25263287-25268908,hsY:13136484-13142174;hs17:25264590-25267802,hsY:13194046-13196399;hs17:33478154-33478236,hsY:10036076-10036542;hs17:25266929-25269392,hsY:13648942-13654212;hs18:10608547-10624150,hs18:12210751-12227090;hs18:107004-110356,hs18:18511665-18520269;hs18:10628883-10637356,hs18:12190101-12201970;hs18:10602247-10608060,hs18:12230232-12233417;hs18:10909763-10917893,hs18:12077157-12084161;hs18:18511746-18520244,hs19:27750675-27759139;hs18:18512446-18520298,hs19:27731949-27744255;hs18:18511999-18520297,hs19:27760229-27769668;hs18:107503-109636,hs19:27731990-27740193;hs18:18511059-18520295,hs2:92270071-92299917;hs18:18511110-18520297,hs2:92300363-92325745;hs18:18511039-18520295,hs2:132996309-133005987;hs18:18512235-18519699,hs2:132981217-132988039;hs18:107048-111300,hs2:92304826-92309688;hs18:107005-110351,hs2:92288343-92300674;hs18:19792111-19792137,hs2:133025354-133030592;hs18:15098771-15107564,hs2:132638413-132647421;hs18:12897864-12897881,hs2:133026765-133030962;hs18:77086713-77086716,hs2:84320324-84320324;hs18:18511082-18520292,hs20:26292102-26319397;hs18:18512850-18520238,hs20:26260042-26270007;hs18:52711560-52712124,hs20:29646875-29648696;hs18:18512028-18520298,hs21:14365290-14368987;hs18:18512002-18520291,hs21:14340187-14350005;hs18:15050873-15063129,hs21:14679714-14688863;hs18:15072646-15078753,hs21:14663165-14674064;hs18:15080185-15089177,hs21:14650610-14664900;hs18:14700917-14711351,hs21:14817329-14826820;hs18:14718158-14729660,hs21:14801582-14814856;hs18:14142501-14159353,hs21:15370521-15391035;hs18:14861029-14878235,hs21:14734732-14753230;hs18:15059913-15062822,hs21:29389597-29395968;hs18:15063648-15067517,hs21:29385775-29389259;hs18:14620856-14631846,hs21:14897759-14912337;hs18:14177768-14189821,hs21:15344287-15354483;hs18:14130518-14138629,hs21:15391016-15398412;hs18:15072856-15078313,hs21:29375732-29376899;hs18:14545044-14553579,hs21:14974720-14978147;hs18:15306887-15314264,hs21:14426432-14433460;hs18:14660335-14670270,hs21:14857436-14867309;hs18:14861880-14868401,hs21:11097830-11105324;hs18:14435526-14443014,hs21:15083133-15093782;hs18:12121262-12127546,hs22:17153954-17163779;hs18:18517555-18520294,hs22:16850794-16861825;hs18:106816-111366,hs3:75718044-75718719;hs18:18511184-18520290,hs3:90365730-90370923;hs18:18513529-18520294,hs3:90456863-90478127;hs18:18511665-18520275,hs3:90486679-90498948;hs18:18513262-18520505,hs3:90401784-90414955;hs18:24548846-24556444,hs4:22621107-22623807;hs18:18512854-18519288,hs4:68264380-68266138;hs18:18511075-18520290,hs5:49531681-49548948;hs18:18511663-18520294,hs5:49510033-49517192;hs18:18511159-18520294,hs5:49437134-49441285;hs18:18516543-18520295,hs5:46355197-46369770;hs18:18513757-18520289,hs5:46397479-46404438;hs18:18510969-18520295,hs6:58773898-58779252;hs18:106881-111723,hs6:58773675-58779263;hs18:18512854-18520286,hs6:61893855-61918094;hs18:46956886-46956889,hs6:34768118-34768118;hs18:18511004-18520294,hs7:61078141-61090140;hs18:18511371-18520298,hs7:61967410-61989964;hs18:18511133-18520298,hs7:61990594-62006501;hs18:106989-111360,hs7:61967414-61975041;hs18:18512920-18520290,hs7:62020246-62029061;hs18:18512272-18520286,hs7:57994293-57999913;hs18:18512844-18520294,hs7:57985513-57986647;hs18:18516153-18520290,hs7:61535880-61551329;hs18:18511102-18520294,hs8:46839695-46857442;hs18:18512846-18520291,hs8:43817308-43831578;hs18:18511186-18520235,hs8:43770501-43786942;hs18:18511065-18520297,hs8:43790079-43794741;hs18:18512248-18520295,hs8:43092880-43096609;hs18:108387-111487,hs8:43092880-43096225;hs18:18516845-18519821,hs8:46901920-46909310;hs18:8922603-8928198,hs8:16708907-16714682;hs18:18511185-18520295,hs9:66820857-66836274;hs18:18511370-18520296,hs9:66800744-66803902;hs18:18512808-18520262,hs9:66796773-66798766;hs18:76434-83048,hs9:141034596-141039404;hs18:18511671-18520275,hs9:69964290-69964314;hs18:47349390-47352680,hs9:68351441-68360693;hs18:18512846-18519692,hs9:67317934-67320857;hs18:15402525-15407960,hs9:69957197-69958722;hs18:8820709-8820717,hs9:25973281-25973281;hs18:18511386-18523961,hsX:61820205-61849394;hs18:18511382-18520290,hsX:61745279-61759855;hs18:18512657-18520295,hsX:61730067-61736235;hs18:18511360-18520288,hsX:61760931-61769529;hs18:18511019-18520290,hsX:61810538-61819512;hs18:18511054-18520297,hsX:61871730-61875532;hs18:18510898-18520155,hsX:58546971-58563197;hs18:18516139-18520294,hsX:61913578-61916307;hs18:105823-112260,hsY:13460295-13489971;hs18:106821-111069,hsY:13490014-13490052;hs18:105666-112254,hsY:58978173-58999986;hs18:18511086-18520241,hsY:13460757-13469597;hs18:18511386-18522854,hsY:13483338-13486756;hs18:18511652-18519684,hsY:58976952-58999968;hs19:22112871-22129939,hs19:23114574-23127636;hs19:22106680-22114674,hs19:23102367-23107778;hs19:22573018-22589254,hs19:22833419-22848126;hs19:41320571-41332876,hs19:41624495-41636643;hs19:20750416-20761999,hs19:20946910-20958016;hs19:22517008-22524740,hs19:22906849-22914884;hs19:35027806-35036063,hs19:35230923-35239555;hs19:41315681-41321032,hs19:41639935-41645033;hs19:54881431-54889382,hs19:55000676-55007244;hs19:54870858-54875807,hs19:55015603-55021802;hs19:22202727-22218878,hs19:22414339-22432208;hs19:22528624-22538179,hs19:22895357-22904564;hs19:22183054-22188523,hs19:22390128-22391142;hs19:55244410-55251375,hs19:55353883-55365447;hs19:21816045-21823267,hs19:21949295-21953961;hs19:22484491-22485414,hs19:22950906-22957433;hs19:54787999-54791466,hs19:55133728-55138913;hs19:15761019-15764554,hs19:15993688-16002277;hs19:41394649-41402762,hs19:41563129-41569969;hs19:43320373-43322401,hs19:43486508-43492461;hs19:22101044-22107731,hs19:22317340-22318749;hs19:36804013-36809848,hs19:37751502-37756289;hs19:22207381-22217128,hs19:23194331-23204422;hs19:20079461-20084232,hs19:20757347-20760249;hs19:22383651-22388163,hs19:23173305-23177727;hs19:44860304-44889206,hs2:133080121-133108246;hs19:44884720-44889960,hs2:133075011-133079838;hs19:44890098-44899548,hs2:133070774-133079433;hs19:44855154-44859964,hs2:133104476-133109189;hs19:44896737-44906880,hs2:133062970-133070580;hs19:44956536-44964103,hs2:162135094-162138957;hs19:44910942-44920627,hs2:162134305-162138967;hs19:44912821-44919047,hs2:133040195-133045457;hs19:27731962-27739247,hs2:92275916-92297956;hs19:27788860-27789921,hs2:92306079-92309689;hs19:30777389-30777481,hs2:133022488-133030592;hs19:44957775-44964223,hs2:133040475-133052084;hs19:48893802-48893830,hs2:133026720-133031291;hs19:51001653-51005583,hs2:133022222-133030657;hs19:27731984-27738585,hs2:133026944-133034033;hs19:54922864-54923063,hs2:133022661-133030969;hs19:27732027-27740198,hs20:26311718-26319413;hs19:27835041-27845193,hs21:10698412-10704306;hs19:44915321-44918114,hs21:9696030-9699301;hs19:27732008-27738654,hs21:10719066-10730516;hs19:44958281-44963971,hs21:9827107-9835903;hs19:24183674-24184102,hs21:15457350-15457389;hs19:36066521-36066713,hs21:15457337-15457362;hs19:27731928-27740221,hs4:68264216-68267698;hs19:44959179-44963188,hs4:49512322-49517068;hs19:44915615-44919233,hs4:49323160-49326209;hs19:36066508-36066718,hs4:76807184-76807312;hs19:44914048-44918982,hs4:49512342-49516957;hs19:24184072-24184110,hs4:76807175-76807201;hs19:24526157-24526183,hs4:68264838-68266455;hs19:27731982-27739323,hs5:46336285-46346837;hs19:27732056-27740191,hs5:46392148-46395654;hs19:27731906-27751321,hs6:58773628-58779983;hs19:27755093-27759626,hs6:58773877-58779242;hs19:27760495-27769171,hs6:58774049-58779190;hs19:27731979-27738870,hs6:61906404-61914295;hs19:27790228-27793815,hs6:58776775-58779242;hs19:24569741-24571830,hs6:58774500-58779248;hs19:27821681-27828132,hs6:58776790-58779249;hs19:27731904-27744725,hs7:61967158-61988615;hs19:27732044-27740166,hs7:107406558-107410630;hs19:7305199-7306602,hs7:101330584-101331081;hs19:36066506-36066712,hs8:70602320-70602565;hs19:27732055-27739274,hs8:46850007-46861527;hs19:27732054-27739062,hs8:46868592-46869443;hs19:27732009-27741636,hs8:43092872-43096989;hs19:24184078-24184777,hs8:70602349-70602568;hs19:27731904-27738467,hs8:43792762-43798872;hs19:55777892-55777935,hs8:143265074-143268202;hs19:24183656-24184697,hs9:79186658-79186846;hs19:13250512-13253998,hs9:33286166-33291144;hs19:27732001-27740762,hsX:61727852-61735500;hs19:27731890-27740185,hsY:13460431-13486221;hs19:27732009-27740219,hsY:58985053-58997076;hs20:25903028-25929404,hs20:29450114-29479649;hs20:25927305-25938279,hs20:29477766-29488963;hs20:25894026-25902191,hs20:29440871-29452026;hs20:25941624-25949469,hs20:29488477-29498585;hs20:25880338-25894029,hs20:29430182-29443436;hs20:25870102-25876692,hs20:29420376-29425515;hs20:25876598-25881422,hs20:29426135-29431877;hs20:25735573-25745631,hs20:26073645-26079685;hs20:25856355-25864968,hs20:26248764-26255068;hs20:25754289-25759823,hs20:26054715-26061226;hs20:46503351-46506717,hs20:47137782-47141536;hs20:46520877-46526623,hs20:47128309-47135551;hs20:46603514-46608158,hs20:46994282-47002930;hs20:49254965-49261154,hs20:49382105-49388041;hs20:29440137-29449714,hs21:9413866-9418937;hs20:29422436-29436789,hs21:9423005-9436471;hs20:25875565-25890744,hs21:9423473-9436233;hs20:29804392-29817216,hs21:10827139-10839226;hs20:26188818-26190098,hs21:9826995-9827526;hs20:29822328-29829737,hs21:10812950-10822070;hs20:29803913-29818895,hs21:10799412-10803015;hs20:25891076-25903605,hs21:9411476-9418918;hs20:52219032-52220234,hs21:10989304-10996325;hs20:26230168-26237373,hs22:17230305-17236494;hs20:26248772-26256860,hs22:17232672-17241084;hs20:25856356-25862858,hs22:17235992-17241214;hs20:26197174-26214258,hs3:75982956-76003212;hs20:26220392-26223922,hs3:75982572-75986907;hs20:29617312-29637525,hs4:190870185-190884818;hs20:29580798-29605166,hs4:190820075-190846928;hs20:29632581-29641812,hs4:190891230-190896891;hs20:29610616-29622092,hs4:190860166-190869917;hs20:29600593-29609703,hs4:190852158-190859917;hs20:29610010-29612303,hs4:190857464-190859721;hs20:29607899-29609704,hs4:190860325-190862529;hs20:29646741-29653856,hs4:190197959-190205310;hs20:26138454-26149446,hs4:33834498-33850728;hs20:26122668-26135256,hs4:33853954-33863687;hs20:29812120-29822984,hs4:49105370-49117251;hs20:29804645-29829358,hs4:49636913-49649898;hs20:29811238-29829478,hs4:49149015-49155493;hs20:26286371-26289501,hs6:58773768-58779194;hs20:26260566-26281572,hs6:58773877-58779187;hs20:26302414-26319398,hs6:58773380-58779045;hs20:31274965-31280211,hs6:33539048-33545342;hs20:52021439-52021583,hs6:88214313-88220076;hs20:26126761-26148954,hs7:57603675-57627452;hs20:26122149-26127923,hs7:57629156-57636003;hs20:26100633-26109390,hs7:57643585-57657604;hs20:26238681-26252832,hs7:57725807-57738483;hs20:26233526-26237470,hs7:57713795-57721312;hs20:26083112-26097087,hs7:57655722-57670015;hs20:25826778-25836750,hs7:57698677-57709038;hs20:29428376-29435453,hs7:57744482-57754152;hs20:29420156-29426277,hs7:57733738-57743633;hs20:29451853-29459859,hs7:57767485-57776295;hs20:25862349-25868886,hs7:57725790-57734273;hs20:25869238-25884671,hs7:57735134-57747684;hs20:25903045-25909923,hs7:57768824-57777095;hs20:29480521-29488755,hs7:57797259-57803714;hs20:29651262-29653875,hs9:68422242-68425876;hs20:29630196-29638742,hs9:68420418-68434433;hs20:29617071-29629997,hs9:68428586-68449659;hs20:29610213-29621744,hs9:68450029-68459047;hs20:29606088-29609704,hs9:68454725-68459042;hs20:29580584-29608694,hs9:68460112-68489698;hs20:29611373-29622966,hs9:68728741-68735825;hs20:29501766-29509504,hs9:44890701-44893583;hs20:29487154-29494370,hs9:44900963-44908232;hs20:26297479-26319397,hs9:66833244-66837341;hs20:29616091-29623960,hs9:69069344-69074600;hs20:29580800-29592945,hs9:68691028-68705873;hs20:4080726-4085046,hs9:90372792-90374483;hs20:26258933-26261180,hsX:61728354-61734103;hs20:29807045-29828188,hsY:13812851-13827075;hs20:29812383-29820463,hsY:13865757-13869969;hs20:29828063-29832968,hsY:13855549-13869429;hs20:29812068-29823644,hsY:13855549-13862723;hs20:29827355-29832100,hsY:13453607-13458360;hs20:29822996-29833207,hsY:58971565-58980979;hs20:29813715-29824967,hsY:58827305-58827343;hs21:9854568-9867619,hs21:10611222-10623557;hs21:9832978-9841633,hs21:10641162-10643289;hs21:9990861-9995718,hs21:10136039-10141555;hs21:11097716-11103169,hs21:14741555-14748696;hs21:10942655-10945017,hs21:11177624-11180219;hs21:44959759-44965071,hs21:47022928-47024850;hs21:11144310-11169406,hs22:17493304-17518766;hs21:11170125-11172957,hs22:17515527-17518867;hs21:11178607-11188048,hs22:18875939-18891105;hs21:11106066-11117546,hs22:43428607-43435970;hs21:10895168-10907004,hs22:17119997-17129825;hs21:9490233-9519984,hs3:630846-659738;hs21:9520488-9529469,hs3:621560-635017;hs21:9530671-9539071,hs3:612337-624777;hs21:9490174-9495312,hs3:660074-663441;hs21:10003618-10012869,hs3:75870118-75880641;hs21:9996835-10000881,hs3:75860505-75868411;hs21:10134867-10146143,hs3:75854327-75862977;hs21:9938679-9947814,hs3:75799305-75810101;hs21:33807112-33810204,hs3:129800195-129805094;hs21:9695827-9700724,hs4:49512297-49518698;hs21:9696090-9700730,hs4:49300422-49326211;hs21:9646107-9668690,hs4:49160054-49184193;hs21:9646117-9647292,hs4:49159183-49159759;hs21:9695133-9699578,hs4:49290616-49292899;hs21:10780424-10789228,hs4:49105612-49112882;hs21:10795696-10809311,hs4:49643072-49659695;hs21:10833853-10845802,hs4:49146831-49152890;hs21:10850174-10858995,hs4:49146830-49156583;hs21:10366024-10375720,hs4:132624994-132638636;hs21:10811974-10829112,hs4:49142552-49153758;hs21:10800970-10809583,hs4:49151775-49156596;hs21:10780464-10795740,hs4:49145685-49154981;hs21:9663277-9666412,hs4:49619262-49623153;hs21:10543258-10566092,hs4:132844854-132866834;hs21:9645842-9650912,hs4:49628753-49633364;hs21:9715974-9720101,hs4:49262503-49264475;hs21:9826979-9830535,hs4:49512337-49517868;hs21:11097676-11109601,hs5:180700229-180711050;hs21:10702047-10709558,hs5:49540139-49548954;hs21:14340360-14368917,hs6:58774506-58779234;hs21:10743605-10758467,hs6:58773894-58779252;hs21:10700217-10714378,hs6:58776506-58778666;hs21:10780477-10795420,hs6:58776595-58779792;hs21:11050022-11079680,hs7:151960372-151989502;hs21:11040188-11049995,hs7:151953397-151965317;hs21:11074251-11096645,hs7:152073384-152092566;hs21:11031761-11042957,hs7:151940000-151948830;hs21:11093765-11096183,hs7:152098319-152099999;hs21:11095562-11097298,hs7:152100010-152101953;hs21:11022658-11036753,hs7:151930757-151939998;hs21:11118124-11119328,hs7:152076862-152077923;hs21:11097559-11098888,hs7:152109988-152113697;hs21:9419110-9428368,hs7:57752164-57759667;hs21:9426192-9436341,hs7:57741365-57749252;hs21:9411392-9412605,hs7:57767369-57768580;hs21:10740102-10758089,hs7:58016306-58021740;hs21:10995006-11007557,hs7:151900965-151912187;hs21:10785104-10798936,hs7:57547155-57556143;hs21:10763139-10766544,hs7:57990529-57998645;hs21:10754856-10762755,hs7:57945762-57951898;hs21:10741625-10749455,hs7:61968665-61969354;hs21:9893518-9901724,hs7:97491260-97498940;hs21:14742964-14744518,hs7:152109545-152112663;hs21:21846072-21854175,hs7:61968931-61969312;hs21:10643471-10647803,hs9:68341104-68343796;hs21:14338284-14341863,hs9:66821044-66825832;hs21:11114302-11139402,hsX:853199-875271;hs21:11140262-11145745,hsX:870812-878896;hs21:11113300-11119627,hsX:842438-843128;hs21:10700555-10707654,hsX:61892125-61899557;hs21:9890055-9919958,hsY:13292484-13319728;hs21:9915048-9929729,hsY:13319654-13329271;hs21:9885390-9888096,hsY:13290254-13294444;hs21:9926356-9929316,hsY:13330916-13334373;hs21:9825482-9830586,hsY:10031962-10037863;hs21:10000240-10022088,hsY:13403927-13423968;hs21:11054348-11057116,hsY:59001010-59003645;hs21:11054883-11057123,hsY:59027623-59029603;hs21:9862680-9888097,hsY:13240144-13265321;hs21:10780489-10809784,hsY:58970127-58983244;hs21:10780409-10809785,hsY:13445880-13459568;hs21:10774357-10778555,hsY:58978008-58985949;hs21:10773262-10779695,hsY:13446432-13459296;hs21:9948668-9963488,hsY:13349688-13362858;hs21:10791315-10812381,hsY:28784388-28791286;hs21:10698115-10704333,hsY:10041451-10044496;hs21:10774606-10797597,hsY:28797588-28801647;hs21:10776062-10789505,hsY:28784199-28791283;hs21:9980183-9986608,hsY:13380240-13390943;hs21:10794050-10802125,hsY:13859382-13869467;hs21:10804001-10812771,hsY:13803091-13815571;hs21:10798196-10802702,hsY:13815864-13824821;hs21:10812951-10826243,hsY:13804742-13812663;hs21:10710898-10726522,hsY:10054599-10069718;hs21:10816553-10821878,hsY:13857534-13869672;hs21:10809211-10827738,hsY:13845535-13855549;hs21:10841574-10851555,hsY:13831090-13842781;hs21:10849552-10858351,hsY:13445871-13460880;hs21:10815227-10827152,hsY:13655852-13665482;hs21:10085048-10088475,hsY:13443438-13458693;hs21:10799545-10809327,hsY:58855278-58856072;hs21:10909501-10921457,hsY:28708498-28720802;hs21:10138907-10140553,hsY:13391033-13393213;hs21:10129409-10139079,hsY:13398291-13404327;hs21:10773764-10785237,hsY:13137787-13143629;hs21:10085029-10087268,hsY:28784380-28788159;hs21:10085041-10089094,hsY:58976484-58984677;hs21:9480020-9487925,hsY:13632111-13640031;hs22:25651482-25669375,hs22:25900072-25924221;hs22:25681309-25696902,hs22:25980029-25990572;hs22:25695464-25698190,hs22:25999500-26004460;hs22:32696628-32705749,hs22:44636108-44642249;hs22:29792289-29807090,hs22:32549131-32559255;hs22:25700541-25701808,hs22:26000693-26002406;hs22:25635692-25644868,hs22:25863392-25867175;hs22:32680263-32690129,hs22:44622865-44631821;hs22:18874351-18888495,hs22:23825371-23830008;hs22:22309278-22311019,hs22:22573038-22574342;hs22:17186801-17194343,hs3:75962643-75974395;hs22:32927911-32928513,hs6:24681443-24686540;hs22:16849138-16861874,hs6:58776485-58779804;hs22:16848269-16862361,hs7:61780387-61802866;hs22:16847994-16862422,hs7:61738427-61757510;hs22:17229278-17238084,hs7:57713095-57722795;hs22:23781198-23798270,hs7:1862650-1875137;hs22:17239483-17241101,hs7:57725047-57729467;hs22:16856374-16862989,hs7:57546323-57556560;hs22:23771880-23774415,hs7:1915308-1918904;hs22:16861625-16861821,hs7:61969015-61970375;hs22:32574435-32577854,hs9:101476809-101480166;hs22:16942514-16955862,hsY:13527836-13539651;hsX:155030063-155035964,hsX:155214025-155216642;hsX:52886836-52894237,hsX:55676597-55684836;hsX:58560400-58563782,hsX:61713195-61725546;hsX:58561269-58561412,hsX:61839277-61839312;hsX:139087492-139103638,hsX:139297563-139309800;hsX:130809769-130813301,hsX:130971871-130977317;hsX:154871080-154871348,hsX:155184217-155190831;hsX:146048365-146055641,hsX:146265295-146268273;hsX:89525193-89541766,hsY:3708423-3729018;hsX:92240792-92255347,hsY:5971402-5986182;hsX:92110229-92119730,hsY:5840274-5849375;hsX:89130535-89141410,hsY:3396082-3409267;hsX:90937679-90947130,hsY:4788000-4800558;hsX:88901714-88909247,hsY:3174752-3183666;hsX:2696958-2699354,hsY:2649614-2651806;hsX:89193063-89203327,hsY:3466090-3471396;hsX:91565895-91572172,hsY:5295591-5297197;hsX:1259746-1260814,hsY:10019348-10026945;hsX:2831910-2834856,hsY:14491353-14493820;hsY:13460239-13489982,hsY:58975827-58999985;hsY:13450061-13459932,hsY:58974185-58983200;hsY:13490002-13490056,hsY:58983319-58998127;hsY:13445882-13449953,hsY:58973146-58985770;hsY:13650584-13662454,hsY:13830795-13859925;hsY:13675466-13681159,hsY:13833253-13849614;hsY:13685685-13689626,hsY:13842019-13857781;hsY:13677612-13693228,hsY:13851643-13869437;hsY:13677756-13688122,hsY:13813154-13826337;hsY:13448666-13459261,hsY:13841584-13869826;hsY:13859919-13869825,hsY:58969904-58976719;hsY:13843953-13855086,hsY:58972080-58982836;hsY:13830007-13842143,hsY:58972968-58980090;hsY:28578322-28585956,hsY:58967753-58974355;hsY:13800611-13822614,hsY:58971985-58979849;hsY:28784413-28791284,hsY:58976034-58982827;hsY:13137315-13143793,hsY:13446677-13460969;hsY:28798230-28801657,hsY:58972066-58982026;hsY:13444731-13458698,hsY:28784418-28801080;hsY:13675676-13687883,hsY:58972798-58979849;hsY:13137981-13143801,hsY:28784354-28793791;hsY:13136036-13143799,hsY:58972696-58982857;hsY:13446572-13454865,hsY:13680949-13687237;hsY:13661301-13661304,hsY:58827305-58827349;hsY:8964953-8967920,hsY:23896548-23899349;hsY:13462031-13464472,hsY:13476590-13478395;hsY:13476218-13476833,hsY:13478396-13482330;hsY:23211970-23212943,hsY:23225868-23226907;hsY:59010332-59011074,hsY:59025184-59025745;hsX:6134512-6134574,hsX:6137826-6138113;hsX:45545093-45545801,hsX:45550430-45550707;hsX:46807813-46810338,hsX:46828696-46829871;hsX:49010942-49012292,hsX:49018315-49018856;hsX:134747855-134749294,hsX:134806391-134809528;hsX:149568252-149568330,hsX:149584568-149585008;hs1:17000642-17005197,hs1:17056212-17056222;hs1:26965368-26965552,hs1:26972144-26973314;hs1:71846360-71849884,hs1:71850164-71850509;hs1:80792896-80794646,hs1:80794774-80797756;hs1:121484310-121484980,hs1:121485034-121485044;hs1:142726109-142726927,hs1:142815860-142817141;hs1:142728948-142729084,hs1:142808182-142808913;hs1:143278360-143279040,hs1:143283617-143283746;hs1:153373107-153374071,hs1:153438944-153440028;hs1:153388175-153388241,hs1:153431773-153436336;hs1:175197878-175198443,hs1:175201868-175201880;hs1:187461777-187462380,hs1:187466548-187466646;hs1:197754467-197757794,hs1:197757923-197758850;hs1:205813133-205814452,hs1:205823076-205823993;hs1:227679309-227680722,hs1:227693434-227695231;hs1:227684982-227688791,hs1:227689348-227690467;hs1:247287868-247291174,hs1:247336560-247337480;hs1:247291089-247291436,hs1:247331098-247331241;hs1:248643924-248645788,hs1:248726696-248728414;hs2:50814092-50814216,hs2:50814429-50818988;hs2:61698653-61703062,hs2:61703200-61703226;hs2:85544072-85546105,hs2:85570227-85571880;hs2:89831774-89832556,hs2:89845689-89846044;hs2:89865237-89868993,hs2:89877848-89878355;hs2:125049116-125049775,hs2:125053053-125053208;hs2:132517652-132518510,hs2:132556422-132556787;hs2:133021983-133023559,hs2:133027342-133027347;hs2:133027997-133028630,hs2:133028632-133030599;hs2:139002336-139003683,hs2:139007563-139008447;hs2:241613249-241613587,hs2:241642282-241642898;hs3:28396802-28396812,hs3:28404727-28404903;hs3:44738590-44741492,hs3:44741845-44743920;hs3:128346689-128347227,hs3:128375405-128375954;hs3:148476654-148477106,hs3:148499263-148499387;hs3:151603715-151606462,hs3:151615984-151618062;hs4:40232731-40234716,hs4:40235057-40236401;hs4:49289623-49291295,hs4:49325154-49326203;hs4:49303129-49304045,hs4:49323760-49325157;hs4:70083744-70084455,hs4:70139548-70139889;hs4:70179354-70179374,hs4:70203216-70208161;hs4:88846500-88847823,hs4:88856966-88860237;hs4:165834149-165837927,hs4:165891562-165892196;hs4:188868331-188869065,hs4:188875318-188875786;hs4:190582612-190584784,hs4:190611705-190612889;hs5:4793591-4793596,hs5:4796816-4797178;hs5:178872524-178872815,hs5:178929388-178929624;hs6:12429017-12429685,hs6:12432113-12432608;hs6:20187034-20187842,hs6:20190534-20190752;hs6:31009416-31009481,hs6:31011275-31011622;hs6:58773881-58776933,hs6:58777718-58777838;hs6:89920590-89923823,hs6:89923764-89925449;hs6:94737698-94739073,hs6:94741154-94741176;hs6:107166085-107169412,hs6:107171444-107172580;hs6:157556701-157557611,hs6:157641063-157641200;hs6:157609533-157609636,hs6:157691998-157692336;hs6:167625329-167629465,hs6:167725258-167725603;hs6:167630909-167630976,hs6:167700908-167701300;hs6:167636749-167638315,hs6:167697727-167697777;hs6:167647503-167647795,hs6:167687112-167687714;hs6:169090329-169090560,hs6:169094335-169094587;hs6:170426898-170429280,hs6:170429247-170431109;hs7:48891112-48893769,hs7:48955823-48957742;hs7:48902655-48903145,hs7:48945516-48945803;hs7:61739758-61743925,hs7:61803681-61804277;hs7:61967377-61969436,hs7:61969042-61971068;hs7:70418293-70420445,hs7:70437123-70438142;hs7:70426191-70427383,hs7:70440481-70441060;hs7:75456338-75458035,hs7:75463764-75466883;hs7:107056503-107057512,hs7:107062555-107062751;hs7:158923322-158925205,hs7:158954039-158956572;hs8:6152635-6154134,hs8:6155861-6157243;hs8:43092853-43092863,hs8:43094945-43098771;hs8:48212283-48214937,hs8:48230705-48232474;hs9:66459028-66461277,hs9:66472083-66474093;hs9:66469943-66472047,hs9:66478991-66481385;hs9:68418968-68421228,hs9:68424156-68426582;hs9:76896705-76897318,hs9:76898203-76898216;hs9:94889885-94890216,hs9:94961942-94966321;hs10:4971177-4971905,hs10:5067563-5067889;hs10:4980564-4982155,hs10:5061729-5063724;hs10:4994350-4994703,hs10:5058428-5058637;hs10:4996124-4997869,hs10:5050733-5053013;hs10:5004669-5004681,hs10:5044486-5044711;hs10:5010048-5011479,hs10:5037958-5038787;hs10:37390766-37391091,hs10:37400141-37400262;hs10:39077891-39078815,hs10:39143366-39143490;hs10:39085244-39088266,hs10:39141388-39142448;hs10:39090890-39094173,hs10:39128338-39129096;hs10:39092867-39094175,hs10:39149079-39149080;hs10:39105141-39108696,hs10:39134352-39135690;hs10:39107542-39108706,hs10:39144911-39146073;hs10:42384698-42385531,hs10:42396959-42399493;hs10:47020314-47023035,hs10:47057346-47058816;hs10:81315745-81316878,hs10:81371578-81372419;hs10:81321486-81321610,hs10:81371581-81371602;hs10:127190429-127190595,hs10:127193889-127195153;hs10:127591144-127594125,hs10:127607704-127608047;hs11:305111-305852,hs11:320557-321089;hs11:311521-311971,hs11:319830-320780;hs11:1915318-1917492,hs11:1961164-1962317;hs11:1934915-1935931,hs11:1960520-1960556;hs11:4245556-4250217,hs11:4270366-4270374;hs11:18264843-18267446,hs11:18290934-18293109;hs11:36328855-36331504,hs11:36331508-36332741;hs11:55361862-55363650,hs11:55432839-55434332;hs11:55444035-55444697,hs11:55459414-55460362;hs11:57968440-57971100,hs11:57980562-57982827;hs11:59973548-59974358,hs11:60072661-60073230;hs11:61859600-61859730,hs11:61868044-61868084;hs11:99687945-99691042,hs11:99691087-99691458;hs11:117002385-117003349,hs11:117080405-117080681;hs12:60243-60966,hs12:156482-157731;hs12:9469911-9470159,hs12:9568185-9569726;hs12:12542382-12543200,hs12:12545228-12546555;hs12:30405703-30405942,hs12:30494966-30495106;hs12:71531730-71532800,hs12:71533024-71536042;hs12:87240209-87241675,hs12:87254112-87255304;hs12:124922336-124923625,hs12:124923378-124925267;hs13:37886465-37887372,hs13:37891807-37891825;hs14:65286677-65289016,hs14:65289026-65291149;hs16:1276051-1277524,hs16:1295424-1297019;hs16:20490685-20490714,hs16:20553146-20553147;hs16:20496126-20497060,hs16:20547189-20548174;hs16:33864665-33866600,hs16:33902114-33902215;hs16:33915759-33915884,hs16:33984083-33986594;hs16:46385804-46387657,hs16:46425489-46427693;hs16:46385819-46387386,hs16:46416937-46417011;hs16:46385909-46388894,hs16:46442305-46444149;hs16:46385984-46390935,hs16:46450289-46450303;hs16:46386014-46387929,hs16:46433033-46435047;hs16:46391768-46392217,hs16:46418127-46418378;hs16:46391781-46395014,hs16:46425689-46425902;hs16:46391979-46392020,hs16:46435501-46435531;hs16:46394324-46395390,hs16:46455014-46455245;hs16:46397928-46398836,hs16:46432732-46434384;hs16:46397997-46399820,hs16:46420102-46420542;hs16:46398763-46398771,hs16:46427315-46427495;hs16:46398773-46398840,hs16:46438782-46441368;hs16:46398883-46401797,hs16:46497667-46499063;hs16:46400008-46403006,hs16:46448017-46448366;hs16:46401607-46403742,hs16:46453534-46454232;hs16:46403656-46405139,hs16:46433649-46435045;hs16:46403812-46403816,hs16:46426012-46427551;hs16:46404467-46404953,hs16:46417278-46420773;hs16:46405005-46407695,hs16:46442326-46444130;hs16:46407677-46407694,hs16:46450311-46454314;hs16:46409061-46412259,hs16:46427472-46427586;hs16:46410354-46412249,hs16:46419481-46420035;hs16:46411435-46411475,hs16:46432581-46432738;hs16:55764701-55765039,hs16:55853379-55853404;hs16:55790440-55793323,hs16:55868508-55870601;hs16:55794008-55795736,hs16:55863336-55864417;hs16:55800133-55801874,hs16:55857523-55858531;hs16:55806241-55806712,hs16:55857290-55857689;hs16:55810847-55811019,hs16:55850844-55850863;hs16:75237785-75237855,hs16:75256058-75256136;hs16:85186134-85186736,hs16:85189077-85189295;hs17:5883184-5886596,hs17:5886647-5888215;hs17:21252947-21253384,hs17:21352582-21352583;hs17:26154273-26154618,hs17:26166971-26166985;hs17:36348958-36349650,hs17:36404555-36404805;hs17:41381304-41382321,hs17:41400869-41401129;hs17:41381709-41381953,hs17:41466272-41466401;hs17:41399193-41400375,hs17:41463616-41466465;hs17:58110951-58112140,hs17:58186130-58187373;hs18:18511039-18513027,hs18:18518120-18518136;hs18:18517045-18517706,hs18:18518708-18518942;hs19:20798560-20799428,hs19:20883559-20883659;hs19:20803995-20804001,hs19:20883364-20883466;hs19:21824876-21826982,hs19:21921211-21922129;hs19:21831980-21834236,hs19:21917293-21919924;hs19:27732000-27732214,hs19:27736481-27738464;hs19:39259395-39259886,hs19:39280923-39282021;hs19:44890031-44890490,hs19:44975023-44975188;hs19:44896833-44899578,hs19:44967504-44968976;hs19:44913623-44915625,hs19:44961191-44963036;hs19:53782093-53783445,hs19:53804490-53805437;hs19:58343619-58344421,hs19:58392299-58396019;hs20:26208358-26208629,hs20:26211024-26211039;hs20:46461385-46463003,hs20:46523679-46524585;hs20:57911727-57913861,hs20:57931821-57933832;hs21:9695525-9696137,hs21:9699568-9699597;hs21:27371336-27371930,hs21:27374266-27374291;hs21:28018734-28021176,hs21:28020929-28023315;hs21:46008137-46013052,hs21:46058464-46058495;hs22:36624549-36628178,hs22:36658216-36658591 Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands A variety of mutational mechanisms shape the dynamic architecture of human genomes and occasionally result in congenital defects and disease. Here, we used genome-wide long mate-pair sequencing to systematically screen for inherited and de novo structural variation in a trio including a child with severe congenital abnormalities. We identified 4321 inherited structural variants and 17 de novo rearrangements. We characterized the de novo structural changes to the base-pair level revealing a complex series of balanced inter- and intra-chromosomal rearrangements consisting of 12 breakpoints involving chromosomes 1, 4 and 10. Detailed inspection of breakpoint regions indicated that a series of simultaneous double-stranded DNA breaks caused local shattering of chromosomes. Fusion of the resulting chromosomal fragments involved non-homologous end joining, since junction points displayed limited or no homology and small insertions and deletions. The pattern of random joining of chromosomal fragments that we observe here strongly resembles the somatic rearrangement patterns--termed chromothripsis--that have recently been described in deranged cancer cells. We conclude that a similar mechanism may also drive the formation of de novo structural variation in the germline. GRCh37/hg19 NA CTDB0238 Research 22553170 Lapuk AV, Wu C, Wyatt AW, McPherson A, McConeghy BJ, Brahmbhatt S, Mo F, Zoubeidi A, Anderson S, Bell RH, Haegert A, Shukin R, Wang Y, Fazli L, Hurtado-Coll A, Jones EC, Hach F, Hormozdiari F, Hajirasouliha I, Boutros PC, Bristow RG, Zhao Y, Marra MA, Fanjul A, Maher CA, Chinnaiyan AM, Rubin MA, Beltran H, Sahinalp SC, Gleave ME, Volik SV, Collins CC From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer Journal of Pathology 2012 Jul 2,9 Prostate cancer Next Generation Sequencing Homo sapiens 890 Illumina GA-IIx FUBP1;ETV1;DENND1A;ANXA4;ANXA4;TMEM67;ABL1;ANXA4;ABL1;ANXA4;RALGPS1;EXOC6B;GPR107;C2orf28;MAP3K5;TCF12;ZNF638;KCNS3;PPM1G;SLC35D2;LPPR1;MRPL50;DTNB;SPTLC1;TMEM55A;LCLAT1;ABL1;ANXA4 Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada The current paradigm of cancer care relies on predictive nomograms which integrate detailed histopathology with clinical data. However, when predictions fail, the consequences for patients are often catastrophic, especially in prostate cancer where nomograms influence the decision to therapeutically intervene. We hypothesized that the high dimensional data afforded by massively parallel sequencing (MPS) is not only capable of providing biological insights, but may aid molecular pathology of prostate tumours. We assembled a cohort of six patients with high-risk disease, and performed deep RNA and shallow DNA sequencing in primary tumours and matched metastases where available. Our analysis identified copy number abnormalities, accurately profiled gene expression levels, and detected both differential splicing and expressed fusion genes. We revealed occult and potentially dormant metastases, unambiguously supporting the patients' clinical history, and implicated the REST transcriptional complex in the development of neuroendocrine prostate cancer, validating this finding in a large independent cohort. We massively expand on the number of novel fusion genes described in prostate cancer; provide fresh evidence for the growing link between fusion gene aetiology and gene expression profiles; and show the utility of fusion genes for molecular pathology. Finally, we identified chromothripsis in a patient with chronic prostatitis. Our results provide a strong foundation for further development of MPS-based molecular pathology. NCBI 36/hg18 Yes ADAMTS12,PXDNL;CPLX2,UBXD8;EBF1,FBXL17;EBF1,FEM1C;EFNA5,PCDHB7;JMY,DMGDH;KCNN2,EBF1;LMAN2,AP3S1;NDUFAF2,MAST4;PDE4D,C5orf47;PDE4D,FAM172A;PDE4D,PPP2R2B;PDE8B,UIMC1;PPP2R2B,FAM172A;RASGRF2,RNF145;TRIM40,FBXO38;YTHDC2,PPP2R2B;ZFP62,RGNEF CTDB0240 Research 22367537 Jan J. Molenaar, JanKoster, Danny A. Zwijnenburg, Peter van Sluis, Linda J. Valentijn, Ida van der Ploeg, Mohamed Hamdi, Johan van Nes, Bart A. Westerman, Jennemiek van Arkel, Marli E. Ebus, Franciska Haneveld, Arjan Lakeman, Linda Schild, Piet Molenaar, Peter Stroeken, Max M. van Noesel, Ingrid Øra,, Evan E. Santo, Huib N. Caron, Ellen M. Westerhout, Rogier Versteeg Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes Nature 2012 Mar 5 Neuroblastoma Next Generation Sequencing Homo sapiens N492TL Complete Genomics hs5:505880-505880,hs5:141253644-141253644;hs5:2421826-2421826,hs5:146308075-146308075;hs5:4760501-4760501,hs5:39019225-39019225;hs5:6137111-6137111,hs5:90083731-90083731;hs5:9324431-9324431,hs5:41655885-41655885;hs5:9348873-9348873,hs5:114934028-114934028;hs5:11760417-11760417,hs5:27977696-27977696;hs5:13740640-13740640,hs5:59051499-59051499;hs5:15207741-15207741,hs5:41831767-41831767;hs5:15339020-15339020,hs5:41383777-41383777;hs5:19602595-19602595,hs5:28426332-28426332;hs5:20521548-20521548,hs5:169638752-169638752;hs5:24418024-24418024,hs5:109984353-109984353;hs5:26262890-26262890,hs5:50161614-50161614;hs5:27389679-27389679,hs5:132703955-132703955;hs5:27535183-27535183,hs5:33692907-33692907;hs5:28873420-28873420,hs5:178557781-178557781;hs5:28924692-28924692,hs5:122291307-122291307;hs5:30589928-30589928,hs5:178667344-178667344;hs5:30770897-30770897,hs5:53518132-53518132;hs5:33011850-33011850,hs5:139625724-139625724;hs5:36788007-36788007,hs5:149500684-149500684;hs5:36797381-36797381,hs5:109207907-109207907;hs5:37140742-37140742,hs5:60973020-60973020;hs5:38571443-38571443,hs5:68203915-68203915;hs5:41418732-41418732,hs5:148933418-148933418;hs5:41541102-41541102,hs5:125328732-125328732;hs5:43639564-43639564,hs5:158490933-158490933;hs5:44373067-44373067,hs5:71098824-71098824;hs5:45055480-45055480,hs5:177848295-177848295;hs5:45057254-45057254,hs5:112392319-112392319;hs5:50407386-50407386,hs5:78154960-78154960;hs5:53863615-53863615,hs5:76256564-76256564;hs5:57512095-57512095,hs5:148720678-148720678;hs5:61516365-61516365,hs5:138483460-138483460;hs5:70843575-70843575,hs5:109781889-109781889;hs5:78635147-78635147,hs5:169531256-169531256;hs5:90575199-90575199,hs5:142383814-142383814;hs5:91243045-91243045,hs5:93940836-93940836;hs5:91441785-91441785,hs5:110077083-110077083;hs5:95075493-95075493,hs5:126417393-126417393;hs5:95261550-95261550,hs5:141060222-141060222;hs5:98600449-98600449,hs5:177811525-177811525;hs5:99956677-99956677,hs5:135239174-135239174;hs5:101858877-101858877,hs5:160932164-160932164;hs5:103192066-103192066,hs5:177979903-177979903;hs5:113236269-113236269,hs5:178642678-178642678;hs5:116457059-116457059,hs5:171255958-171255958;hs5:119534979-119534979,hs5:131370638-131370638;hs5:125289905-125289905,hs5:150102063-150102063;hs5:130324660-130324660,hs5:167149479-167149479;hs5:132176217-132176217,hs5:158096347-158096347;hs5:132196513-132196513,hs5:167151738-167151738;hs5:132251922-132251922,hs5:140616096-140616096;hs5:132493349-132493349,hs5:132591487-132591487;hs5:134154919-134154919,hs5:173159070-173159070;hs5:140463799-140463799,hs5:142297549-142297549;hs5:144833647-144833647,hs5:150825682-150825682;hs5:146526208-146526208,hs5:167029541-167029541;hs5:164298340-164298340,hs5:167285101-167285101;hs5:164573095-164573095,hs5:167787947-167787947;hs5:165603857-165603857,hs5:171465871-171465871;hs5:170958662-170958662,hs5:171713363-171713363;hs5:177851040-177851040,hs5:180195641-180195641;hs3:178233865-178233865,hs3:178332685-178332685;hs5:11541345-11541345,hs5:11755381-11755381;hs6:5445744-5445744,hs6:5671590-5671590;hs14:44715816-44715816,hs14:44734659-44734659;hs16:3753627-3753627,hs16:3762464-3762464;hs17:54050349-54050349,hs17:54057465-54057465;hs4:129405538-129405538,hs4:129422086-129422086;hs6:13176292-13176292,hs6:13397191-13397191;hs1:48974695-48974695,hs1:49515675-49515675;hs5:49506125-49506125,hs5:50224586-50224586;hs5:70902060-70902060,hs5:71433225-71433225;hs6:135771909-135771909,hs6:136018407-136018407;hs5:11473966-11473966,hs5:41777864-41777864;hs5:11542809-11542809,hs5:35839131-35839131;hs5:33894406-33894406,hs5:93855734-93855734;hs5:34878110-34878110,hs5:156313530-156313530;hs5:38579619-38579619,hs5:126735475-126735475;hs5:39168312-39168312,hs5:94103833-94103833;hs5:41005814-41005814,hs5:159577401-159577401;hs5:41853139-41853139,hs5:146102139-146102139;hs5:53251364-53251364,hs5:156451003-156451003;hs5:59086727-59086727,hs5:156307553-156307553;hs5:71683647-71683647,hs5:132253793-132253793;hs5:72382145-72382145,hs5:167028264-167028264;hs5:83558368-83558368,hs5:121731381-121731381;hs5:90267221-90267221,hs5:178551397-178551397;hs5:90267793-90267793,hs5:178511862-178511862;hs5:96144197-96144197,hs5:141473898-141473898;hs5:108753408-108753408,hs5:143519149-143519149;hs5:108755217-108755217,hs5:178235334-178235334;hs5:109210284-109210284,hs5:170600741-170600741;hs5:112340955-112340955,hs5:132923989-132923989;hs5:120006212-120006212,hs5:159577091-159577091;hs5:121735139-121735139,hs5:130964530-130964530;hs5:124102723-124102723,hs5:145361285-145361285;hs5:128885117-128885117,hs5:175902268-175902268;hs5:132909120-132909120,hs5:171459992-171459992;hs5:140170777-140170777,hs5:167788756-167788756;hs5:142409706-142409706,hs5:178669991-178669991;hs8:4692429-4692429,hs8:24356666-24356666 ARHGAP26;CTNNBL1;FOXF1;KCNH4;NAALADL1;PLAC8L1;SETD4;STAT1;ZNF8 Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours. NCBI 36/hg18 EGAS00001000222 Yes ADAMTS12,C5orf36;ADAMTS19,CDHR2;ARHGAP26,ADAMTS2;ARL15,HAVCR2;C7,FABP6;CTNND2,OXCT1;CTNND2,SPEF2;DCP2,FSTL4;EDIL3,SNCAIP;ERAP1,NDFIP1;FCHO2,ODZ2;FSTL4,STK10;FYB,MCTP1;GPR98,ADAMTS2;LIFR,MEGF10;MAN2A1,RANBP17;MIR548C,RANBP17;OXCT1,PPP2R2B;PCDHA1,WWC1;PCDHA2,WWC1;PCDHA3,WWC1;PCDHA4,WWC1;PDE4D,TIMD4;PJA2,YIPF5;PJA2,ZNF354B;PRR16,FABP6;PTCD2,AFF4;SNCAIP,RAPGEF6;TTC23L,TIMD4;ZNF608,SH3RF2 CTDB0241 Research 22367537 Jan J. Molenaar, JanKoster, Danny A. Zwijnenburg, Peter van Sluis, Linda J. Valentijn, Ida van der Ploeg, Mohamed Hamdi, Johan van Nes, Bart A. Westerman, Jennemiek van Arkel, Marli E. Ebus, Franciska Haneveld, Arjan Lakeman, Linda Schild, Piet Molenaar, Peter Stroeken, Max M. van Noesel, Ingrid Øra,, Evan E. Santo, Huib N. Caron, Ellen M. Westerhout, Rogier Versteeg Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes Nature 2012 Mar 2 Neuroblastoma Next Generation Sequencing Homo sapiens N538TL Complete Genomics hs2:1629495-1629495,hs2:4971716-4971716;hs2:19125378-19125378,hs2:215040847-215040847;hs2:20655605-20655605,hs2:44666705-44666705;hs2:25439850-25439850,hs2:199935988-199935988;hs2:30619023-30619023,hs2:31660629-31660629;hs2:40222494-40222494,hs2:202705596-202705596;hs2:41367311-41367311,hs2:212743852-212743852;hs2:42011658-42011658,hs2:216844557-216844557;hs2:188967801-188967801,hs2:194767753-194767753;hs2:202353096-202353096,hs2:204977981-204977981;hs5:1578270-1578270,hs5:39064700-39064700;hs2:212480998-212480998,hs2:212952292-212952292;hs2:15898276-15898276,hs2:16271009-16271009;hs2:15930080-15930080,hs2:16269291-16269291;hs2:15948577-15948577,hs2:16234802-16234802;hs5:38883315-38883315,hs5:39066367-39066367;hs2:1105044-1105044,hs2:31199750-31199750;hs2:31322993-31322993,hs2:33324081-33324081;hs2:39780932-39780932,hs2:215671609-215671609;hs2:44821923-44821923,hs13:42812212-42812212;hs2:47489141-47489141,hs2:198007444-198007444;hs2:49227921-49227921,hs2:190028718-190028718;hs2:203104371-203104371,hs2:212078773-212078773 CRIM1;OR4P4;POGLUT1;TMC3 Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours. NCBI 36/hg18 EGAS00001000222 Yes BMPR2,ERBB4;C2orf34,ENOX1;EHD3,LTBP1;FSHR,WDR75;MSH2,SF3B1;SNTG2,GALNT14;TMEM178,ABCA12 CTDB0242 Research 22367537 Jan J. Molenaar, JanKoster, Danny A. Zwijnenburg, Peter van Sluis, Linda J. Valentijn, Ida van der Ploeg, Mohamed Hamdi, Johan van Nes, Bart A. Westerman, Jennemiek van Arkel, Marli E. Ebus, Franciska Haneveld, Arjan Lakeman, Linda Schild, Piet Molenaar, Peter Stroeken, Max M. van Noesel, Ingrid Øra,, Evan E. Santo, Huib N. Caron, Ellen M. Westerhout, Rogier Versteeg Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes Nature 2012 Mar 6 Neuroblastoma Next Generation Sequencing Homo sapiens N407TL Complete Genomics hs6:38539704-38539704,hs6:108711967-108711967;hs6:41708159-41708159,hs6:45087656-45087656;hs6:127711927-127711927,hs6:131526385-131526385;hs2:196497954-196497954,hs2:196505613-196505613;hs6:39449778-39449778,hs6:39485401-39485401;hs6:131528411-131528411,hs6:131546204-131546204;hs22:30280946-30280946,hs22:30286044-30286044;hsX:122562539-122562539,hsX:122574195-122574195;hs6:18213646-18213646,hs6:18565726-18565726;hs6:43115746-43115746,hs6:43509863-43509863;hs13:101516808-101516808,hs17:28722554-28722554;hs13:101523938-101523938,hs17:28722549-28722549 FCGR2A;MIIP;MUC16;OR10Q1;ZFAT Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours. NCBI 36/hg18 EGAS00001000222 Yes NA CTDB0243 Research 22367537 Jan J. Molenaar, JanKoster, Danny A. Zwijnenburg, Peter van Sluis, Linda J. Valentijn, Ida van der Ploeg, Mohamed Hamdi, Johan van Nes, Bart A. Westerman, Jennemiek van Arkel, Marli E. Ebus, Franciska Haneveld, Arjan Lakeman, Linda Schild, Piet Molenaar, Peter Stroeken, Max M. van Noesel, Ingrid Øra,, Evan E. Santo, Huib N. Caron, Ellen M. Westerhout, Rogier Versteeg Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes Nature 2012 Mar 5 Neuroblastoma Next Generation Sequencing Homo sapiens N753TL Complete Genomics hs1:43550391-43550391,hs1:161137536-161137536;hs5:14255630-14255630,hs5:17856351-17856351;hs5:60039862-60039862,hs5:141362204-141362204;hs5:126099096-126099096,hs5:134753058-134753058;hs5:136472159-136472159,hs5:137940753-137940753;hs5:145341640-145341640,hs5:145361236-145361236;hs10:70729772-70729772,hs10:70737811-70737811;hs11:44895990-44895990,hs11:44896817-44896817;hs12:40841359-40841359,hs12:40841865-40841865;hs9:27421249-27421249,hs9:27972515-27972515;hs5:14256356-14256356,hs5:132193461-132193461;hs9:27421249-27421249,hs9:27972515-27972515;hs11:70865620-70865620,hs17:35675500-35675500 ADAM30;BOD1L;KIF26A;KRTAP3-1;NOTCH4;PLUNC Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours. NCBI 36/hg18 EGAS00001000222 Yes TRIO,SHROOM1 CTDB0244 Research 22367537 Jan J. Molenaar, JanKoster, Danny A. Zwijnenburg, Peter van Sluis, Linda J. Valentijn, Ida van der Ploeg, Mohamed Hamdi, Johan van Nes, Bart A. Westerman, Jennemiek van Arkel, Marli E. Ebus, Franciska Haneveld, Arjan Lakeman, Linda Schild, Piet Molenaar, Peter Stroeken, Max M. van Noesel, Ingrid Øra,, Evan E. Santo, Huib N. Caron, Ellen M. Westerhout, Rogier Versteeg Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes Nature 2012 Mar 7 Neuroblastoma Next Generation Sequencing Homo sapiens N576TL Complete Genomics hs7:131301886-131301886,hs7:137807517-137807517;hs7:138568124-138568124,hs7:144486452-144486452;hs4:140860021-140860021,hs4:140867894-140867894;hs7:158389517-158389517,hs7:158393750-158393750;hs20:29501539-29501539,hs20:29516663-29516663;hs7:130203199-130203199,hs7:130273577-130273577;hs19:47272759-47272759,hs19:47387875-47387875;hs2:1078827-1078827,hs7:141014176-141014176;hs7:120491640-120491640,hs7:122005096-122005096;hs7:134395002-134395002,hs7:153549143-153549143 FAN1;OR10P1;PLD2;RASL11B Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours. NCBI 36/hg18 EGAS00001000222 Yes AGBL3,DPP6;C7orf58,CADPS2 CTDB0245 Research 22367537 Jan J. Molenaar, JanKoster, Danny A. Zwijnenburg, Peter van Sluis, Linda J. Valentijn, Ida van der Ploeg, Mohamed Hamdi, Johan van Nes, Bart A. Westerman, Jennemiek van Arkel, Marli E. Ebus, Franciska Haneveld, Arjan Lakeman, Linda Schild, Piet Molenaar, Peter Stroeken, Max M. van Noesel, Ingrid Øra,, Evan E. Santo, Huib N. Caron, Ellen M. Westerhout, Rogier Versteeg Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes Nature 2012 Mar 5 Neuroblastoma Next Generation Sequencing Homo sapiens N752TL Complete Genomics hs5:1302619-1302619,hs5:60127804-60127804;hs5:1349452-1349452,hs5:59877248-59877248;hs5:1365627-1365627,hs5:1474540-1474540;hs5:1378862-1378862,hs5:60032833-60032833;hs5:1491572-1491572,hs5:59886460-59886460;hs5:1524079-1524079,hs5:61340494-61340494;hs5:59538740-59538740,hs5:61369479-61369479;hs5:59801960-59801960,hs5:61323633-61323633 BRD7;CCDC108;CGNL1;DICER1;DOPEY2;MS4A4A;ORAI2;RGS5;SORCS3;TRAPPC6A;UBE4A;ZNF133 Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours. NCBI 36/hg18 EGAS00001000222 Yes NA CTDB0246 Research 22367537 Jan J. Molenaar, JanKoster, Danny A. Zwijnenburg, Peter van Sluis, Linda J. Valentijn, Ida van der Ploeg, Mohamed Hamdi, Johan van Nes, Bart A. Westerman, Jennemiek van Arkel, Marli E. Ebus, Franciska Haneveld, Arjan Lakeman, Linda Schild, Piet Molenaar, Peter Stroeken, Max M. van Noesel, Ingrid Øra,, Evan E. Santo, Huib N. Caron, Ellen M. Westerhout, Rogier Versteeg Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes Nature 2012 Mar 2 Neuroblastoma Next Generation Sequencing Homo sapiens N608TL Complete Genomics hs2:2550381-2550381,hs2:3431067-3431067;hs2:2639213-2639213,hs2:10383039-10383039;hs2:6542796-6542796,hs2:10257701-10257701;hs2:6947668-6947668,hs2:67119025-67119025;hs2:3176129-3176129,hs2:3179801-3179801;hs18:22361089-22361089,hs18:22384304-22384304;hs1:2449506-2449506,hs1:2450345-2450345;hs2:5730602-5730602,hs2:5892139-5892139;hs2:15872213-15872213,hs2:16299993-16299993;hs2:15945514-15945514,hs2:16227645-16227645;hs2:15980651-15980651,hs2:16167752-16167752;hs2:9954405-9954405,hs2:10361304-10361304;hs16:49140173-49140173,hs16:55776951-55776951 ACCN2;ACTR8;ADAMTS14;AKAP9;ALG13;ATP5J2;PTCD1;BUD31;PTCD1;C11ORF57;CACNB3;CEP350;CMAS;CSNK1G3;DARC;DDX55;DKK2;EHF;FAM102B;GPATCH4;IGSF22;LPIN1;MARK2;NAA25;NCKAP5;NQO1;OR51D1;PHC2;PIKFYVE;RIN2;RORC;RPS4X;Sep-09;SH3D19;SIX6;SRCRB4D;STK17A;TNPO2 Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours. NCBI 36/hg18 EGAS00001000222 Yes TAF1B,HPCAL1 CTDB0247 Research 22367537 Jan J. Molenaar, JanKoster, Danny A. Zwijnenburg, Peter van Sluis, Linda J. Valentijn, Ida van der Ploeg, Mohamed Hamdi, Johan van Nes, Bart A. Westerman, Jennemiek van Arkel, Marli E. Ebus, Franciska Haneveld, Arjan Lakeman, Linda Schild, Piet Molenaar, Peter Stroeken, Max M. van Noesel, Ingrid Øra,, Evan E. Santo, Huib N. Caron, Ellen M. Westerhout, Rogier Versteeg Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes Nature 2012 Mar 8 Neuroblastoma Next Generation Sequencing Homo sapiens N481TL Complete Genomics hs8:19394927-19394927,hs8:128581556-128581556;hs8:128673342-128673342,hs8:128828072-128828072;hs6:31705218-31705218,hs6:169722886-169722886;hs11:77714161-77714161,hs17:25450547-25450547;hs11:77731716-77731716,hs17:25420373-25420373 ANO8;CWC22;FSIP2;GCDH;OIT3;SPTBN2;SVEP1;ZNF717 Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours. NCBI 36/hg18 EGAS00001000222 Yes NA CTDB0248 Research 22367537 Jan J. Molenaar, JanKoster, Danny A. Zwijnenburg, Peter van Sluis, Linda J. Valentijn, Ida van der Ploeg, Mohamed Hamdi, Johan van Nes, Bart A. Westerman, Jennemiek van Arkel, Marli E. Ebus, Franciska Haneveld, Arjan Lakeman, Linda Schild, Piet Molenaar, Peter Stroeken, Max M. van Noesel, Ingrid Øra,, Evan E. Santo, Huib N. Caron, Ellen M. Westerhout, Rogier Versteeg Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes Nature 2012 Mar 2 Neuroblastoma Next Generation Sequencing Homo sapiens N089TL Complete Genomics hs2:15259690-15259690,hs2:17211150-17211150;hs2:15437344-15437344,hs2:18841374-18841374;hs2:16002229-16002229,hs2:17494713-17494713;hs2:15276162-15276162,hs2:15594793-15594793;hs2:15284228-15284228,hs2:15435375-15435375;hsX:31276736-31276736,hsX:31626677-31626677;hs2:15143406-15143406,hs2:15564750-15564750;hs2:15217378-15217378,hs2:15597428-15597428;hs2:15488389-15488389,hs2:15648338-15648338;hs2:15614719-15614719,hs2:15634535-15634535;hs2:15648481-15648481,hs2:15950632-15950632;hs2:16079331-16079331,hs2:16932295-16932295;hs2:16221504-16221504,hs2:17046405-17046405;hs2:17894520-17894520,hs2:18522189-18522189;hs2:17926477-17926477,hs2:18518516-18518516;hs2:17931561-17931561,hs2:18241363-18241363;hs2:15140067-15140067,hs2:15743648-15743648;hs2:15219810-15219810,hs2:15723914-15723914;hs2:15232487-15232487,hs2:15904695-15904695;hs2:15380005-15380005,hs2:15836765-15836765;hs2:15482088-15482088,hs2:15708736-15708736;hs2:15482253-15482253,hs2:15938098-15938098;hs2:15896932-15896932,hs2:16149877-16149877;hs2:15955364-15955364,hs2:16004421-16004421;hs2:18040639-18040639,hs2:18789042-18789042;hs2:18084508-18084508,hs2:18842282-18842282;hs2:18238406-18238406,hs2:19028097-19028097;hs2:15651391-15651391,hs2:16045907-16045907;hs2:15035945-15035945,hs2:16009656-16009656;hs2:15614877-15614877,hs2:16057654-16057654;hs2:15616160-15616160,hs2:15650353-15650353 C7ORF31;PPFIA4;PROKR2;SCRIB;USP7 Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours. NCBI 36/hg18 EGAS00001000222 Yes NBAS,DDX1 CTDB0249 Research 22367537 Jan J. Molenaar, JanKoster, Danny A. Zwijnenburg, Peter van Sluis, Linda J. Valentijn, Ida van der Ploeg, Mohamed Hamdi, Johan van Nes, Bart A. Westerman, Jennemiek van Arkel, Marli E. Ebus, Franciska Haneveld, Arjan Lakeman, Linda Schild, Piet Molenaar, Peter Stroeken, Max M. van Noesel, Ingrid Øra,, Evan E. Santo, Huib N. Caron, Ellen M. Westerhout, Rogier Versteeg Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes Nature 2012 Mar 2 Neuroblastoma Next Generation Sequencing Homo sapiens N637TL Complete Genomics hs2:10458133-10458133,hs2:17135483-17135483;hs2:11805167-11805167,hs2:16140340-16140340;hs2:16025716-16025716,hs2:17563029-17563029;hs19:1215676-1215676,hs19:7820235-7820235;hs11:95222567-95222567,hs11:95223463-95223463;hs2:10321927-10321927,hs2:10362208-10362208;hs2:10321996-10321996,hs2:10367260-10367260;hs2:10348048-10348048,hs2:10367736-10367736;hs2:11658726-11658726,hs2:11867762-11867762;hs2:11658726-11658726,hs2:11867762-11867762;hs2:10359771-10359771,hs2:10545424-10545424;hs2:10426590-10426590,hs2:10524071-10524071;hs2:10265983-10265983,hs2:10530762-10530762;hs2:10266189-10266189,hs2:11720410-11720410;hs2:10367713-10367713,hs2:11216962-11216962;hs2:11821650-11821650,hs2:17823178-17823178;hs19:19496274-19496274,hs19:56017091-56017091 BNIPL;CIC;KRIT1;NPHP1;SLC17A7;ST6GAL2;TAS2R30 Department of Oncogenomics, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours. NCBI 36/hg18 EGAS00001000222 Yes C2orf48,NTSR2;GREB1,LPIN1;HPCAL1,PQLC3;LPIN1,GEN1 CTDB0250 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens MB-182 Illumina HiSeq 2000 PVT1;MYC Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,MYC CTDB0251 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens MB-506 Illumina HiSeq 2000 PVT1;MYC Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,MYC CTDB0252 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens MB-591 Illumina HiSeq 2000 PVT1;MYC Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,MYC CTDB0253 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens MB-586 Illumina HiSeq 2000 PVT1;NDRG1 Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,NDRG1 CTDB0254 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens MB-524 Illumina HiSeq 2000 PVT1;MYC Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,MYC CTDB0255 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens MB-1003 Illumina HiSeq 2000 PVT1;MYC Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,MYC CTDB0256 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens MB-1377 Illumina HiSeq 2000 PVT1;MYC Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,MYC CTDB0257 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens MB-1240 Illumina HiSeq 2000 PVT1;MYC Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,MYC CTDB0258 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens MB-1338 Illumina HiSeq 2000 PVT1;MYC Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,MYC CTDB0259 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens MB-548 Illumina HiSeq 2000 PVT1;MYC Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,MYC CTDB0260 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens D458 Illumina HiSeq 2000 PVT1;MYC Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,MYC CTDB0261 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens D425 Illumina HiSeq 2000 PVT1;MYC Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,MYC CTDB0262 Research 22832581 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD Subgroup-specific structural variation across 1,000 medulloblastoma genomes Nature 2012 Aug 8 Medulloblastoma Next Generation Sequencing Homo sapiens MED8A Illumina HiSeq 2000 PVT1;MYC Developmental & Stem Cell Biology Program, The Hospital for Sick Children,101 College Street, TMDT-11-401M, Toronto, Ontario M5G 1L7, Canada. Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4a. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kB signalling in Group 4, suggest future avenues for rational, targeted therapy. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. NCBI 36/hg18 GSE37385 EGAD00001000158 Yes PVT1,MYC CTDB0263 Research 22927308 Wu C, Wyatt AW, McPherson A, Lin D, McConeghy BJ, Mo F, Shukin R, Lapuk AV, Jones SJ, Zhao Y, Marra MA, Gleave ME, Volik SV, Wang Y, Sahinalp SC, Collins CC Poly-gene fusion transcripts and chromothripsis in prostate cancer. Genes Chromosomes Cancer 2012 Dec 1,8,12 Prostate cancer Next Generation Sequencing Homo sapiens LTL-313H Illumina Genome Analyzer II GRIN3B;MARCH10;ITGAE;CMYA5;SULT1C3;VN1R2;SLC2A9;AL160314.1;STARD8;SMC1B;DNAH6;KIF1A;KLHDC7A;SLC18A1;NOD2;TMX4;SPAG17;F13A1;STK31;RTTN;CXorf22;SYT6;FRAS1;CYB561;DNAH9;ATAD1;NR5A2;DACT1;STRA6;ZNF804B;NOTCH4;ACCN2;RAG1;PPPDE1;GPR98;CAPN14;FERMT1;TTN;DUOX1;KRT75;LRP4;FAT1;C12orf63;STARD13;ZNF192;DLGAP5;TRPV4;OAS1;SLC27A6;FAM55B;C14orf39;ERCC6;FRK;DMXL2;SYNPO2;ZMIZ1;TECTA;NAT8;TGFBR3;BTNL2;SCNN1B;UGT2B15;KIAA1109;ZBBX;NPBWR1;ODF3;AKR7L;RNF212;PDILT;C6orf170;EFHB;PAPLN;AC145676.2;SLC9A10;ARHGAP42;GNRHR2;YSK4;MMP26;FAM179A;SYDE2;OR5H2;SLC6A17;DNAH17;LCN8;C10orf131;SLC14A2;PTX4;C20orf201;SCD5;GSDMC;CRNKL1;CD6;VWDE;MYO7A;INPP5B;GSG2;IYD;OR2C1;PCDHA4;OR2W3;LMLN;DISC1;ZNF407;BCMO1;ADAMTSL1;SLCO1B3;HGF;FBXW12;C6orf97;CRYGB;AL353597.1;ALG8;TBC1D22A;SLC28A1;CX3CR1;ENG;AK7;ZFAT;GLI3;ZNF474;UNC13D;CELA2B;SUSD3;MUC5AC;ADNP2;GPR19;C7orf57;C11orf72;AMPH;BTN3A2;SPATA7;DNAH3;FAM57A;ANKS1B;TEP1;SCAND3;FAM196A;MBD5;HRNR;MARCH8;ZRANB3;SIVA1;FRMPD2;C9orf96;ATR;WDR27;DNAH14;THBS1;E2F7;ZNF681;KIAA1009;KALRN;PCLO;A2ML1;MATN2;GABRR2;FLG;ANKRD18B;SLC12A7;MSX1;GAB1;CIT;ATAD5;PDE4DIP;AC007601.1;DNAH7;MBOAT2;C19orf45;FNIP2;RPS27;CCDC141;KDM4D;SCFD2;ALPK1;MED12L;TRANK1;ALS2CR8;WDR78;C9orf171;FLG2;NLRP8;ARMC2;IFIH1;KIF21B;SLC7A8;NEU3;ZNF772;FAM161A;DNAH11;TCHH;NAV2;OTUD4;SCIN;PAQR5;MBLAC2;KIAA1211;SLC26A8;FTCD;SLC4A7;ANKRD44;LTN1;UTP20;ZNF519;KIAA0319;SV2C;PSMB8;DSC3;PTCH1;SEMG2;MLXIPL;SPZ1;ACAA2;LTK;DFFB;FAM186B;SETBP1;CLOCK;GLYATL3;BCAS1;LARP1;TOPBP1;TMPRSS3;EDAR;DNAH1;SLC5A4;TLN2;CECR2;EXPH5;URB2;C5orf42;MATN3;CAST;SPRY1;SRD5A1;ZNF184;TPO;THAP6;KDM1B;DECR2;CCDC48;AC083883.1;BIRC6;LRTOMT;IL28RA;OMA1;BRCA1;PDIA3;ZNF671;PLAC8L1;MYOF;CELSR2;PPARGC1B;TES;C9orf68;MFSD6;MRAP;ZNF484;GRIN3A;TARBP1;SPRED2;GLB1;MAN2B2;UBA6;SCAMP3;ZNF382;KIAA0556;VEZT;MLF1IP;TNKS1BP1;SP2;PARD3B;MAGI1;SON;EFHC1;TAF1D;WDR60;ZNF226;CLCN2;KIAA1324;MCM3AP;DNAJC2;SH3BP1;TSEN2;CHTF18;ST3GAL6;RASA1;COBLL1;DAGLB;NSD1;DOT1L;PPOX;SLC4A3;USPL1;SLC5A6;SCNN1D;UBN1;ODF3B;TOP3B;NMRAL1;DCP1B;EIF2AK1;CHID1;NAT10;SEC14L2;NUMB;ALDH3B2;RET;KIAA1543;SMARCA2;ZNF662;XXbac-B461K10.4;ZNF737;TRDMT1;POLN;ZNF584;MAPT;SMPDL3B;SCYL3;CAPN13;THADA;ACOT6;PKP2;C21orf59;DHX58;CCDC36;DNAJB7;ATM;C14orf145;CEP55;SLC38A9;CASP2;TOR1AIP1;RIN2;ZSWIM6;ZNF202;SGSM3;ERV3;TUBGCP5;NEIL3;ETAA1;MARCH3;ALG14;SEC16A;ESF1;C7orf63;CALML4;PPIF;CCDC66;CLCC1;DDX51;ANKRD12;ZDHHC6;MYNN;STAT2;NRSN2;SUPT16H;FAM184B;WNK2;CCDC85C;DMAP1;COMMD5;GALNT11;C14orf79;DERL3;WDR41;NCAPH2;PAAF1;ANKRD16;ITIH4;ZNF773;ACTR8;C1orf112;CHD7;SLC25A45;ANKK1;THEG;PLCH2;CTDSPL;PRDM15;CPT1A;STH;SLC23A1;ANKRD5;BLM;ADI1;SYNRG;AGMAT;MKI67;POP1;R3HDM1;RAD17;CWC22;PUS1;KRI1;DOM3Z;ZDHHC5;ZRANB2;CCT7;KIF15;TACC2;KIF13A;AC006547.14;LRRC63;CAPN12;CLMN;ARHGAP11A;OBSCN;MCF2L;NUPL2;CYP1A1;ARHGEF12;PREPL;SGOL2;HMMR;GTF3C3;GCC2;CCDC14;UIMC1;RSPH3;ZNF808;LIFR;CBS;LIMCH1;VSIG2;ARID5B;LTBP4;CCDC116;ZNF530;ZNF93;FEZ2;C10orf18;C9orf102;NOC3L;KIAA0802;RAB3GAP1;SYNE1;ZXDC;SMARCAL1;COX17;TCF20;ZNF830;ZNF708;USP8;LAMP1;PITRM1;ALG3;NKTR;MRPS15;DNAJC28;SDCCAG8;STON2;RPAP1;TRIOBP;CSMD3;CCDC138;PISD;ZNF440;GTPBP5;IQSEC1;SFI1;GEMIN5;PIK3R3;HYAL2;VKORC1L1;GTPBP10;PCDHB8;WDR76;NIT1;MOV10L1;TRAK2;DICER1;ABCC4;EMID2;SMC2;CASP9;GEN1;USP19;ZNF571;ABHD14B;IL4R;SLC22A18;NCDN;MUC20;OSCP1;NEK11;HES2;FBXO17;AC008074.1;ACTR1B;GFER;MYO6;DGKQ;HLA-DMA;SLC35C1;MARCH7;EFCAB10;TTC21B;PDZD2;PACRGL;C1orf50;CLK1;RP11-382J12.1;TCIRG1;PLEKHG2;GPATCH8;HNRNPF;IDUA;KTN1;ANKRD31;FBP2;C12orf43;ALMS1;F12;DOK7;IDO2;RHBDF2;FAM178B;C10orf62;FBF1;POFUT1;AKAP1;RGAG4;NUP210;PRKDC;YLPM1;AC127496.3;FAM186A;CYP2A7;SCN1B;TG;PI3;EXOC3;PM20D1;RP11-50B3.2;ZMAT4;SLC7A9;CXorf30;C2orf73;C10orf68;BSN;AC022415.1;SYNGR1;BCR;VTN;EPHA8;TP53;PCDHA1;C16orf46;RIBC2;CDKL5;UGGT2;CYP2D7P1;OCRL;RP4-695O20;SAC3D1 Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada Complex genome rearrangements are frequently observed in cancer but their impact on tumor molecular biology is largely unknown. Recent studies have identified a new phenomenon involving the simultaneous generation of tens to hundreds of genomic rearrangements, called chromothripsis. To understand the molecular consequences of these events, we sequenced the genomes and transcriptomes of two prostate tumors exhibiting evidence of chromothripsis. We identified several complex fusion transcripts, each containing sequence from three different genes, originating from different parts of the genome. One such poly-gene fusion transcript appeared to be expressed from a chain of small genomic fragments. Furthermore, we detected poly-gene fusion transcripts in the prostate cancer cell line LNCaP, suggesting they may represent a common phenomenon. Finally in one tumor with chromothripsis, we identified multiple mutations in the p53 signaling pathway, expanding on recent work associating aberrant DNA damage response mechanisms with chromothripsis. Overall, our data show that chromothripsis can manifest as massively rearranged transcriptomes. The implication that multigenic changes can give rise to poly-gene fusion transcripts is potentially of great significance to cancer genetics. NCBI 36/hg18 Yes ARF3,RUNX1T1;ATP6V1C1,TSTA3;BAALC,TRAPPC9;BCAT1,ATF7IP;BCAT1,LOH12CR1;BCAT1,TMTC2;C12orf59,TTLL9;C12orf59,UBE2V2;C6orf145,FARS2;C6orf145,PRPF4B;C6orf145,RNF165;CA2,C4BPA;CA2,RUNX1T1;CELSR1,PTDSS1;EEF1D,SDC4;KIAA1467,C12orf59;PACS1,PTEN;PDRG1,ARF3;PDRG1,RUNX1T1;PDRG1,ZNF623;PTDSS1,LOH12CR1;PTDSS1,SOX5;PTDSS1,SPRYD3;PTDSS1,UBE2V2;RNF165,SSR1;RUNX1T1,ARF3;RUNX1T1,C12orf35;RUNX1T1,HHAT;RUNX1T1,SDC4;RUNX1T1,SOX5;SDC4,PTDSS1;SLC25A21,C14ORF25;SLC35B1,PEMT;SLC35B11,PEMT;SLC6A17,CA2;SNX16,CA2;SPRYD3,PTDSS1;SSR1,RNF165;ST8SIA1,PDRG1;TENC1,TTLL9;TMPRSS2,ERG;TRAPPC9,SPRYD3;TRAPPC9,ZNF623;TTLL9,C12ORF57;TTLL9,C21orf59;TTLL9,KIAA1467;UCRC,C1orf194;USP34,AHSA2;USP34,C2orf74;ZNF623,TRAPPC9 CTDB0264 Research 22927308 Wu C, Wyatt AW, McPherson A, Lin D, McConeghy BJ, Mo F, Shukin R, Lapuk AV, Jones SJ, Zhao Y, Marra MA, Gleave ME, Volik SV, Wang Y, Sahinalp SC, Collins CC Poly-gene fusion transcripts and chromothripsis in prostate cancer. Genes Chromosomes Cancer 2012 Dec 6,10 Prostate cancer Next Generation Sequencing Homo sapiens LNCaP Illumina Genome Analyzer II Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada Complex genome rearrangements are frequently observed in cancer but their impact on tumor molecular biology is largely unknown. Recent studies have identified a new phenomenon involving the simultaneous generation of tens to hundreds of genomic rearrangements, called chromothripsis. To understand the molecular consequences of these events, we sequenced the genomes and transcriptomes of two prostate tumors exhibiting evidence of chromothripsis. We identified several complex fusion transcripts, each containing sequence from three different genes, originating from different parts of the genome. One such poly-gene fusion transcript appeared to be expressed from a chain of small genomic fragments. Furthermore, we detected poly-gene fusion transcripts in the prostate cancer cell line LNCaP, suggesting they may represent a common phenomenon. Finally in one tumor with chromothripsis, we identified multiple mutations in the p53 signaling pathway, expanding on recent work associating aberrant DNA damage response mechanisms with chromothripsis. Overall, our data show that chromothripsis can manifest as massively rearranged transcriptomes. The implication that multigenic changes can give rise to poly-gene fusion transcripts is potentially of great significance to cancer genetics. NCBI 36/hg18 Yes CYP2C19,PDE6C;CYP2C19,FAM190B;CYP2C18,SOD2;SNX9,CYP2C19 CTDB0265 Research 22927308 Wu C, Wyatt AW, McPherson A, Lin D, McConeghy BJ, Mo F, Shukin R, Lapuk AV, Jones SJ, Zhao Y, Marra MA, Gleave ME, Volik SV, Wang Y, Sahinalp SC, Collins CC Poly-gene fusion transcripts and chromothripsis in prostate cancer. Genes Chromosomes Cancer 2012 Dec 2,9 Prostate cancer Next Generation Sequencing Homo sapiens 890 Illumina Genome Analyzer II Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada Complex genome rearrangements are frequently observed in cancer but their impact on tumor molecular biology is largely unknown. Recent studies have identified a new phenomenon involving the simultaneous generation of tens to hundreds of genomic rearrangements, called chromothripsis. To understand the molecular consequences of these events, we sequenced the genomes and transcriptomes of two prostate tumors exhibiting evidence of chromothripsis. We identified several complex fusion transcripts, each containing sequence from three different genes, originating from different parts of the genome. One such poly-gene fusion transcript appeared to be expressed from a chain of small genomic fragments. Furthermore, we detected poly-gene fusion transcripts in the prostate cancer cell line LNCaP, suggesting they may represent a common phenomenon. Finally in one tumor with chromothripsis, we identified multiple mutations in the p53 signaling pathway, expanding on recent work associating aberrant DNA damage response mechanisms with chromothripsis. Overall, our data show that chromothripsis can manifest as massively rearranged transcriptomes. The implication that multigenic changes can give rise to poly-gene fusion transcripts is potentially of great significance to cancer genetics. NCBI 36/hg18 Yes FUBP1,ETV1;KCNS3,PPM1G;SLC35D2,LPPR1;SLC35D2,MRPL50;ZNF638,KCNS3 CTDB0266 Research 23334667 Brastianos PK, Horowitz PM, Santagata S, Jones RT, McKenna A, Getz G, Ligon KL, Palescandolo E, Van Hummelen P, Ducar MD, Raza A, Sunkavalli A, Macconaill LE, Stemmer-Rachamimov AO, Louis DN, Hahn WC, Dunn IF, Beroukhim R Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet 2013 Mar 1 Meningioma Next Generation Sequencing Homo sapiens MEN0017 Illumina HiSeq 2000 hs1:80589104-80589104,hs1:90870420-90870420;hs1:68000835-68000835,hs1:95538220-95538220;hs1:48880153-48880153,hs1:171741093-171741093;hs1:48881168-48881168,hs1:77612749-77612749;hs1:158828097-158828097,hs1:187549966-187549966;hs1:109163626-109163626,hs1:187277742-187277742;hs1:58421895-58421895,hs1:118155121-118155121;hs1:80323486-80323486,hs1:100225718-100225718;hs1:95875799-95875799,hs1:171930057-171930057;hs1:77604362-77604362,hs1:171918762-171918762;hs1:100228338-100228338,hs1:179526744-179526744;hs1:80320704-80320704,hs1:171918676-171918676;hs1:171933392-171933392,hs1:179641879-179641879;hs1:80320463-80320463,hs1:158825374-158825374;hs1:80319755-80319755,hs1:179527604-179527604;hs1:80323468-80323468,hs1:158825237-158825237;hs1:68000518-68000518,hs1:171929471-171929471;hs1:100228246-100228246,hs1:171917627-171917627;hs1:80325391-80325391,hs1:171922625-171922625;hs1:158828219-158828219,hs1:159614118-159614118;hs1:171749005-171749005,hs1:171938423-171938423;hs1:68020725-68020725,hs1:179524736-179524736;hs1:101963877-101963877,hs1:189981533-189981533;hs1:32007608-32007608,hs1:51630376-51630376;hs1:105077445-105077445,hs1:105098493-105098493;hs1:50367901-50367901,hs1:62435264-62435264;hs1:51793777-51793777,hs1:77595973-77595973;hs1:88831228-88831228,hs1:95948591-95948591;hs1:171921987-171921987,hs1:171951323-171951323;hs1:4200762-4200762,hs1:101186002-101186002;hs1:39578703-39578703,hs1:101398110-101398110;hs1:63343134-63343134,hs1:82455808-82455808;hs1:100224749-100224749,hs1:171930170-171930170;hs1:58439620-58439620,hs1:108360324-108360324;hs1:72006848-72006848,hs1:105092212-105092212;hs1:100224110-100224110,hs1:171938268-171938268;hs1:48879478-48879478,hs1:80328473-80328473;hs1:38050332-38050332,hs1:39576150-39576150;hs1:179524915-179524915,hs1:189943790-189943790;hs1:68005693-68005693,hs1:100225462-100225462;hs1:102483233-102483233,hs1:105090171-105090171;hs1:68030155-68030155,hs1:149394091-149394091;hs12:113888190-113888190,hs12:113889327-113889327;hs6:125047720-125047720,hsX:140770594-140770594 NEGR1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA Meningiomas are the most common primary nervous system tumor. The tumor suppressor NF2 is disrupted in approximately half of all meningiomas, but the complete spectrum of genetic changes remains undefined. We performed whole-genome or whole-exome sequencing on 17 meningiomas and focused sequencing on an additional 48 tumors to identify and validate somatic genetic alterations. Most meningiomas had simple genomes, with fewer mutations, rearrangements and copy-number alterations than reported in other tumors in adults. However, several meningiomas harbored more complex patterns of copy-number changes and rearrangements, including one tumor with chromothripsis. We confirmed focal NF2 inactivation in 43% of tumors and found alterations in epigenetic modifiers in an additional 8% of tumors. A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. These results begin to define the spectrum of genetic alterations in meningiomas and identify potential therapeutic targets. GRCh37/hg19 phs000552 Yes AGBL4,INADL;DAB1,FAM46C;DAB1,VAV3;DNM3,TDRD5;FRRS1,DNM3;FRRS1,NPHS2;GNL2,MACF1;MACF1,SLC30A7;METTL13,DNM3;PIGK,DNM3;SPATA6,PIGK;TTC39A,PIGK CTDB0267 Research 22388000 Chiang C, Jacobsen JC, Ernst C, Hanscom C, Heilbut A, Blumenthal I, Mills RE, Kirby A, Lindgren AM, Rudiger SR, McLaughlan CJ, Bawden CS, Reid SJ, Faull RL, Snell RG, Hall IM, Shen Y, Ohsumi TK, Borowsky ML, Daly MJ, Lee C, Morton CC, MacDonald ME, Gusella JF, Talkowski ME Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Nat Genet 2012 Mar 5,X Germline Next Generation Sequencing Homo sapiens BSID42 Illumina HiSeq 2000 hsX:110368673-110368673,hs5:90466028-90466028;hs5:90502468-90502468,hsX:130567294-130567294;hs5:90711091-90711091,hs5:90892029-90892029;hs5:90892144-90892144,hsX:131442883-131442883;hsX:110368663-110368663,hs5:90719199-90719199;hsX:131438029-131438029,hs5:92483810-92483810;hs5:90494025-90494025,hs5:90892027-90892027;hs5:90494024-90494024,hs5:90502468-90502468;hs5:90691787-90691787,hs5:90886192-90886192;hs5:92932823-92932823,hs5:90693163-90693163;hs5:92483805-92483805,hs5:90719148-90719148;hs5:90892142-90892142,hs5:90466010-90466010;hs5:90886193-90886193,hs5:92932823-92932823;hsX:130567294-130567294,hs5:90711016-90711016 Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations. GRCh37/hg19 No NA CTDB0268 Research 22388000 Chiang C, Jacobsen JC, Ernst C, Hanscom C, Heilbut A, Blumenthal I, Mills RE, Kirby A, Lindgren AM, Rudiger SR, McLaughlan CJ, Bawden CS, Reid SJ, Faull RL, Snell RG, Hall IM, Shen Y, Ohsumi TK, Borowsky ML, Daly MJ, Lee C, Morton CC, MacDonald ME, Gusella JF, Talkowski ME Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Nat Genet 2012 Mar 3,5,7 Germline Next Generation Sequencing Homo sapiens BSID43 Illumina HiSeq 2000 hs3:155627600-155627600,hs7:120004011-120004011;hs7:119889673-119889673,hs3:155627601-155627601;hs3:152159406-152159406,hs7:119999922-119999922;hs7:120765008-120765008,hs3:152159406-152159406;hs7:119646830-119646830,hs7:120254239-120254239;hs7:119889690-119889690,hs7:119646829-119646829;hs7:119995774-119995774,hs7:119999919-119999919;hs7:122606556-122606556,hs7:120254240-120254240;hs5:87073891-87073891,hs7:119995778-119995778;hs7:122606486-122606486,hs5:87073908-87073908;hs7:120004010-120004010,hs7:120766450-120766450 Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations. GRCh37/hg19 No NA CTDB0269 Research 22608083 Nik-Zainal S, Van Loo P, Wedge DC, Alexandrov LB, Greenman CD, Lau KW, Raine K, Jones D, Marshall J, Ramakrishna M, Shlien A, Cooke SL, Hinton J, Menzies A, Stebbings LA, Leroy C, Jia M, Rance R, Mudie LJ, Gamble SJ, Stephens PJ, McLaren S, Tarpey PS, Papaemmanuil E, Davies HR, Varela I, McBride DJ, Bignell GR, Leung K, Butler AP, Teague JW, Martin S, Jonsson G, Mariani O, Boyault S, Miron P, Fatima A, Langerod A, Aparicio SA, Tutt A, Sieuwerts AM, Borg A, Thomas G, Salomon AV, Richardson AL, Borresen-Dale AL, Futreal PA, Stratton MR, Campbell PJ; Breast Cancer Working Group of the International Cancer Genome Consortium The life history of 21 breast cancers Cell 2012 May 2,4,18,21 Breast cancer Next Generation Sequencing Homo sapiens PD4120a Illumina GAIIx or Hiseq 2000 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis. GRCh37/hg19 Yes NA CTDB0270 Research 22608084 Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P, Greenman CD, Raine K, Jones D, Hinton J, Marshall J, Stebbings LA, Menzies A, Martin S, Leung K, Chen L, Leroy C, Ramakrishna M, Rance R, Lau KW, Mudie LJ, Varela I, McBride DJ, Bignell GR, Cooke SL, Shlien A, Gamble J, Whitmore I, Maddison M, Tarpey PS, Davies HR, Papaemmanuil E, Stephens PJ, McLaren S, Butler AP, Teague JW, Jonsson G, Garber JE, Silver D, Miron P, Fatima A, Boyault S, Langerod A, Tutt A, Martens JW, Aparicio SA, Borg A, Salomon AV, Thomas G, Borresen-Dale AL, Richardson AL, Neuberger MS, Futreal PA, Campbell PJ, Stratton MR; Breast Cancer Working Group of the International Cancer Genome Consortium Mutational processes molding the genomes of 21 breast cancers Cell 2012 May 6 Breast cancer Next Generation Sequencing Homo sapiens PD4107a Illumina GAIIx or Hiseq 2000 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed kataegis, was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed. GRCh37/hg19 Yes NA CTDB0271 Research 22980976 Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, Maher CA, Fulton R, Fulton L, Wallis J, Chen K, Walker J, McDonald S, Bose R, Ornitz D, Xiong D, You M, Dooling DJ, Watson M, Mardis ER, Wilson RK Genomic landscape of non-small cell lung cancer in smokers and never-smokers Cell 2012 Sep 5,10,12,17,20 Non Small-cell lung cancer Next Generation Sequencing Homo sapiens LUC7 Illumina chr10:0-42644756:0;chr10:42644757-42644997:1;chr10:42644998-42680939:0;chr10:42680940-42681264:1;chr10:42681265-42832236:0;chr10:42832237-42833689:1;chr10:42833690-42903614:0;chr10:42903615-42970797:1;chr10:42970798-42970989:0;chr10:42970990-42990784:1;chr10:42990785-43008961:0;chr10:43008962-43048280:1;chr10:43048281-43062123:0;chr10:43062124-43062931:1;chr10:43062932-43156174:0;chr10:43156175-43157224:1;chr10:43157225-43169643:0;chr10:43169644-43187171:1;chr10:43187172-43189817:0;chr10:43189818-43210023:1;chr10:43191482-43201901:1;chr10:43210024-43221303:0;chr10:43221304-43232607:1;chr10:43232608-43277952:0;chr10:43277953-43330385:1;chr10:43330386-43366967:0;chr10:43366968-43369508:1;chr10:43369509-43474463:0;chr10:43474464-43476955:1;chr10:43476956-43572473:0;chr10:43572474-43625799:1;chr10:43625800-43633932:0;chr10:43633933-43680756:1;chr10:43680757-43689981:0;chr10:43689982-43762367:1;chr10:43762368-44124263:0;chr10:44124264-44170151:1;chr10:44126329-44127012:1;chr10:44126394-44126830:1;chr10:44170152-44236883:0;chr10:44236884-44237798:1;chr10:44237799-44273008:0;chr10:44273009-44274273:1;chr10:44274274-44340752:0;chr10:44340753-44346070:1;chr10:44346071-44407890:0;chr10:44407891-44409684:1;chr10:44409346-44409954:1;chr10:44409955-44434449:0;chr10:44434450-44439914:1;chr10:44439915-44755048:0;chr10:44755049-44757261:1;chr10:44757262-44787704:0;chr10:44787705-44789157:1;chr10:44789158-44793036:0;chr10:44793037-44881941:1;chr10:44881942-44910095:0;chr10:44910096-44910601:1;chr10:44910602-45086654:0;chr10:45086655-45097552:1;chr10:45097553-46111037:0;chr10:46111038-46168261:1;chr10:46168262-46951470:0;chr10:46951471-46966835:1;chr10:46952761-46971400:1;chr10:46971401-46993544:0;chr10:46993545-47005643:1;chr10:47005644-47011751:0;chr10:47011752-47174018:1;chr10:47083533-47088320:1;chr10:47096453-47099716:1;chr10:47133337-47133898:1;chr10:47174019-47556163:0;chr10:47556164-47566804:1;chr10:47566805-47594377:0;chr10:47594378-47595651:1;chr10:47595652-47620143:0;chr10:47620144-47644793:1;chr10:47644794-47658232:0;chr10:47658233-47701446:1;chr10:47701447-48324786:0;chr10:48324787-48332197:1;chr10:48332198-48355022:0;chr10:48355023-48373866:1;chr10:48357925-48358600:1;chr10:48373867-48381485:0;chr10:48381486-48390991:1;chr10:48390992-48413090:0;chr10:48413091-48416853:1;chr10:48416854-48425783:0;chr10:48425784-48439166:1;chr10:48439167-49360854:0;chr10:49360855-49482941:1;chr10:49407710-49409697:1;chr10:49482942-49500740:0;chr10:49500741-49501460:1;chr10:49501461-49514688:0;chr10:49514689-49647403:1;chr10:49647404-49654075:0;chr10:49654076-49864310:1;chr10:49718567-49719632:1;chr10:49754516-49754758:1;chr10:49832048-49833138:1;chr10:49864311-49872242:0;chr10:49872243-49880469:1;chr10:49880470-50184595:0;chr10:50184596-50186927:1;chr10:50186928-50192607:0;chr10:50192608-50226942:1;chr10:50222332-50323559:1;chr10:50323560-50329882:0;chr10:50329883-50359592:1;chr10:50339198-50342065:1;chr10:50359593-50362771:0;chr10:50362772-50396630:1;chr10:50396631-50504155:0;chr10:50504156-50507063:1;chr10:50507064-50507185:0;chr10:50507186-50535537:1;chr10:50535538-50572235:0;chr10:50572236-50603986:1;chr10:50603987-50627321:0;chr10:50627322-50680949:1;chr10:50663413-50747584:1;chr10:50723150-50747584:1;chr10:50747585-50817139:0;chr10:50817140-50901939:1;chr10:50818346-50820766:1;chr10:50887683-50918307:1;chr10:50911034-50911419:1;chr10:50918308-50942685:0;chr10:50942686-50970425:1;chr10:50970426-50979885:0;chr10:50979886-50981345:1;chr10:50981346-51023140:0;chr10:51023141-51023608:1;chr10:51023609-51532100:0;chr10:51532101-51532572:1;chr10:51532573-51535124:0;chr10:51535125-51535474:1;chr10:51535475-51549496:0;chr10:51549497-51562590:1;chr10:51562591-51565106:0;chr10:51565107-51590734:1;chr10:51590735-52024736:0;chr10:52024737-52026575:1;chr10:52026576-52065343:0;chr10:52065344-52384923:1;chr10:52232573-52234006:1;chr10:52384924-135374737:0;chr11:0-134452384:0;chr12:0-55224301:0;chr12:55224302-55252177:1;chr12:55252178-55341800:0;chr12:55341801-55378530:1;chr12:55378531-55413727:0;chr12:55413728-55423801:1;chr12:55423802-55587664:0;chr12:55587665-55588570:1;chr12:55588571-55640980:0;chr12:55640981-55642086:1;chr12:55642087-55656321:0;chr12:55656322-55657215:1;chr12:55657216-55705617:0;chr12:55705618-55706541:1;chr12:55706542-55714343:0;chr12:55714344-55715408:1;chr12:55715409-55770580:0;chr12:55770581-55771520:1;chr12:55771521-55782227:0;chr12:55782228-55783158:1;chr12:55783159-55794212:0;chr12:55794213-55795289:1;chr12:55795290-55845996:0;chr12:55845997-55846936:1;chr12:55846937-55862982:0;chr12:55862983-55863922:1;chr12:55863923-57316936:0;chr12:57316937-57328189:1;chr12:57328190-57345214:0;chr12:57345215-57353158:1;chr12:57348915-57400297:1;chr12:57388229-57390469:1;chr12:57400298-57403779:0;chr12:57403780-57422667:1;chr12:57422300-57444982:1;chr12:57444983-57449424:0;chr12:57449425-57481846:1;chr12:57481847-57489185:0;chr12:57489186-57525922:1;chr12:57522275-57607134:1;chr12:57588286-57588359:1;chr12:57607135-57610576:0;chr12:57610577-57620232:1;chr12:57620233-57623108:0;chr12:57623109-57628718:1;chr12:57628685-57634498:1;chr12:57634499-57637234:0;chr12:57637235-57644976:1;chr12:57643391-57824788:1;chr12:57824789-57828525:0;chr12:57828526-57845842:1;chr12:57845843-57846104:0;chr12:57846105-57853063:1;chr12:57853064-57853916:0;chr12:57853917-57866047:1;chr12:57866037-57882597:1;chr12:57869227-57911352:1;chr12:57910370-57914300:1;chr12:57912945-57913042:1;chr12:57914301-57914491:0;chr12:57914492-57923931:1;chr12:57923884-57941114:1;chr12:57941115-57943779:0;chr12:57943780-57980415:1;chr12:57980416-57984940:0;chr12:57984941-57997211:1;chr12:57997212-57998403:0;chr12:57998404-58003587:1;chr12:58003588-58003961:0;chr12:58003962-58013162:1;chr12:58005900-58011848:1;chr12:58013163-58013308:0;chr12:58013309-58019934:1;chr12:58017192-58027138:1;chr12:58027139-58068446:0;chr12:58068447-58069027:1;chr12:58069028-58087736:0;chr12:58087737-58115340:1;chr12:58115341-58118074:0;chr12:58118075-58135944:1;chr12:58131795-58143994:1;chr12:58141509-58149796:1;chr12:58148880-58154193:1;chr12:58154194-58156115:0;chr12:58156116-58161034:1;chr12:58161035-58162252:0;chr12:58162253-58166576:1;chr12:58166382-58176323:1;chr12:58166810-58201854:1;chr12:58191158-58212487:1;chr12:58212488-58213708:0;chr12:58213709-58240747:1;chr12:58218391-58218475:1;chr12:58240748-58251211:0;chr12:58251212-58251448:1;chr12:58251449-58335322:0;chr12:58335323-58351052:1;chr12:58351053-64238071:0;chr12:64238072-64541613:1;chr12:64495947-64496033:1;chr12:64541614-64580094:0;chr12:64580095-64616076:1;chr12:64616077-64660761:0;chr12:64660762-64784471:1;chr12:64784472-65107220:0;chr12:65107221-65153227:1;chr12:65153228-67663059:0;chr12:67663060-67713731:1;chr12:67713732-67766645:0;chr12:67766646-67766781:1;chr12:67766782-68042116:0;chr12:68042117-68059186:1;chr12:68059187-68395175:0;chr12:68395176-68395328:1;chr12:68395329-68548546:0;chr12:68548547-68553527:1;chr12:68553528-68595127:0;chr12:68595128-68619601:1;chr12:68619602-68642020:0;chr12:68642021-68647387:1;chr12:68647388-68666221:0;chr12:68666222-68726161:1;chr12:68726162-68946773:0;chr12:68946774-68947662:1;chr12:68947663-69004617:0;chr12:69004618-69054385:1;chr12:69021013-69021155:1;chr12:69054386-69078373:0;chr12:69078374-69080085:1;chr12:69080086-69080512:0;chr12:69080513-69136785:1;chr12:69099413-69100846:1;chr12:69136786-69139884:0;chr12:69139885-69187744:1;chr12:69186124-69187743:1;chr12:69187745-69201954:0;chr12:69201955-69239214:1;chr12:69235976-69365350:1;chr12:69365351-69511346:0;chr12:69511347-69511432:1;chr12:69511433-69593907:0;chr12:69593908-69593979:1;chr12:69593980-69633315:0;chr12:69633316-69668138:1;chr12:69668139-69742119:0;chr12:69742120-69748014:1;chr12:69748015-69753481:0;chr12:69753482-69784576:1;chr12:69784577-69816439:0;chr12:69816440-69816772:1;chr12:69816773-69979112:0;chr12:69979113-69995357:1;chr12:69995358-70002343:0;chr12:70002344-70004942:1;chr12:70004943-70037138:0;chr12:70037139-70093256:1;chr12:70093257-70132459:0;chr12:70132460-70216984:1;chr12:70216985-70219082:0;chr12:70219083-70352877:1;chr12:70352878-70636772:0;chr12:70636773-70748773:1;chr12:70748774-132349534:0;chr13:0-114142980:0;chr14:0-106368585:0;chr15:0-100338915:0;chr16:0-88827254:0;chr17:0-48016484:0;chr17:48016485-48017183:1;chr17:48017184-48046332:0;chr17:48046333-48052323:1;chr17:48052324-48067367:0;chr17:48067368-48072588:1;chr17:48072589-48074251:0;chr17:48074252-48094208:1;chr17:48094209-53469972:0;chr17:53469973-53499341:1;chr17:53499342-53604323:0;chr17:53604324-53638452:1;chr17:53638453-53796986:0;chr17:53796987-53809482:1;chr17:53809483-53828338:0;chr17:53828339-53854748:1;chr17:53854749-54230834:0;chr17:54230835-54560007:1;chr17:54560008-78774742:0;chr18:0-76117153:0;chr19:0-63811651:0;chr1:0-247249719:0;chr20:0-58090244:0;chr20:58090245-58091094:1;chr20:58091095-62435964:0;chr21:0-46944323:0;chr22:0-49691432:0;chr2:0-242951149:0;chr3:0-199501827:0;chr4:0-191273063:0;chr5:0-107929308:0;chr5:107929309-107929668:-1;chr5:107929669-108061404:0;chr5:108061405-108063994:-1;chr5:108063995-108083521:0;chr5:108083522-108532542:-1;chr5:108119798-108121240:-1;chr5:108153741-108166491:-1;chr5:108532543-108572819:0;chr5:108572820-108662070:-1;chr5:108662071-108803052:0;chr5:108803053-108803653:-1;chr5:108803654-108806542:0;chr5:108806543-108807287:-1;chr5:108807288-108833576:0;chr5:108833577-108834809:-1;chr5:108834810-108924037:0;chr5:108924038-108925293:-1;chr5:108925294-109025065:0;chr5:109025066-109205326:-1;chr5:109175828-109176393:-1;chr5:109205327-109624932:0;chr5:109624933-110074657:-1;chr5:110074658-110283726:0;chr5:110283727-110286479:-1;chr5:110286480-110306648:0;chr5:110306649-110344598:-1;chr5:110319261-110320165:-1;chr5:110344599-110405758:0;chr5:110405759-110413722:-1;chr5:110413723-110427412:0;chr5:110427413-110481518:-1;chr5:110481519-110490940:0;chr5:110490941-110491850:-1;chr5:110491851-110527922:0;chr5:110527923-110528740:-1;chr5:110528741-110559349:0;chr5:110559350-110830584:-1;chr5:110601506-110605787:-1;chr5:110613214-110638265:-1;chr5:110830585-110831729:0;chr5:110831730-110848288:-1;chr5:110847923-111075423:-1;chr5:110891592-110891678:-1;chr5:110998317-111333161:-1;chr5:111333162-111478136:0;chr5:111478137-111755013:-1;chr5:111496222-111499973:-1;chr5:111497181-111497314:-1;chr5:111509266-111511245:-1;chr5:111527716-111545836:-1;chr5:111755014-111964131:0;chr5:111964132-111967797:-1;chr5:111967798-112043193:0;chr5:112043194-112203279:-1;chr5:112196884-112228776:-1;chr5:112228777-112357794:0;chr5:112357795-112824527:-1;chr5:112658724-112772871:-1;chr5:112768250-112770728:-1;chr5:112824528-112849378:0;chr5:112849379-112930984:-1;chr5:112930985-113391701:0;chr5:113391702-113392871:-1;chr5:113392872-113696664:0;chr5:113696665-113832321:-1;chr5:113783114-114109110:-1;chr5:113911737-113915667:-1;chr5:114109111-114366968:0;chr5:114366969-114367591:-1;chr5:114367592-114423587:0;chr5:114423588-114424172:-1;chr5:114424173-114460457:0;chr5:114460458-114516243:-1;chr5:114484460-114485341:-1;chr5:114516244-114524258:0;chr5:114524259-114524629:-1;chr5:114524630-114546525:0;chr5:114546526-114598569:-1;chr5:114546530-114573818:-1;chr5:114598570-114600348:0;chr5:114600349-114601214:-1;chr5:114601215-114602883:0;chr5:114602884-114632528:-1;chr5:114632529-114847772:0;chr5:114847773-114849391:-1;chr5:114849392-114856606:0;chr5:114856607-114880591:-1;chr5:114880592-115298149:0;chr5:115298150-115363316:-1;chr5:115310261-115311972:-1;chr5:115363317-115365713:0;chr5:115365714-115365808:-1;chr5:115365809-115387605:0;chr5:115387606-115387986:-1;chr5:115387987-115389705:0;chr5:115389706-115394634:-1;chr5:115394635-115420686:0;chr5:115420687-115748459:-1;chr5:115638050-115639831:-1;chr5:115748460-115779249:0;chr5:115779250-115910630:-1;chr5:115780103-115780830:-1;chr5:115783242-115843972:-1;chr5:115910631-116051927:0;chr5:116051928-116052387:-1;chr5:116052388-116078685:0;chr5:116078686-116097905:-1;chr5:116097906-116366894:0;chr5:116366895-116374265:-1;chr5:116374266-116636798:0;chr5:116636799-116637138:-1;chr5:116637139-116751203:0;chr5:116751204-116881993:-1;chr5:116881994-117054933:0;chr5:117054934-117057792:-1;chr5:117057793-117260701:0;chr5:117260702-117601730:-1;chr5:117601731-117618268:0;chr5:117618269-117620477:-1;chr5:117620478-117803849:0;chr5:117803850-117897812:-1;chr5:117897813-117911268:0;chr5:117911269-117917019:-1;chr5:117917020-118093904:0;chr5:118093905-118093969:-1;chr5:118093970-118096167:0;chr5:118096168-118121154:-1;chr5:118121155-118345753:0;chr5:118345754-118346237:-1;chr5:118346238-118347164:0;chr5:118347165-118347751:-1;chr5:118347752-118604385:0;chr5:118604386-118730294:-1;chr5:118730295-118882824:0;chr5:118882825-118883301:-1;chr5:118883302-119015890:0;chr5:119015891-119016775:-1;chr5:119016776-119799971:0;chr5:119799972-120023027:-1;chr5:120023028-120116911:0;chr5:120116912-120126473:-1;chr5:120126474-120366879:0;chr5:120366880-120379700:-1;chr5:120379701-120394937:0;chr5:120394938-120396648:-1;chr5:120396649-120531673:0;chr5:120531674-120531905:-1;chr5:120531906-120658243:0;chr5:120658244-120661532:-1;chr5:120661533-121007066:0;chr5:121007067-121007567:-1;chr5:121007568-121297654:0;chr5:121297655-121411265:-1;chr5:121398889-121414206:-1;chr5:121414207-121464455:0;chr5:121464456-121490551:-1;chr5:121465207-121515312:-1;chr5:121490190-121491710:-1;chr5:121493062-121518353:-1;chr5:121518354-121647047:0;chr5:121647048-121799914:-1;chr5:121656985-121659053:-1;chr5:121772191-121814782:-1;chr5:121814783-122011852:0;chr5:122011853-122012450:-1;chr5:122012451-125515268:0;chr5:125515269-125529543:-1;chr5:125529544-125695786:0;chr5:125695787-125832186:-1;chr5:125769196-125826063:-1;chr5:125832187-126478772:0;chr5:126478773-126478939:-1;chr5:126478940-126506225:0;chr5:126506226-126507958:-1;chr5:126507959-126515446:0;chr5:126515447-126515592:-1;chr5:126515593-126626454:0;chr5:126626455-126801429:-1;chr5:126801430-126801512:0;chr5:126801513-126801810:-1;chr5:126801811-126853299:0;chr5:126853300-126890782:-1;chr5:126890783-128430384:0;chr5:128430385-128449721:-1;chr5:128449722-128795250:0;chr5:128795251-128796382:-1;chr5:128795957-129074376:-1;chr5:128836053-129241610:-1;chr5:129240164-129522327:-1;chr5:129475723-129477643:-1;chr5:129522328-130325588:0;chr5:130325589-130326121:-1;chr5:130326122-130329945:0;chr5:130329946-130331857:-1;chr5:130331858-130344274:0;chr5:130344275-130344435:-1;chr5:130344436-130494718:0;chr5:130494719-130507428:-1;chr5:130507429-130759612:0;chr5:130759613-131132756:-1;chr5:130761583-131132756:-1;chr5:131132757-131483182:0;chr5:131483183-131485252:-1;chr5:131485253-131520567:0;chr5:131520568-131528501:-1;chr5:131528502-131528677:0;chr5:131528678-131529261:-1;chr5:131529262-131535147:0;chr5:131535148-131539180:-1;chr5:131539181-131746326:0;chr5:131746327-131811736:-1;chr5:131811737-132083135:0;chr5:132083136-132089856:-1;chr5:132089857-132723463:0;chr5:132723464-132724241:-1;chr5:132724242-133603110:0;chr5:133603111-133603547:-1;chr5:133603548-134456214:0;chr5:134456215-134475371:-1;chr5:134475372-134669588:0;chr5:134669589-134735604:-1;chr5:134735605-134786301:0;chr5:134786302-134794387:-1;chr5:134794388-135148354:0;chr5:135148355-135162271:-1;chr5:135162272-135170336:0;chr5:135170337-135224326:-1;chr5:135224327-135227933:0;chr5:135227934-135231516:-1;chr5:135231517-135266004:0;chr5:135266005-135287280:-1;chr5:135287281-135364582:0;chr5:135364583-135399507:-1;chr5:135399508-135465194:0;chr5:135465195-135470579:-1;chr5:135470580-135712034:0;chr5:135712035-135732730:-1;chr5:135732731-135802364:0;chr5:135802365-135855987:-1;chr5:135855988-136193315:0;chr5:136193316-136194031:-1;chr5:136194032-137086114:0;chr5:137086115-137090065:-1;chr5:137088165-137090020:-1;chr5:137090066-138614467:0;chr5:138614468-138614668:-1;chr5:138614669-139579746:0;chr5:139579747-139582772:-1;chr5:139582773-139927249:0;chr5:139927250-139929163:-1;chr5:139929164-139944039:0;chr5:139944040-139948688:-1;chr5:139948689-140071009:0;chr5:140071010-140078890:-1;chr5:140078891-140090858:0;chr5:140090859-140090958:-1;chr5:140090959-140098508:0;chr5:140098509-140098598:-1;chr5:140098599-140111873:0;chr5:140111874-140112448:-1;chr5:140112449-140143693:0;chr5:140143694-140144406:-1;chr5:140144407-140240339:0;chr5:140240340-140243224:-1;chr5:140240859-140243104:-1;chr5:140243225-140514798:0;chr5:140514799-140517712:-1;chr5:140517713-140560978:0;chr5:140560979-140565974:-1;chr5:140565975-140613936:0;chr5:140613937-140617101:-1;chr5:140617102-140698055:0;chr5:140698056-140700351:-1;chr5:140699660-140700339:-1;chr5:140700352-140710202:0;chr5:140710203-140892546:-1;chr5:140805852-140808219:-1;chr5:140810157-140892546:-1;chr5:140855568-140892546:-1;chr5:140858882-140859192:-1;chr5:140892547-142125163:0;chr5:142125164-142140563:-1;chr5:142140564-142149947:0;chr5:142149948-142608576:-1;chr5:142608577-142755191:0;chr5:142755192-142755448:-1;chr5:142755449-143131661:0;chr5:143131662-143132269:-1;chr5:143132270-143191724:0;chr5:143191725-143200284:-1;chr5:143200285-143520442:0;chr5:143520443-143520681:-1;chr5:143520682-143537721:0;chr5:143537722-143550278:-1;chr5:143550279-143550394:0;chr5:143550395-143856944:-1;chr5:143856945-143901701:0;chr5:143901702-143902551:-1;chr5:143902552-144381464:0;chr5:144381465-144385352:-1;chr5:144385353-144717493:0;chr5:144717494-144761233:-1;chr5:144761234-144809429:0;chr5:144809430-144830662:-1;chr5:144830663-144851360:0;chr5:144851361-145214932:-1;chr5:145107922-145108912:-1;chr5:145214933-145239294:0;chr5:145239295-145252531:-1;chr5:145252532-145316124:0;chr5:145316125-145461354:-1;chr5:145376780-145377566:-1;chr5:145461355-145463874:0;chr5:145463875-145483946:-1;chr5:145478968-145499975:-1;chr5:145499976-145780542:0;chr5:145780543-145786922:-1;chr5:145786923-145892664:0;chr5:145892665-145895753:-1;chr5:145895754-146035962:0;chr5:146035963-146299069:-1;chr5:146085943-146087163:-1;chr5:146299070-148441874:0;chr5:148441875-148441972:1;chr5:148441973-149372679:0;chr5:149372680-149380730:1;chr5:149379883-149432706:1;chr5:149394347-149394717:1;chr5:149401129-149401484:1;chr5:149432707-149432852:0;chr5:149432853-149492935:1;chr5:149473859-149474619:1;chr5:149492936-150273952:0;chr5:150273953-150284545:1;chr5:150284546-150748003:0;chr5:150748004-150748076:1;chr5:150748077-156693087:0;chr5:156693088-156822606:-1;chr5:156768606-156772729:-1;chr5:156802748-156811947:-1;chr5:156822607-157170701:0;chr5:157170702-157187717:-1;chr5:157187718-158584415:0;chr5:158584416-158637061:-1;chr5:158637062-158741789:0;chr5:158741790-158757895:-1;chr5:158757896-167956508:0;chr5:167956509-167957639:1;chr5:167957640-167975498:0;chr5:167975499-168006614:1;chr5:168006615-168088743:0;chr5:168088744-168728133:1;chr5:168195150-168195260:1;chr5:168420004-168422682:1;chr5:168440231-168465003:1;chr5:168687048-168687139:1;chr5:168690604-168690698:1;chr5:168728134-169010636:0;chr5:169010637-169031782:1;chr5:169031783-169064249:0;chr5:169064250-169510386:1;chr5:169290718-169407744:1;chr5:169510387-169532899:0;chr5:169532900-169536729:1;chr5:169536730-169659449:0;chr5:169659450-169679579:1;chr5:169673240-169725231:1;chr5:169725232-169780489:0;chr5:169780490-170163636:1;chr5:169805166-169816681:1;chr5:170163637-170190352:0;chr5:170190353-170241051:1;chr5:170241052-170288872:0;chr5:170288873-170727019:1;chr5:170293838-170294148:1;chr5:170727020-170736286:0;chr5:170736287-170739528:1;chr5:170739529-170814118:0;chr5:170814119-170838141:1;chr5:170838142-170846658:0;chr5:170846659-170884630:1;chr5:170884631-171212874:0;chr5:171212875-171221602:1;chr5:171221603-171288551:0;chr5:171288552-171433877:1;chr5:171433878-171469072:0;chr5:171469073-171615390:1;chr5:171615391-171621174:0;chr5:171621175-171630458:1;chr5:171630459-171636642:0;chr5:171636643-171711075:1;chr5:171706205-171706319:1;chr5:171711076-171752183:0;chr5:171752184-171881527:1;chr5:171866666-171866758:1;chr5:171881528-172068267:0;chr5:172068268-172118543:1;chr5:172118544-172195091:0;chr5:172195092-172198203:1;chr5:172198204-172261221:0;chr5:172261222-172379688:1;chr5:172379689-172385730:0;chr5:172385731-172396774:1;chr5:172396775-172410758:0;chr5:172410759-172462448:1;chr5:172447728-172447932:1;chr5:172462449-172483353:0;chr5:172483354-172566291:1;chr5:172566292-172571443:0;chr5:172571444-172591390:1;chr5:172591391-172631030:0;chr5:172631031-172631095:1;chr5:172631096-172659105:0;chr5:172659106-172662360:1;chr5:172662361-172720130:0;chr5:172720131-172721732:1;chr5:172721733-172741714:0;chr5:172741715-172756506:1;chr5:172756507-180857866:0;chr6:0-170899992:0;chr7:0-158821424:0;chr8:0-146274826:0;chr9:0-140273252:0;chrX:0-154913754:0;chrY:0-57772954:0 AC005351;AC005592;AC005609;AC005618;AC007638;AC008383;AC008412;AC008514;AC008565.1;AC008671;AC008676;AC008781;AC010296;AC010468;AC011406;AC025165;AC034205;AC034207;AC034236;AC073366;AC078983;AC083805;AC112165;AC124890;AC127894.1;AC139931.1;ACSL6;ADAMTS19;AGAP2;AL022344;AL031601;ANKFN1;ANTXRL;APC;AQPEP;ARGFXP1;ARHGAP22;ARHGAP26;ARHGAP9;ATP6V0E1;AVIL;B4GALNT1;BEST3;BMS1;BNIP1;C10ORF128;C10ORF136;C10ORF53;C10ORF71;C12ORF28;C12ORF56;C12ORF66;C17orf28;C20orf74;C5ORF50;C5ORF56;C5ORF58;CAMK4;CAND1;CCDC112;CCDC47;CCDC99;CCNI2;CCNYL2;CCT2;CCT5P1;CDH12;CDK4;CHAT;CHSY3;CNOT2;CNOT4;COL23A1;COMMD10;CPM;CPSF6;CREBRF;CSF1R;CSGALNACT2;CTB-118N6.3;CTB-131B5.2;CTB-138E5.1;CTB-13H5.1;CTB-161M19.1;CTB-161M19.2;CTB-174D11.1;CTB-174D11.2;CTB-1H10.1;CTB-1I21.2;CTB-3M24.3;CTB-46E9.1;CTB-70D19.1;CTB-73N10.1;CTB-78O21.1;CTB-85P21.1;CTB-88F18.2;CTB-88F18.3;CTC-210G5.1;CTC-276P9.2;CTC-287O8.1;CTC-313D10.1;CTC-329H14.1;CTC-339D2.1;CTC-339F2.2;CTC-342P15.1;CTC-362D12.1;CTC-426B10.1;CTC-428G20.1;CTC-428G20.2;CTC-428G20.5;CTC-428G20.6;CTC-441N14.1;CTC-441N14.2;CTC-441N14.4;CTC-448D22.1;CTC-459M5.1;CTC-459M5.2;CTC-499J9.1;CTC-504A5.1;CTC-507E12.1;CTC-546K23.1;CTC-551A13.1;CTC-555I19.1;CTC-575N7.1;CTC-806A22.1;CTD-2020P22.1;CTD-2089O24.1;CTD-2089O24.2;CTD-2158P22.1;CTD-2195M15.1;CTD-2197I11.1;CTD-2201G3.1;CTD-2281M20.1;CTD-2287O16.1;CTD-2287O16.2;CTD-2334D19.1;CTD-2410N18.1;CTD-2544H17.1;CTD-2587M2.1;CTD-2613O8.1;CTD-3179P9.1;CTD-3179P9.2;CTDSP2;CXCL12;CYFIP2;CYP27B1;DCTN2;DDIT3;DLX3;DLX4;DOCK2;DRGX;DTX3;DUSP1;DYRK2;EFCAB9;EIF3LP2;EIF4EBP3;EPB41L4A;EPB41L4A-AS1;ERCC6;ERGIC1;FAM170B;FAM196B;FAM19A2;FBLL1;FBXL21;FBXO38;FBXW11;FEM1C;FER;FGF18;FNDC9;FNIP1;FOXI1;FRMPD2;FRS2;GABRA1;GABRP;GDF10;GDF2;GLI1;GNS;GPR151;GPR182;GPRIN2;GRAMD3;GRIP1;GRXCR2;GS1-410F4.1;H2AFY;HARS2;HINT1;HLF;HMGXB3;HMHB1;HNRNPA0;HSPD1P18;IFNG;IL12B;IL22;IL26;IL9;INHBC;INHBE;ISOC1;KCNIP1;KCNMB1;KCNMB4;KCNN2;KCTD16;KIF5A;KRT18P42;KRT8P22;LCP2;LEMD3;LOC100505678;LOX;LRP1;LRRC10;LSM11;LYZ;MAN2A1;MAPK8;MARS;MBD6;MCC;MDM1;MDM2;MEGF10;METTL1;METTL21B;MIR1228;MIR218-2;MIR26A2;MIR584;MIR585;MIR616;MMD;MRC2;MRPS5P3;MSMB;MUCL1;MYO1A;NCOA4;NDUFA4L2;NEURL1B;NEUROD4;NKX2-5;NPM1;NREP;NUP107;NXPH4;OGDHL;OR10U1P;OR6C1;OR6C2;OR6C5P;OR6C65;OR6C66P;OR6C69P;OR6C70;OR6C71P;OR6C74;OS9;P4HA2;PANK3;PCDHB16;PCDHB18;PCDHB5;PCDHGA1;PCDHGA12;PCDHGB8P;PCDHGC3;PCTP;PGBD3;PGGT1B;PIP4K2C;PLAC8L1;PPM1H;PPP2R2B;PPYR1;PRELID2;PRR16;PRRC1;R3HDM2;RAB3IP;RANBP17;RAP1B;RAPGEF6;RASGEF1A;RASSF3;RASSF4;RBP3;RDH16;RET;RNF145;RNU7-34P;RP1-45I14.1;RP11-1094H24.3;RP11-109G10.2;RP11-114H21.2;RP11-114H7.1;RP11-114H7.2;RP11-114H7.3;RP11-118M9.3;RP11-119J18.1;RP11-120B7.1;RP11-123B3.2;RP11-124O11.1;RP11-124O11.2;RP11-13E1.3;RP11-159A18.1;RP11-159K7.2;RP11-164D18.2;RP11-168P8.3;RP11-168P8.4;RP11-168P8.7;RP11-178A10.1;RP11-20J15.2;RP11-20J15.3;RP11-231G15.1;RP11-231G15.2;RP11-231G15.3;RP11-249M12.2;RP11-254B13.1;RP11-255M1.1;RP11-256K7.1;RP11-272J7.1;RP11-272J7.4;RP11-278J6.3;RP11-292F22.3;RP11-292F22.4;RP11-292F22.6;RP11-2N5.2;RP11-304F15.5;RP11-313J2.1;RP11-314P12.2;RP11-314P12.3;RP11-346A9.1;RP11-371M22.1;RP11-381K20.4;RP11-38L15.3;RP11-402L1.12;RP11-402L1.4;RP11-438C19.1;RP11-438C19.2;RP11-463P17.1;RP11-463P17.3;RP11-481A12.2;RP11-492A10.1;RP11-492L8.2;RP11-507K13.4;RP11-507K13.6;RP11-507P23.3;RP11-510I6.3;RP11-512N4.2;RP11-515C16.7;RP11-517I3.1;RP11-523O18.1;RP11-523O18.5;RP11-534L6.2;RP11-534L6.5;RP11-535A15.1;RP11-541M12.3;RP11-541M12.5;RP11-542E6.3;RP11-56A21.4;RP11-571M6.1;RP11-637A17.1;RP11-733D4.1;RP11-74D3.2;RPL26L1;RPS17P2;SCPEP1;SDR9C7;SEMA6A;SGMS1;SH3PXD2B;SH3RF2;SHMT2;SLC16A7;SLC18A3;SLC25A48;SLC26A10;SLC35A4;SLC35E3;SLIT3;SMAD5-AS1;SNCAIP;SNORA13;SNORA70G;SNORA74A;SNORA74B;SPINK5;SRFBP1;SRGAP1;SRP19;STAC3;STARD4;STAT6;STC2;STK10;SYT15;TAC3;TAF7;TCERG1L;TESPA1;TGFBI;TIGD6;TLX3;TMEM100;TMEM194A;TMEM232;TNFAIP8;TNIP1;TRIM36;TSFM;TSLP;TSPAN31;TSSK1B;TTYH2;UBTD2;VSTM4;VTRNA1-1;VTRNA1-2;WDR36;WFDC13;WWC1;XXYAC-YR14BB7.1;YEATS4;YIPF5;YTHDC2;ZBTB39;ZFAND4;ZNF300;ZNF32-AS3;ZNF37BP;ZNF474;ZNF488; Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA We report the results of whole-genome and transcriptome sequencing of tumor and adjacent normal tissue samples from 17 patients with non-small cell lung carcinoma (NSCLC). We identified 3,726 point mutations and more than 90 indels in the coding sequence, with an average mutation frequency more than 10-fold higher in smokers than in never-smokers. Novel alterations in genes involved in chromatin modification and DNA repair pathways were identified, along with DACH1, CFTR, RELN, ABCB5, and HGF. Deep digital sequencing revealed diverse clonality patterns in both never-smokers and smokers. All validated EFGR and KRAS mutations were present in the founder clones, suggesting possible roles in cancer initiation. Analysis revealed 14 fusions, including ROS1 and ALK, as well as novel metabolic enzymes. Cell-cycle and JAK-STAT pathways are significantly altered in lung cancer, along with perturbations in 54 genes that are potentially targetable with currently available drugs. NCBI 36/hg18 Yes CDH12,C17orf28;COL23A1,PPM1H;FAM19A2,ANKFN1;FRS2,KCNMB4;RASSF3,TTYH2;SGMS1,STK10;TNIP1,GRIP1 CTDB0272 Research 23622249 Baca SC, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, Van Allen E, Kryukov GV, Sboner A, Theurillat JP, Soong TD, Nickerson E, Auclair D, Tewari A, Beltran H, Onofrio RC, Boysen G, Guiducci C, Barbieri CE, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Ramos AH, Winckler W, Cipicchio M, Ardlie K, Kantoff PW, Berger MF, Gabriel SB, Golub TR, Meyerson M, Lander ES, Elemento O, Getz G, Demichelis F, Rubin MA, Garraway LA Punctuated evolution of prostate cancer genomes Cell 2013 Apr 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,X Prostate cancer Next Generation Sequencing Homo sapiens PR-4240 Illumina GAIIx chr10:0-28798643:0;chr10:102722863-102737336:1;chr10:102737337-106933125:0;chr10:106933126-106936751:-1;chr10:106936752-135534747:0;chr10:28798644-28823111:1;chr10:28823112-55881658:0;chr10:55881659-55886559:1;chr10:55886560-63363113:0;chr10:63363114-63364882:1;chr10:63364883-65240015:0;chr10:65240016-65246750:1;chr10:65246751-69241230:0;chr10:69241231-69251184:1;chr10:69251185-70288347:0;chr10:70288348-70408992:1;chr10:70359688-70366097:-1;chr10:70408993-102722862:0;chr11:0-17954936:0;chr11:102260304-102409002:1;chr11:102409003-105587608:0;chr11:105587609-105605438:1;chr11:105605439-118465634:0;chr11:118465635-118477498:1;chr11:118477499-118495063:0;chr11:118495064-118504600:1;chr11:118504601-131260484:0;chr11:131260485-131295986:-1;chr11:131295987-135006516:0;chr11:17954937-17987804:1;chr11:17987805-32724555:0;chr11:32724556-32734209:1;chr11:32734210-42534109:0;chr11:42534110-42860112:-1;chr11:42860113-48102613:0;chr11:48102614-48119738:1;chr11:48119739-63210201:0;chr11:63210202-63220045:1;chr11:63220046-65203827:0;chr11:65203828-65343417:1;chr11:65343418-77073938:0;chr11:77073939-77079966:1;chr11:77079967-86171160:0;chr11:86171161-86179813:1;chr11:86179814-86429780:0;chr11:86429781-86927601:1;chr11:86927602-102260303:0;chr12:0-6677239:0;chr12:10735123-11269684:1;chr12:112541509-112577557:1;chr12:112577558-133851895:0;chr12:11269685-14912085:0;chr12:14912086-14914864:1;chr12:14914865-50374409:0;chr12:50374410-50379348:1;chr12:50379349-56745652:0;chr12:56745653-56757419:1;chr12:56757420-88344345:0;chr12:6677240-6684905:1;chr12:6684906-9482514:0;chr12:88344346-88346948:1;chr12:88344891-88346347:-1;chr12:88346949-89606641:0;chr12:89606642-89609186:1;chr12:89609187-93215462:0;chr12:93215463-93274177:1;chr12:93274178-112541508:0;chr12:9482515-9548750:1;chr12:9548751-10735122:0;chr13:0-39271853:0;chr13:39271854-39273944:-1;chr13:39273945-70068430:0;chr13:70068431-70072023:1;chr13:70072024-73246743:0;chr13:73246744-73253336:1;chr13:73253337-115169878:0;chr14:0-26459524:0;chr14:26459525-26467320:1;chr14:26467321-32939877:0;chr14:32939878-33497530:-1;chr14:33497531-35260643:0;chr14:35260644-35288629:1;chr14:35288630-46044108:0;chr14:46044109-46047637:1;chr14:46047638-52160195:0;chr14:52160196-52167266:1;chr14:52167267-52181440:0;chr14:52181441-52187039:1;chr14:52187040-76585116:0;chr14:76585117-76598512:1;chr14:76598513-107349540:0;chr15:0-40822288:0;chr15:40822289-40832103:1;chr15:40832104-42923235:0;chr15:42923236-42929223:1;chr15:42929224-73571036:0;chr15:73571037-73681329:1;chr15:73681330-75473432:0;chr15:75473433-75480613:1;chr15:75480614-91047360:0;chr15:91047361-91124244:1;chr15:91124245-102531392:0;chr16:0-12401591:0;chr16:12401592-12407076:1;chr16:12407077-16062671:0;chr16:16062672-16104473:1;chr16:16104474-17615991:0;chr16:17615992-17618492:1;chr16:17618493-19156719:0;chr16:19156720-19158367:1;chr16:19158368-21143805:0;chr16:21143806-21148639:1;chr16:21148640-24465875:0;chr16:24465876-24468644:1;chr16:24468645-28497791:0;chr16:28497792-28538203:1;chr16:28538204-30377516:0;chr16:30377517-30384222:1;chr16:30384223-56414071:0;chr16:56414072-56436959:1;chr16:56436960-85845381:0;chr16:85845382-85855169:1;chr16:85855170-90354753:0;chr17:0-5292302:0;chr17:39311912-39317124:1;chr17:39317125-41329265:0;chr17:41329266-41339427:1;chr17:41339428-41499642:0;chr17:41499643-41687452:-1;chr17:41687453-58660383:0;chr17:5292303-5337868:1;chr17:5337869-39311911:0;chr17:58660384-58694376:1;chr17:58694377-62577177:0;chr17:62577178-62582539:-1;chr17:62582540-62631359:0;chr17:62631360-62757660:1;chr17:62757661-67976370:0;chr17:67976371-67980506:1;chr17:67980507-74199866:0;chr17:74199867-74236393:1;chr17:74236394-81195210:0;chr18:0-11383768:0;chr18:11383769-11389185:1;chr18:11389186-41864324:0;chr18:41864325-41871049:1;chr18:41871050-60844964:0;chr18:60844965-60850016:1;chr18:60850017-74140392:0;chr18:74140393-74766252:1;chr18:74766253-78077248:0;chr19:0-2319828:0;chr19:10145402-10153126:1;chr19:10153127-11722008:0;chr19:11722009-11726490:1;chr19:11726491-49234042:0;chr19:2319829-2329010:1;chr19:2329011-10145401:0;chr19:49234043-49243701:1;chr19:49243702-52480245:0;chr19:52480246-52493543:1;chr19:52493544-59128983:0;chr1:0-82168832:0;chr1:145024869-145027345:-1;chr1:145027346-145291469:0;chr1:145291470-145831623:-1;chr1:145831624-151836088:0;chr1:151836089-151842495:1;chr1:151842496-161797265:0;chr1:161797266-161803081:1;chr1:161803082-169186504:0;chr1:169186505-169193116:1;chr1:169193117-178422707:0;chr1:178422708-178430707:1;chr1:178430708-190592563:0;chr1:190592564-190629344:1;chr1:190629345-219315749:0;chr1:219315750-219356847:1;chr1:219356848-220752856:0;chr1:220752857-220755619:-1;chr1:220755620-224402792:0;chr1:224402793-224492679:1;chr1:224492680-231997597:0;chr1:231997598-232007006:1;chr1:232007007-236477646:0;chr1:236477647-236620712:1;chr1:236620713-245289679:0;chr1:245289680-245295807:-1;chr1:245295808-249250621:0;chr1:82168833-82198679:-1;chr1:82198680-145024868:0;chr20:0-1507751:0;chr20:1507752-1523770:1;chr20:1523771-3210173:0;chr20:3210174-3253940:1;chr20:3253941-8985445:0;chr20:33510642-33564651:1;chr20:33564652-55298590:0;chr20:55298591-55358674:1;chr20:55358675-63025520:0;chr20:8985446-8991551:1;chr20:8991552-33510641:0;chr21:0-17860811:0;chr21:17860812-17864934:1;chr21:17864935-32303636:0;chr21:32303637-32310999:1;chr21:32311000-48129895:0;chr22:0-22264335:0;chr22:22264336-22266539:1;chr22:22266540-31499570:0;chr22:31499571-31511652:1;chr22:31511653-35262710:0;chr22:35262711-35419762:-1;chr22:35419763-46193460:0;chr22:46193461-46202686:1;chr22:46202687-51304566:0;chr2:0-10436904:0;chr2:10436905-10447185:1;chr2:10447186-81289323:0;chr2:132888749-132893452:1;chr2:132893453-169880759:0;chr2:169880760-169890777:1;chr2:169890778-170941058:0;chr2:170941059-170962808:1;chr2:170962809-178588472:0;chr2:178588473-178589599:-1;chr2:178589600-178659298:0;chr2:178659299-178664226:1;chr2:178664227-243199373:0;chr2:81289324-81291625:1;chr2:81291626-132888748:0;chr3:0-24470243:0;chr3:108500541-108508091:1;chr3:108508092-116735192:0;chr3:116735193-116898178:-1;chr3:116898179-129522146:0;chr3:129522147-129533108:1;chr3:129533109-155867847:0;chr3:155867848-155870926:1;chr3:155870927-158166588:0;chr3:158166589-158177389:1;chr3:158177390-159969133:0;chr3:159969134-160033726:1;chr3:160033727-177903502:0;chr3:177903503-177905697:1;chr3:177905698-187772343:0;chr3:187772344-187773413:-1;chr3:187773414-197552792:0;chr3:197552793-197556780:1;chr3:197556781-198022430:0;chr3:24470244-24479833:1;chr3:24479834-108500540:0;chr4:0-28787982:0;chr4:103175819-103239170:1;chr4:103239171-119006042:0;chr4:119006043-119011703:1;chr4:119011704-140099015:0;chr4:140099016-140110741:1;chr4:140110742-156685149:0;chr4:156685150-156692101:1;chr4:156692102-159540778:0;chr4:159540779-159544933:1;chr4:159544934-174070993:0;chr4:174070994-174073976:1;chr4:174073977-191154276:0;chr4:28787983-28793146:1;chr4:28793147-33552889:0;chr4:33552890-33588004:-1;chr4:33588005-43030994:0;chr4:43030995-43043941:1;chr4:43043942-67277109:0;chr4:67277110-67283376:1;chr4:67283377-71749634:0;chr4:71749635-71770777:1;chr4:71770778-72234416:0;chr4:72234417-72251351:1;chr4:72251352-73236017:0;chr4:73236018-73239851:1;chr4:73239852-98210744:0;chr4:98210745-98393227:-1;chr4:98393228-103175818:0;chr5:0-39766548:0;chr5:139108508-139118099:1;chr5:139118100-147227125:0;chr5:147227126-147238008:1;chr5:147238009-150028069:0;chr5:150028070-150034288:1;chr5:150034289-153604644:0;chr5:153604645-153611993:1;chr5:153611994-165031274:0;chr5:165031275-165367931:1;chr5:165367932-166179459:0;chr5:166179460-166437661:-1;chr5:166437662-180915260:0;chr5:39766549-39797506:1;chr5:39797507-64263305:0;chr5:64263306-64267978:1;chr5:64267979-64547788:0;chr5:64547789-64561130:1;chr5:64561131-66502894:0;chr5:66502895-66513592:1;chr5:66513593-73878834:0;chr5:73878835-73886980:1;chr5:73886981-95659734:0;chr5:95659735-96423586:1;chr5:96423587-139108507:0;chr6:0-15773545:0;chr6:139999672-140011183:-1;chr6:140011184-151330809:0;chr6:151330810-151334496:1;chr6:151334497-171115067:0;chr6:15773546-15781944:1;chr6:15781945-21942097:0;chr6:21942098-21954339:1;chr6:21954340-25622926:0;chr6:25622927-25624819:-1;chr6:25624820-36452966:0;chr6:36452967-36581926:1;chr6:36581927-55439314:0;chr6:55439315-55444190:1;chr6:55444191-83490424:0;chr6:83490425-83506705:1;chr6:83506706-139999671:0;chr7:0-18301975:0;chr7:105065039-106046446:1;chr7:106046447-138565111:0;chr7:138565112-138568884:1;chr7:138568885-140315580:0;chr7:140315581-140336841:1;chr7:140336842-150043403:0;chr7:150043404-150096341:1;chr7:150096342-159138663:0;chr7:18301976-18306938:1;chr7:18306939-26538121:0;chr7:26538122-26540184:1;chr7:26540185-32907006:0;chr7:32907007-32916475:1;chr7:32916476-33495046:0;chr7:33495047-33542382:-1;chr7:33542383-39777457:0;chr7:39777458-39781587:1;chr7:39781588-69563268:0;chr7:69563269-69585150:1;chr7:69585151-105065038:0;chr8:0-17373890:0;chr8:124313715-124343313:1;chr8:124343314-127700635:0;chr8:127700636-127704718:1;chr8:127704719-146364022:0;chr8:17373891-17390217:1;chr8:17390218-42990313:0;chr8:42990314-42997428:1;chr8:42997429-81573573:0;chr8:81573574-81575226:1;chr8:81575227-83424551:0;chr8:83424552-83432366:1;chr8:83432367-83636165:0;chr8:83636166-83639412:1;chr8:83639413-124313714:0;chr9:0-6854649:0;chr9:112051842-112058473:1;chr9:112058474-123547631:0;chr9:123547632-123553535:1;chr9:123553536-130865956:0;chr9:130865957-130881858:1;chr9:130881859-135303405:0;chr9:135303406-135311277:1;chr9:135311278-141213431:0;chr9:36188184-36191944:1;chr9:36191945-38614579:0;chr9:38614580-38619363:1;chr9:38619364-79943049:0;chr9:6854650-6859725:1;chr9:6859726-9081530:0;chr9:79943050-79949736:1;chr9:79949737-88924638:0;chr9:88924639-88928909:1;chr9:88928910-91610056:0;chr9:9081531-9723906:1;chr9:91610057-91612334:1;chr9:91612335-112051841:0;chr9:9723907-36188183:0;chrX:0-9346637:0;chrX:105110822-105114362:1;chrX:105114363-115573788:0;chrX:115573789-115579309:1;chrX:115579310-155270560:0;chrX:29834551-30289625:1;chrX:30289626-67552622:0;chrX:67552623-68462230:1;chrX:68462231-105110821:0;chrX:9346638-9350215:1;chrX:9350216-29834550:0;chrY:0-59373566:0 hs4:163146895-163146895,hs10:61261509-61261509;hs7:129376256-129376256,hs7:140488296-140488296;hs1:89045325-89045325,hs1:98503700-98503700;hs4:108786689-108786689,hs6:34507314-34507314;hs8:101571335-101571335,hs8:134251631-134251631;hs1:37895793-37895793,hs14:69898364-69898364;hs8:101571243-101571243,hs8:134282017-134282017;hs2:216250695-216250695,hs17:40026334-40026334;hs6:25868628-25868628,hs6:25870676-25870676;hs17:28603208-28603208,hs17:33312452-33312452;hs6:52911026-52911026,hs6:108854713-108854713;hs17:28621653-28621653,hs17:34042274-34042274;hs1:146714469-146714469,hs1:227145449-227145449;hs4:108766298-108766298,hs6:34196330-34196330;hs8:21194022-21194022,hs8:28600647-28600647;hs1:50043135-50043135,hs10:121268308-121268308;hs17:28615526-28615526,hs17:33444740-33444740;hs17:28407224-28407224,hs17:33904149-33904149;hs17:34437724-34437724,hs17:41689797-41689797;hs17:35329550-35329550,hs17:41293020-41293020;hs21:36011737-36011737,hs21:37140196-37140196;hs17:28705429-28705429,hs17:34014812-34014812;hs1:224208185-224208185,hs3:49759952-49759952;hs6:7490619-7490619,hs11:12224636-12224636;hs11:32766540-32766540,hs19:41911483-41911483;hs13:30508208-30508208,hs13:106399572-106399572;hs6:52910988-52910988,hs21:19762992-19762992;hs5:96423590-96423590,hs14:27398939-27398939;hs6:1592492-1592492,hs7:38343884-38343884;hs2:216250713-216250713,hs17:40020749-40020749;hs11:107594444-107594444,hs11:113731568-113731568;hs14:31956000-31956000,hs14:31962838-31962838;hs14:45474473-45474473,hs14:55583512-55583512;hs17:40588270-40588270,hs17:40810696-40810696;hs2:211069026-211069026,hs6:144796696-144796696;hs7:33480577-33480577,hs17:17569822-17569822;hs11:107631867-107631867,hs11:113742286-113742286;hs6:108857912-108857912,hs21:19763098-19763098;hs10:89685131-89685131,hs10:94184874-94184874;hs1:50043182-50043182,hs10:121210181-121210181;hs6:122530852-122530852,hs6:144796705-144796705;hs7:30849670-30849670,hs7:41076206-41076206;hs6:13715127-13715127,hs7:83126832-83126832;hs8:98439687-98439687,hs15:70442102-70442102;hs14:36636347-36636347,hs14:38060026-38060026;hs6:142266070-142266070,hs9:126996654-126996654;hs8:38182477-38182477,hs8:38190587-38190587;hs1:50254546-50254546,hs1:117114854-117114854;hs8:80669296-80669296,hs20:46041131-46041131;hs15:79603271-79603271,hs17:35325032-35325032;hs8:98439385-98439385,hs15:70433298-70433298;hs1:225243298-225243298,hs21:45608728-45608728;hs2:69230635-69230635,hs4:72249505-72249505;hs7:129376393-129376393,hs7:140487359-140487359;hs1:230848624-230848624,hs3:195366948-195366948;hs2:69142378-69142378,hs4:72064134-72064134;hs1:60194134-60194134,hs7:130834535-130834535;hs2:133587761-133587761,hs10:4998009-4998009;hs6:13269761-13269761,hs7:83126631-83126631;hs8:80644023-80644023,hs8:80645939-80645939;hs12:110849450-110849450,hs22:22867853-22867853;hs17:27757604-27757604,hs17:29976768-29976768;hs1:195971344-195971344,hs1:211688992-211688992;hs2:25087680-25087680,hs13:43935436-43935436;hs5:132817374-132817374,hs10:121764221-121764221;hs6:7487455-7487455,hs11:12229866-12229866;hs17:28426421-28426421,hs17:41690948-41690948;hs1:116080465-116080465,hs10:121800725-121800725;hs5:95659738-95659738,hs14:27398753-27398753;hs8:80225170-80225170,hs20:46210469-46210469;hs17:34065891-34065891,hs17:38430026-38430026;hs1:58723765-58723765,hs1:99307642-99307642;hs1:115889872-115889872,hs10:121805645-121805645;hs6:145125250-145125250,hs6:149631433-149631433;hs12:70186432-70186432,hs12:70205596-70205596;hs5:180666036-180666036,hs12:93274170-93274170;hs7:65363392-65363392,hs14:58944288-58944288;hs7:65369779-65369779,hs14:58944060-58944060;hs8:80139356-80139356,hs8:80240362-80240362;hs15:79603313-79603313,hs17:35329550-35329550;hs17:25642769-25642769,hs17:41540473-41540473;hs1:80428824-80428824,hs1:81951307-81951307;hs2:207345660-207345660,hs2:209749871-209749871;hs3:24479619-24479619,hs5:171848056-171848056;hs3:24479821-24479821,hs5:171876575-171876575;hs5:96550555-96550555,hs14:70087721-70087721;hs8:79596689-79596689,hs8:80073822-80073822;hs1:60194304-60194304,hs7:130827760-130827760;hs1:59661848-59661848,hs10:121805060-121805060;hs6:145048115-145048115,hs6:149539201-149539201;hs9:104781660-104781660,hs9:115054783-115054783;hs15:62654675-62654675,hs22:23369049-23369049;hs1:102924330-102924330,hs6:16889018-16889018;hs1:50258532-50258532,hs10:126276843-126276843;hs4:1790364-1790364,hs12:103842497-103842497;hs6:155682610-155682610,hs11:57728272-57728272;hs6:155691882-155691882,hs11:57728252-57728252;hs8:80073583-80073583,hs8:80645177-80645177;hs9:104787881-104787881,hs11:68416467-68416467;hs10:89674974-89674974,hs10:94144259-94144259;hs14:33651065-33651065,hs17:38407629-38407629;hs1:55676507-55676507,hs11:65206603-65206603;hs1:55686591-55686591,hs11:65206384-65206384;hs4:72409958-72409958,hs17:41704165-41704165;hs6:107850931-107850931,hs22:23271140-23271140;hs8:34268210-34268210,hs17:17621466-17621466;hs17:28234791-28234791,hs17:28504265-28504265;hs1:53934406-53934406,hs10:121839093-121839093;hs2:3028194-3028194,hs2:5405183-5405183;hs3:95603862-95603862,hs20:43877450-43877450;hs4:38707775-38707775,hs6:16451138-16451138;hs4:72349157-72349157,hs9:68458031-68458031;hs5:174735682-174735682,hs17:37706997-37706997;hs17:35875710-35875710,hs17:39725909-39725909;hs1:65265150-65265150,hs3:169164605-169164605;hs1:65270801-65270801,hs3:169739027-169739027;hs2:25064638-25064638,hs17:45460714-45460714;hs3:79123742-79123742,hs5:98699524-98699524;hs3:79123778-79123778,hs5:98699838-98699838;hs3:68750411-68750411,hs11:102260307-102260307;hs6:57321666-57321666,hs6:75597990-75597990;hs17:35875727-35875727,hs17:39726419-39726419;hs17:43283417-43283417,hs17:45438048-45438048;hs1:117114140-117114140,hs10:126563867-126563867;hs3:67814589-67814589,hs3:74269927-74269927;hs3:188344787-188344787,hs7:106905327-106905327;hs3:70854854-70854854,hs13:29208573-29208573;hs16:23860010-23860010,hsX:53648872-53648872 AATF;ACADL;ACLY;ACSS2;ADAM23;ADAMTS3;ADAMTS6;ADCY3;AGBL4;AGT;AKAP6;AMFR;ANKRD18A;ANKRD46;AP2B1;APOF;ARCN1;ATAD2;ATF6;ATXN1;ATXN10;AUTS2;BAZ1A;BBS9;BCKDHA;BCL2;BLMH;BRAF;C12orf42;C17orf57;C1QBP;C20orf194;C21orf34;C3P1;C9orf171;C9orf47;CABC1;CCDC55;CCDC73;CD58;CHD1L;CHD4;CLN3;CLTA;COG5;CPD;CRTC3;CTNNA3;CWC27;DISC1;DNAH14;DNAH3;EDARADD;EEA1;EFCAB5;EHBP1L1;ENOX1;EPB41L4B;EXTL3;FAM164A;FAM178A;FAM179B;FAM188B;FBXW2;FGGY;FLJ22536;FN1;FOXA1;FREM2;FRMD6;FSTL4;GALNT10;GMPPB;GNB2L1;GRIA4;GRK5;GRXCR1;GUCY1B3;HGSNAT;HMGCLL1;HPCAL1;HUWE1;ICK;IFT80;IL1RAPL1;KBTBD2;KCNAB1;KCTD20;KDM4C;KIAA0247;KIAA0586;KIAA1549;KLHL11;KRT9;KRTAP4;LHPP;LIG3;LOC100289019;LPP;LRCH3;LYPLAL1;MARK1;MBP;ME3;MECOM;MICAL2;MKLN1;MOBKL1A;MTHFD1L;MYH7B;MYLPF;NAA25;NBPF10;NBR1;NBR2;NCKAP5;NCOA3;NCRNA00265;NDRG1;NDST3;NEO1;NME7;NOP2;NPAS3;NRF1;NRK;NTM;NUP88;NVL;OPHN1;PAK1;PCDH15;PDE11A;PDE4DIP;PEX12;PHACTR1;PHLDB1;PPM1D;PRIM2;PRKCB;PTEN;PTPRD;PTPRJ;RAB3IP;RAD51L3;RAI1;RASAL2;RASIP1;RASL10B;RAVER2;RGS10;RNF157;ROBO1;ROD1;RSRC1;RXFP1;S1PR3;SEMA3E;SEMA4G;SERGEF;SGMS2;SH3PXD2B;SIRPD;SLC17A3;SLC25A16;SLC25A25;SLC39A8;SLC39A9;SLC4A11;SLC4A4;SLC6A14;SLC7A2;SMTN;SMURF2;SNX29;SOBP;SORCS3;SPDEF;SPPL2B;SSH2;STARD9;STAT2;SYNPO;TAOK1;TBC1D10B;TET1;THRB;TMCC1;TMED3;TMEM135;TMPRSS15;TRAFD1;TUBG2;USP24;USP28;UTRN;VKORC1L1;VPS13A;WAC;WHSC1L1;WIPF2;ZCCHC6;ZNF350;ZNF516;ZNF627;ZNF704; Harvard Medical School, Boston, MA 02115, USA The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term chromoplexy, frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. GRCh37/hg19 phs000447 Yes AATF,NBR2;ACADL,UTRN;ACSS2,MYH7B;ADCY3,C17orf57;ADCY3,ENOX1;AGBL4,CD58;AGBL4,GRK5;AGBL4,LHPP;AGBL4,RGS10;AKAP6,NPAS3;ANKRD46,NDRG1;ARCN1,PHLDB1;BLMH,AP2B1;BLMH,LIG3;BLMH,RAD51L3;C9orf47,S1PR3;CCDC73,BCKDHA;CHD1L,CABC1;CPD,AP2B1;EFCAB5,PEX12;FAM178A,SEMA4G;FGGY,MKLN1;FN1,ACLY;FN1,KLHL11;GNB2L1,EEA1;ICK,TMPRSS15;LPP,COG5;NAA25,TRAFD1;NOP2,CHD4;NPAS3,WIPF2;NRF1,BRAF;NUP88,C1QBP;PHACTR1,SEMA3E;PRKCB,HUWE1;RASL10B,WIPF2;RAVER2,MECOM;SGMS2,SPDEF;SLC25A16,TET1;SLC25A25,LOC100289019;SLC4A11,C20orf194;SMURF2,LOC146880;SSH2,CCDC55;STAT2,APOF;SYNRG,KRT9;TBC1D10B,MYLPF;THRB,SH3PXD2B;TMED3,AATF;VKORC1L1,KIAA0586;ZNF516,MBP CTDB0273 Research 23622249 Baca SC, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, Van Allen E, Kryukov GV, Sboner A, Theurillat JP, Soong TD, Nickerson E, Auclair D, Tewari A, Beltran H, Onofrio RC, Boysen G, Guiducci C, Barbieri CE, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Ramos AH, Winckler W, Cipicchio M, Ardlie K, Kantoff PW, Berger MF, Gabriel SB, Golub TR, Meyerson M, Lander ES, Elemento O, Getz G, Demichelis F, Rubin MA, Garraway LA Punctuated evolution of prostate cancer genomes Cell 2013 Apr 1,2,3,4,5,6,7,8,9,11,13,14,15,X Prostate cancer Next Generation Sequencing Homo sapiens PR-02-1431 Illumina GAIIx chr10:0-67545254:0;chr10:129455829-129459318:-1;chr10:129459319-135534747:0;chr10:67545255-67549814:-1;chr10:67549815-129455828:0;chr11:0-49250219:0;chr11:132575105-132615767:-1;chr11:132615768-135006516:0;chr11:49250220-49287712:-1;chr11:49287713-132575104:0;chr12:0-133851895:0;chr13:0-85392661:0;chr13:108217365-108250572:-1;chr13:108250573-115169878:0;chr13:85392662-86207104:-1;chr13:86207105-108217364:0;chr14:0-107349540:0;chr15:0-52861486:0;chr15:52861487-53659730:1;chr15:53659731-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-241965993:0;chr1:241965994-241995938:-1;chr1:241995939-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-52498618:0;chr2:104789047-104797265:-1;chr2:104797266-126969343:0;chr2:126969344-127756885:-1;chr2:127756886-142833158:0;chr2:142833159-142847882:-1;chr2:142847883-155270304:0;chr2:155270305-155281646:-1;chr2:155281647-197657982:0;chr2:197657983-197683092:-1;chr2:197683093-198242393:0;chr2:198242394-198244545:-1;chr2:198244546-243199373:0;chr2:52498619-52501611:-1;chr2:52501612-59078160:0;chr2:59078161-59149061:-1;chr2:59149062-77766624:0;chr2:77766625-77798281:-1;chr2:77798282-80644092:0;chr2:80644093-80646143:-1;chr2:80646144-104789046:0;chr3:0-85952199:0;chr3:117935414-117954225:-1;chr3:117954226-160555652:0;chr3:160555653-160558994:-1;chr3:160558995-198022430:0;chr3:85952200-86114743:-1;chr3:86114744-90208845:0;chr3:90208846-90235690:-1;chr3:90235691-117935413:0;chr4:0-94349975:0;chr4:134550464-135258385:-1;chr4:135258386-191154276:0;chr4:94349976-94351912:-1;chr4:94351913-94539030:0;chr4:94539031-95167855:-1;chr4:95167856-134550463:0;chr5:0-18641232:0;chr5:18641233-19329676:-1;chr5:19012943-19343598:1;chr5:19343599-94041031:0;chr5:94041032-94498258:1;chr5:94498259-180915260:0;chr6:0-5070180:0;chr6:101260703-101263866:-1;chr6:101263867-103241132:0;chr6:103241133-103275724:-1;chr6:103275725-103302116:0;chr6:103302117-103333320:-1;chr6:103333321-122554530:0;chr6:122554531-122608457:-1;chr6:122608458-134438039:0;chr6:134438040-134459816:-1;chr6:134459817-171115067:0;chr6:5070181-5132765:-1;chr6:5132766-101260702:0;chr7:0-20433373:0;chr7:118809514-118883331:-1;chr7:118883332-119263653:0;chr7:119263654-119291227:-1;chr7:119291228-147385287:0;chr7:147385288-148101813:-1;chr7:148101814-152087761:0;chr7:152087762-152103550:-1;chr7:152103551-159138663:0;chr7:20433374-20441518:-1;chr7:20441519-41025413:0;chr7:41025414-41824223:-1;chr7:41824224-45995688:0;chr7:45995689-46071005:-1;chr7:46071006-46317388:0;chr7:46317389-46321362:-1;chr7:46321363-77772933:0;chr7:77772934-77776018:-1;chr7:77776019-83111113:0;chr7:83111114-83115293:-1;chr7:83115294-118809513:0;chr8:0-32129017:0;chr8:131671600-131697049:-1;chr8:131697050-132276884:0;chr8:132276885-132287641:-1;chr8:132287642-132746769:0;chr8:132746770-132750237:-1;chr8:132750238-136751739:0;chr8:136751740-137028417:-1;chr8:136927139-137293743:1;chr8:137293744-139077960:0;chr8:139077961-139641656:1;chr8:139641657-146364022:0;chr8:32129018-32135301:-1;chr8:32135302-50214898:0;chr8:50214899-51040240:1;chr8:50981269-51041041:-1;chr8:51041042-51508856:0;chr8:51508857-51531230:-1;chr8:51531231-55322070:0;chr8:55322071-55352467:-1;chr8:55352468-80858815:0;chr8:80858816-80860719:-1;chr8:80860720-85861245:0;chr8:85861246-85890883:-1;chr8:85890884-86912501:0;chr8:86912502-87003330:-1;chr8:87003331-87665849:0;chr8:87665850-87669585:-1;chr8:87669586-91825338:0;chr8:91825339-91830532:-1;chr8:91830533-131671599:0;chr9:0-4900731:0;chr9:30793045-30794774:-1;chr9:30794775-141213431:0;chr9:4900732-4995618:-1;chr9:4995619-6155342:0;chr9:6155343-6192058:-1;chr9:6192059-30793044:0;chrX:0-7414957:0;chrX:31395775-32195892:-1;chrX:32195893-78186096:0;chrX:7414958-8154831:1;chrX:78186097-78201384:-1;chrX:78201385-155270560:0;chrX:8154832-31395774:0;chrY:0-59373566:0 hs8:88444790-88444790,hs8:90229035-90229035;hs7:152103766-152103766,hs7:156644296-156644296;hs3:115157725-115157725,hsX:4019043-4019043;hs7:14785798-14785798,hs7:52411078-52411078;hs1:169439367-169439367,hs1:171045440-171045440;hs8:116041630-116041630,hs8:116171546-116171546;hs8:87873356-87873356,hs8:112670050-112670050;hs8:136557816-136557816,hs8:139692286-139692286;hs8:90238545-90238545,hs8:116061928-116061928;hs3:86105633-86105633,hs15:54383778-54383778;hsX:2449849-2449849,hsX:3137358-3137358;hs8:90092628-90092628,hs8:116850971-116850971;hs8:114040910-114040910,hs8:116175660-116175660;hs8:136592574-136592574,hs8:139572037-139572037;hs8:138882260-138882260,hs8:140974471-140974471;hs1:171045319-171045319,hs8:52284010-52284010;hs2:77610181-77610181,hs2:78170622-78170622;hs2:164326644-164326644,hs2:167606878-167606878;hs8:4025875-4025875,hs8:36625542-36625542;hs8:35993705-35993705,hs8:43527623-43527623;hs8:112754737-112754737,hs8:115726913-115726913;hs13:64460372-64460372,hs13:66472279-66472279;hs2:76145178-76145178,hs5:18457753-18457753;hs4:44915946-44915946,hs4:113127435-113127435;hs8:50216472-50216472,hs8:130558868-130558868;hs8:114013420-114013420,hs8:115721893-115721893;hs14:39923296-39923296,hs14:43107410-43107410;hsX:4930607-4930607,hsX:4938138-4938138;hs5:98256742-98256742,hs5:99280047-99280047;hs8:90133287-90133287,hs8:112671823-112671823;hs2:77674188-77674188,hs4:46290749-46290749;hs4:27979076-27979076,hs4:136740936-136740936;hs8:52264078-52264078,hs8:130582837-130582837;hs8:136877146-136877146,hs8:142113675-142113675;hs9:1670923-1670923,hs9:1695367-1695367;hs9:2632778-2632778,hs9:26963127-26963127;hs9:23582504-23582504,hs9:26955470-26955470;hs9:24777078-24777078,hs9:26371655-26371655;hs9:27729871-27729871,hs9:28470220-28470220;hs13:31061124-31061124,hs13:64135871-64135871;hs13:56750309-56750309,hs13:57607302-57607302;hs13:57669915-57669915,hs13:85630331-85630331;hs13:65778580-65778580,hs13:92113698-92113698;hsX:4976938-4976938,hsX:5391903-5391903;hs3:88081022-88081022,hs15:52791571-52791571;hs4:27745169-27745169,hs4:133627272-133627272;hs4:95127227-95127227,hs4:135195589-135195589;hs5:19361340-19361340,hs5:21625809-21625809;hs6:90869553-90869553,hs6:123731636-123731636;hs8:52539714-52539714,hs8:137790265-137790265;hs8:49137367-49137367,hs8:49431946-49431946;hs9:6690452-6690452,hs9:26943913-26943913;hs9:2052279-2052279,hs9:6746237-6746237;hs13:65786323-65786323,hs13:93273413-93273413;hs15:53829618-53829618,hs15:54258984-54258984;hsX:4945988-4945988,hsX:4979967-4979967;hs1:159921266-159921266,hs8:52631893-52631893;hs2:167589155-167589155,hs2:167694612-167694612;hs3:88050525-88050525,hs15:54295228-54295228;hs4:29546066-29546066,hs4:134418999-134418999;hs6:125444471-125444471,hs6:154207139-154207139;hs6:125896195-125896195,hs6:154255959-154255959;hs8:137859944-137859944,hs8:140069949-140069949;hs9:5914588-5914588,hs9:23433893-23433893;hs9:23455553-23455553,hs9:23980728-23980728;hs9:22020223-22020223,hs9:23970229-23970229;hs11:39325780-39325780,hs11:50618346-50618346;hs11:92475524-92475524,hs11:93298097-93298097;hs11:104221487-104221487,hs11:123210014-123210014;hs12:8403983-8403983,hs12:21911486-21911486;hs13:58385698-58385698,hs13:86444491-86444491;hsX:4936961-4936961,hsX:6215749-6215749;hsX:5110346-5110346,hsX:31416137-31416137;hs2:76166833-76166833,hs5:18551499-18551499;hs4:23169502-23169502,hs4:113629528-113629528;hs4:28910346-28910346,hs4:136631126-136631126;hs4:28986703-28986703,hs4:136641655-136641655;hs4:94545124-94545124,hs4:137852151-137852151;hs5:90731114-90731114,hs5:122080976-122080976;hs5:44910022-44910022,hs7:125256605-125256605;hs7:118850336-118850336,hs7:119110809-119110809;hs7:118883044-118883044,hs7:119107948-119107948;hs8:50217368-50217368,hs8:131711241-131711241;hs8:66501200-66501200,hs8:86999483-86999483;hs8:73988138-73988138,hs8:81321279-81321279;hs8:88431572-88431572,hs8:116853723-116853723;hs8:136978703-136978703,hs8:140080123-140080123;hs9:4770018-4770018,hs9:22331713-22331713;hs9:27753057-27753057,hs9:28490220-28490220;hs11:48339472-48339472,hs11:50619336-50619336;hs13:57920871-57920871,hs13:87070764-87070764;hs13:58599274-58599274,hs13:85644630-85644630;hs13:59098792-59098792,hs13:63893584-63893584;hs2:49765606-49765606,hs2:77167507-77167507;hs2:49998655-49998655,hs2:77574881-77574881;hs2:51225797-51225797,hs2:77181096-77181096;hs2:78282194-78282194,hs2:79844405-79844405;hs2:77667040-77667040,hs4:46286087-46286087;hs3:84440292-84440292,hs3:90204656-90204656;hs4:22870514-22870514,hs4:45779267-45779267;hs4:28092640-28092640,hs4:28355153-28355153;hs4:29570572-29570572,hs4:137160938-137160938;hs4:44913815-44913815,hs4:113136675-113136675;hs5:98257938-98257938,hs5:99283729-99283729;hs7:14795256-14795256,hs7:52401524-52401524;hs8:50205937-50205937,hs8:137867696-137867696;hs8:50454725-50454725,hs8:137076795-137076795;hs8:67409910-67409910,hs8:86926799-86926799;hs8:136924749-136924749,hs8:139588787-139588787;hs9:1624743-1624743,hs9:1682033-1682033;hs9:3147234-3147234,hs9:5906789-5906789;hs9:22071852-22071852,hs9:26502846-26502846;hs11:39340722-39340722,hs11:48486777-48486777;hs11:106096264-106096264,hs11:124118376-124118376;hs14:42193229-42193229,hs14:43044808-43044808;hs15:52507787-52507787,hs15:53761708-53761708;hs16:51546616-51546616,hs16:64121812-64121812;hs1:74792478-74792478,hs1:76065256-76065256;hs2:57943555-57943555,hs2:122681951-122681951;hs2:164552575-164552575,hs2:168378700-168378700;hs2:178306107-178306107,hs2:190532495-190532495;hs3:86003798-86003798,hs15:52544930-52544930;hs3:87703641-87703641,hs15:54675076-54675076;hs3:115155729-115155729,hsX:3183174-3183174;hs4:27844711-27844711,hs4:95167071-95167071;hs4:135943420-135943420,hs4:137123865-137123865;hs4:27842120-27842120,hs6:76524106-76524106;hs5:90545223-90545223,hs5:120237484-120237484;hs6:125843913-125843913,hs6:126053498-126053498;hs8:32559232-32559232,hs8:43552072-43552072;hs8:50001571-50001571,hs8:52570515-52570515;hs8:73948540-73948540,hs8:79794511-79794511;hs8:79774499-79774499,hs8:80846934-80846934;hs8:128871825-128871825,hs8:128879145-128879145;hs8:32025920-32025920,hs8:43557518-43557518;hs9:3151660-3151660,hs9:3622838-3622838;hs9:4815577-4815577,hs9:25322806-25322806;hs9:6709112-6709112,hs9:24597564-24597564;hs11:49287620-49287620,hs11:50617978-50617978;hs11:92474484-92474484,hs11:93296046-93296046;hs13:61065813-61065813,hs13:90634375-90634375;hs14:39887340-39887340,hs14:42242719-42242719;hsX:2455194-2455194,hsX:4066756-4066756;hs2:49773472-49773472,hs2:51208489-51208489;hs3:84456694-84456694,hs3:90199717-90199717;hs3:85003733-85003733,hs15:54705099-54705099;hs4:95136910-95136910,hs4:136908830-136908830;hs4:135673338-135673338,hs4:136684728-136684728;hs5:19321201-19321201,hs5:21121226-21121226;hs8:49939587-49939587,hs8:50025000-50025000;hs8:51038773-51038773,hs8:52290090-52290090;hs8:80856946-80856946,hs8:128880521-128880521;hs8:128872898-128872898,hs8:128883878-128883878;hs8:130545199-130545199,hs8:137865060-137865060;hs9:23518088-23518088,hs9:26125080-26125080;hs13:60738822-60738822,hs13:92231190-92231190;hs13:64143269-64143269,hs13:85395863-85395863;hs1:15418738-15418738,hs1:16754968-16754968;hs2:80027309-80027309,hs2:80933382-80933382;hs2:125499785-125499785,hs7:48541441-48541441;hs3:86077291-86077291,hs15:53024265-53024265;hs3:86112420-86112420,hs15:54426448-54426448;hs4:28089372-28089372,hs4:28354821-28354821;hs4:133974315-133974315,hs4:136909899-136909899;hs4:136887824-136887824,hs4:136928611-136928611;hs4:134557930-134557930,hs4:136908865-136908865;hs4:137876905-137876905,hs6:76522771-76522771;hs5:20920680-20920680,hs5:21595298-21595298;hs5:90567606-90567606,hs5:120072268-120072268;hs6:81652151-81652151,hs8:137154041-137154041;hs8:32559354-32559354,hs8:43595433-43595433;hs8:49638191-49638191,hs8:137871849-137871849;hs9:5215504-5215504,hs9:25640788-25640788;hs11:47814735-47814735,hs11:50621976-50621976;hs14:39792179-39792179,hs14:40042512-40042512;hs11:48338375-48338375,hs11:49286883-49286883 ABCA13;AGPS;ARPP19;ASCC3;ASNSD1;BACH2;C8orf46;C8orf84;CADM2;CDKN2B-AS1;CHD1;CNGB3;CNTNAP2;CNTNAP5;COL22A1;CSMD1;CSMD3;CTAGE5;CTNNA2;DGKB;DIAPH3;DMD;EFCAB1;FAM155A;FAT3;FBXO33;FIGN;GABRA2;GALNT13;GPC5;GRID2;GTF3C3;IFT74;ITGB8;JAK2;KAZ;KDM4C;KHDRBS3;LINGO2;LMBR1;LRFN5;LRP1B;LRRTM4;LYRM4;MAGI2;MCTP1;MLANA;MLL3;MRPS28;MYO5A;MYO5C;MYO6;NECAB1;NRG1;NRXN1;NUP160;OPCML;OR8G1;P2RY10;PLAA;PPM1L;PVT1;PXDNL;RCL1;SEMA3E;SLC19A2;SLC44A5;SMARCA2;SMARCAD1;SNTG1;SPATA21;TDRD3;TERF1;TNNI3K;TRAPPC9;TRDN;UNC13C;VLDLR;WDR72; Harvard Medical School, Boston, MA 02115, USA The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term chromoplexy, frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. GRCh37/hg19 phs000447 Yes AGPS,ASNSD1;BACH2,TRDN;CADM2,MYO5C;CADM2,UNC13C;CNTNAP5,ABCA13;DIAPH3,GPC5;FBXO33,LRFN5;GRID2,SMARCAD1;KAZ,SPATA21;KHDRBS3,COL22A1;LRRTM4,GABRA2;MLL3,LMBR1;MRPS28,PVT1;NRXN1,LRRTM4;SMARCA2,KDM4C;SNTG1,PXDNL;TNNI3K,SLC44A5;VLDLR,IFT74 CTDB0274 Research 23622249 Baca SC, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, Van Allen E, Kryukov GV, Sboner A, Theurillat JP, Soong TD, Nickerson E, Auclair D, Tewari A, Beltran H, Onofrio RC, Boysen G, Guiducci C, Barbieri CE, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Ramos AH, Winckler W, Cipicchio M, Ardlie K, Kantoff PW, Berger MF, Gabriel SB, Golub TR, Meyerson M, Lander ES, Elemento O, Getz G, Demichelis F, Rubin MA, Garraway LA Punctuated evolution of prostate cancer genomes Cell 2013 Apr 1,2,4,5,6,7,8,10,12,13,15,X Prostate cancer Next Generation Sequencing Homo sapiens P05-620 Illumina GAIIx chr10:0-23237678:0;chr10:23237679-23243890:-1;chr10:23243891-67259926:0;chr10:67259927-67398527:-1;chr10:67398528-135534747:0;chr11:0-135006516:0;chr12:0-62573222:0;chr12:62573223-63019869:1;chr12:63019870-66589410:0;chr12:66589411-67022238:1;chr12:66923514-67276916:1;chr12:67276917-67290279:0;chr12:67290280-67833843:1;chr12:67833844-74402143:0;chr12:74402144-74403864:-1;chr12:74403865-133851895:0;chr13:0-21960784:0;chr13:21960785-21965786:-1;chr13:21965787-61971613:0;chr13:61971614-62019616:-1;chr13:62019617-76732889:0;chr13:76732890-76990686:-1;chr13:76990687-115169878:0;chr14:0-107349540:0;chr15:0-24846162:0;chr15:24846163-25443441:-1;chr15:25443442-26692126:0;chr15:26692127-27312456:1;chr15:26778044-27734326:1;chr15:27734327-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-61783994:0;chr18:61783995-61798279:-1;chr18:61798280-78077248:0;chr19:0-53456150:0;chr19:53456151-53464770:-1;chr19:53464771-59128983:0;chr1:0-89940882:0;chr1:100051217-100113749:-1;chr1:100051416-100316786:1;chr1:100316787-100339238:0;chr1:100339239-101225393:-1;chr1:100966492-101113771:-1;chr1:101225394-101342766:0;chr1:101342767-101670303:-1;chr1:101670304-104941031:0;chr1:104941032-104942463:-1;chr1:104942464-105199633:0;chr1:105199634-105231211:-1;chr1:105231212-165895495:0;chr1:165895496-165902275:-1;chr1:165902276-191429611:0;chr1:191429612-192122789:1;chr1:191742069-191748257:-1;chr1:192122790-193536090:0;chr1:193536091-193546727:-1;chr1:193546728-194907963:0;chr1:194907964-194961803:-1;chr1:194961804-197945128:0;chr1:197945129-197967453:-1;chr1:197967454-209654626:0;chr1:209654627-209664825:-1;chr1:209664826-216213939:0;chr1:216213940-216236536:-1;chr1:216236537-216514918:0;chr1:216514919-216537556:-1;chr1:216537557-249250621:0;chr1:89940883-89964328:-1;chr1:89964329-100051216:0;chr20:0-54302957:0;chr20:54302958-54304996:-1;chr20:54304997-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-79849404:0;chr2:116880900-116887260:-1;chr2:116887261-133305899:0;chr2:133305900-133829452:-1;chr2:133829453-145316080:0;chr2:145316081-145318089:-1;chr2:145318090-243199373:0;chr2:79849405-79853138:-1;chr2:79853139-89505438:0;chr2:89505439-89616536:-1;chr2:89616537-116880899:0;chr3:0-198022430:0;chr4:0-15805565:0;chr4:131842784-131850195:-1;chr4:131850196-132323031:0;chr4:132323032-132324109:-1;chr4:132324110-133297580:0;chr4:133297581-133301793:-1;chr4:133301794-157080964:0;chr4:157080965-157091282:-1;chr4:157091283-171845068:0;chr4:15805566-15879590:1;chr4:15861729-15899040:1;chr4:15899041-18891350:0;chr4:171845069-171863784:-1;chr4:171863785-173611229:0;chr4:173611230-173628959:-1;chr4:173628960-178300469:0;chr4:178300470-178309103:-1;chr4:178309104-178923082:0;chr4:178923083-178941844:-1;chr4:178941845-179758380:0;chr4:179758381-179759970:-1;chr4:179759971-180317355:0;chr4:180317356-181021573:-1;chr4:181021574-183729904:0;chr4:183729905-184596688:1;chr4:184596689-191154276:0;chr4:18891351-18914771:-1;chr4:18914772-27553968:0;chr4:27553969-27620082:-1;chr4:27620083-59335618:0;chr4:59335619-59338986:-1;chr4:59338987-59530133:0;chr4:59530134-59537186:-1;chr4:59537187-59601286:0;chr4:59601287-60543627:1;chr4:60475726-60512189:-1;chr4:60543628-60834827:0;chr4:60834828-60837233:-1;chr4:60837234-131842783:0;chr5:0-24779268:0;chr5:104112525-104204836:-1;chr5:104204837-180915260:0;chr5:24779269-24827513:-1;chr5:24827514-82918266:0;chr5:82918267-83432353:-1;chr5:83432354-104112524:0;chr6:0-62967531:0;chr6:111210189-111213490:-1;chr6:111213491-121281823:0;chr6:121281824-121292267:-1;chr6:121292268-121683783:0;chr6:121683784-121695523:-1;chr6:121695524-123425084:0;chr6:123425085-123469226:-1;chr6:123469227-126003805:0;chr6:126003806-126074563:-1;chr6:126074564-126557767:0;chr6:126557768-126569042:-1;chr6:126569043-131431646:0;chr6:131431647-131707387:-1;chr6:131707388-132160114:0;chr6:132160115-132169193:-1;chr6:132169194-160784629:0;chr6:160784630-160872378:-1;chr6:160872379-162590274:0;chr6:162590275-163582215:-1;chr6:163582216-171115067:0;chr6:62967532-62990158:-1;chr6:62990159-66908030:0;chr6:66908031-66923717:-1;chr6:66923718-87465548:0;chr6:87465549-87918606:-1;chr6:87918607-98052180:0;chr6:98052181-98060243:-1;chr6:98060244-111210188:0;chr7:0-31519874:0;chr7:118842562-118857332:-1;chr7:118857333-159138663:0;chr7:31519875-31528771:-1;chr7:31528772-39210036:0;chr7:39210037-39216229:-1;chr7:39216230-118842561:0;chr8:0-62109543:0;chr8:112988275-113028405:-1;chr8:113028406-146364022:0;chr8:62109544-62328199:-1;chr8:62328200-84101482:0;chr8:84101483-84105168:-1;chr8:84105169-88615760:0;chr8:88615761-88620689:-1;chr8:88620690-89044907:0;chr8:89044908-89049320:-1;chr8:89049321-112988274:0;chr9:0-141213431:0;chrX:0-88032953:0;chrX:141238224-141240915:-1;chrX:141240916-147818449:0;chrX:147818450-148509392:-1;chrX:148509393-155270560:0;chrX:88032954-88043151:-1;chrX:88043152-141238223:0;chrY:0-59373566:0 hs8:56810455-56810455,hs8:65592915-65592915;hs2:125462458-125462458,hs2:145209253-145209253;hs8:73276503-73276503,hs8:73890298-73890298;hs1:196578285-196578285,hs4:178036678-178036678;hs1:198955457-198955457,hs8:4678667-4678667;hs1:192421318-192421318,hs1:195350566-195350566;hs1:194181026-194181026,hs7:13215210-13215210;hs4:176195677-176195677,hs4:178457547-178457547;hs8:62148304-62148304,hs8:63545550-63545550;hs2:127129882-127129882,hs2:128412702-128412702;hs8:62246507-62246507,hs8:63569350-63569350;hs6:161705083-161705083,hs6:162639051-162639051;hs1:194846739-194846739,hs4:178193722-178193722;hs6:91906910-91906910,hs6:158713298-158713298;hs1:99927244-99927244,hs1:167477765-167477765;hs6:125589064-125589064,hs6:127430878-127430878;hs8:85936947-85936947,hs15:45966896-45966896;hs4:15823634-15823634,hs4:15837447-15837447;hs4:15942539-15942539,hs4:18634695-18634695;hs4:29277825-29277825,hs4:29931108-29931108;hs8:107229043-107229043,hs15:24855905-24855905;hs1:192404446-192404446,hs1:195414869-195414869;hs4:180927341-180927341,hs8:73516235-73516235;hs6:94858632-94858632,hs6:163320927-163320927;hs6:158656595-158656595,hs6:160875000-160875000;hs5:96316324-96316324,hs5:101798117-101798117;hs8:107250196-107250196,hs15:24300176-24300176;hs10:107979361-107979361,hs13:84621856-84621856;hs2:124942808-124942808,hs2:127043825-127043825;hs4:15834442-15834442,hs4:16592388-16592388;hs4:133475459-133475459,hs4:179810860-179810860;hs4:21270283-21270283,hs4:67042609-67042609;hs8:56273786-56273786,hs8:64778816-64778816;hs12:66578773-66578773,hs12:67163425-67163425;hs4:92026444-92026444,hs4:185829686-185829686;hs6:162918002-162918002,hs6:164683680-164683680;hs8:131732072-131732072,hs8:139730471-139730471;hs4:16540932-16540932,hs4:18587272-18587272;hs6:125186492-125186492,hs6:135135110-135135110;hs6:125410905-125410905,hs6:132712803-132712803;hs6:131700035-131700035,hs6:157971524-157971524;hs8:108025540-108025540,hs15:24051005-24051005;hs13:76725877-76725877,hs13:76755026-76755026;hs4:18647922-18647922,hs8:3145615-3145615;hs5:100545089-100545089,hs5:104194500-104194500;hs11:89058578-89058578,hs11:99110479-99110479;hs1:186135701-186135701,hs4:178411002-178411002;hs4:6130136-6130136,hs4:21318269-21318269;hs6:96097405-96097405,hs6:158524772-158524772;hs6:126781866-126781866,hs6:164871401-164871401;hs12:63013508-63013508,hs12:63020462-63020462;hs12:67026003-67026003,hs12:67447744-67447744;hs2:90145301-90145301,hs4:184354014-184354014;hs6:158407066-158407066,hs6:160926358-160926358;hs6:84404272-84404272,hs6:87033807-87033807;hs10:94956027-94956027,hs10:110075482-110075482;hs15:24037511-24037511,hs15:25442480-25442480;hs1:192653513-192653513,hs1:193767647-193767647;hs1:100813769-100813769,hs1:167189990-167189990;hs4:183473868-183473868,hs4:184885361-184885361;hs6:125630984-125630984,hs6:162569426-162569426;hs6:126768392-126768392,hs6:162398716-162398716;hs6:162685336-162685336,hs6:163340562-163340562;hs1:100925917-100925917,hs1:166767217-166767217;hs1:186119005-186119005,hs4:180123557-180123557;hs2:48949755-48949755,hs2:89102446-89102446;hs5:2761791-2761791,hs5:2996449-2996449;hs5:82882354-82882354,hs5:83432343-83432343;hs5:96316273-96316273,hs5:96337237-96337237;hs5:6545999-6545999,hs6:101114054-101114054;hs5:6548893-6548893,hs6:99794916-99794916;hs5:21581293-21581293,hs15:21909266-21909266;hs6:124986724-124986724,hs6:134308216-134308216;hs6:93195207-93195207,hs6:158685884-158685884;hs6:162545011-162545011,hs6:164954138-164954138;hs8:57409680-57409680,hs8:65562792-65562792;hs1:100394811-100394811,hs1:101589381-101589381;hs4:184508853-184508853,hs4:185970528-185970528;hs5:101629139-101629139,hs5:131092106-131092106;hs6:96224120-96224120,hs6:131919096-131919096;hs6:132280212-132280212,hs6:135187355-135187355;hs6:90181445-90181445,hs6:130598672-130598672;hs6:131654820-131654820,hs6:163245621-163245621;hs6:164228240-164228240,hs6:164346061-164346061;hs6:162372999-162372999,hs6:163580154-163580154;hs8:127517917-127517917,hs8:129782461-129782461;hs12:62693092-62693092,hs12:66943321-66943321;hs1:190843612-190843612,hs1:195124418-195124418;hs1:192629583-192629583,hs1:196568034-196568034;hs6:123640373-123640373,hs6:134056530-134056530;hs8:127518587-127518587,hs8:134985629-134985629;hs15:24268997-24268997,hs15:25955408-25955408;hs4:133446180-133446180,hs8:4694827-4694827;hs5:82882618-82882618,hs5:82922131-82922131;hs5:102151376-102151376,hs5:104115548-104115548;hs6:84250256-84250256,hs6:87001331-87001331;hs8:73155137-73155137,hs8:73826685-73826685;hs8:64791915-64791915,hs8:65178161-65178161;hs10:108381015-108381015,hs13:37185166-37185166;hs12:62978218-62978218,hs12:68506526-68506526;hs1:101071721-101071721,hs1:167367142-167367142;hs1:101840050-101840050,hs1:167459411-167459411;hs1:198982213-198982213,hs4:178929931-178929931;hs2:90413051-90413051,hs4:92055341-92055341;hs6:95435348-95435348,hs6:129812314-129812314;hs6:129813770-129813770,hs6:131451904-131451904;hs12:65714884-65714884,hs12:67193789-67193789;hs13:76713009-76713009,hs13:76990475-76990475;hs5:91488451-91488451,hs5:101662100-101662100;hs8:60832556-60832556,hs8:76254459-76254459;hs8:113031381-113031381,hs8:125519487-125519487;hs8:129781279-129781279,hs8:136302122-136302122;hs11:90163145-90163145,hs11:99139823-99139823;hs12:62556459-62556459,hs12:67856891-67856891;hsX:143055545-143055545,hsX:143879422-143879422;hs1:49214573-49214573,hs22:29065571-29065571;hs4:6152411-6152411,hs4:67010476-67010476;hs4:43987907-43987907,hs4:60390382-60390382;hs4:64638098-64638098,hs8:3110857-3110857;hs5:2772015-2772015,hs5:3017067-3017067;hs5:21615052-21615052,hs5:24389950-24389950;hs6:90118651-90118651,hs6:95432715-95432715;hs6:91903885-91903885,hs6:158688886-158688886;hs6:164157096-164157096,hs6:164668988-164668988;hs8:107994919-107994919,hs15:26766394-26766394;hs1:99675588-99675588,hs1:167113034-167113034;hs1:190837823-190837823,hs1:191830533-191830533;hs1:100786256-100786256,hs1:166951842-166951842;hs4:19058423-19058423,hs4:21229509-21229509;hs6:164292388-164292388,hs6:164841746-164841746;hs1:100018129-100018129,hs1:100264018-100264018;hs1:193394614-193394614,hs4:175732008-175732008;hs6:84284880-84284880,hs6:86971087-86971087;hs6:124224874-124224874,hs6:134323343-134323343;hs8:88279448-88279448,hs15:27350549-27350549;hs12:66537055-66537055,hs12:66923473-66923473;hs6:91549481-91549481,hs6:94975493-94975493;hs6:132352913-132352913,hs6:135532539-135532539;hs6:162603941-162603941,hs6:163046223-163046223;hs1:100341220-100341220,hs1:101702665-101702665;hs6:94748657-94748657,hs6:157968651-157968651;hs6:95326369-95326369,hs6:158357787-158357787;hs6:127542090-127542090,hs6:132033242-132033242;hs6:131613078-131613078,hs6:158686525-158686525;hs8:84071457-84071457,hs8:85937059-85937059;hs1:100992488-100992488,hs1:101510327-101510327;hs2:128258299-128258299,hs2:142409287-142409287;hs4:60474617-60474617,hs4:60574360-60574360;hs4:156137957-156137957,hs4:171990531-171990531;hs4:180375785-180375785,hs8:73526303-73526303;hs8:134987171-134987171,hs8:140316196-140316196;hs1:100729399-100729399,hs1:167425113-167425113;hs2:125345545-125345545,hs2:142448341-142448341;hs6:162288530-162288530,hs6:165331505-165331505;hs8:84059520-84059520,hs15:22379877-22379877;hs12:66924366-66924366,hs12:67408729-67408729;hs1:193383121-193383121,hs1:193740871-193740871;hs4:27901808-27901808,hs4:29898936-29898936;hs5:120607071-120607071,hs5:121607396-121607396;hs6:125156875-125156875,hs6:135506589-135506589;hs10:42681702-42681702,hs10:66810215-66810215;hs1:100808588-100808588,hs1:167025707-167025707;hs1:194107616-194107616,hs5:109460644-109460644;hs2:90139884-90139884,hs2:91670921-91670921;hs5:113319208-113319208,hs13:104369327-104369327;hs6:95533173-95533173,hs6:160218013-160218013;hs6:158531168-158531168,hs6:163247388-163247388;hs10:42684183-42684183,hs10:66255264-66255264;hs4:178194565-178194565,hs4:180145710-180145710;hs4:44105900-44105900,hs4:59413032-59413032;hs4:183728241-183728241,hs22:16856412-16856412;hs6:95389941-95389941,hs6:127711905-127711905;hs10:23513155-23513155,hs10:34059751-34059751;hs4:178924759-178924759,hs8:29530684-29530684;hs5:113007416-113007416,hs13:103205650-103205650;hs6:124803946-124803946,hs6:134137066-134137066;hs6:127829838-127829838,hs6:159829948-159829948;hs8:59673850-59673850,hs8:76816285-76816285;hs8:75633416-75633416,hs8:79581272-79581272;hs10:5163799-5163799,hs10:15140864-15140864;hs10:8868296-8868296,hs10:30129298-30129298;hs10:10928840-10928840,hs10:32649003-32649003;hs10:12259032-12259032,hs10:33866485-33866485;hs4:179399386-179399386,hs4:180432402-180432402;hs5:112653636-112653636,hs13:80438197-80438197;hs5:120574112-120574112,hs13:90216945-90216945;hs8:56843444-56843444,hs8:57467409-57467409;hs10:4644798-4644798,hs10:37007206-37007206;hs10:5471537-5471537,hs10:29305420-29305420;hs10:5475046-5475046,hs10:25423968-25423968;hs10:5742958-5742958,hs10:15185588-15185588;hs10:17058145-17058145,hs10:21996615-21996615;hs10:31810183-31810183,hs10:32928750-32928750 AFF2;AGL;AMD1;ANKRD6;ARMC3;ASCC3;ATP10A;BEND5;C10orf18;C10orf68;C18orf20;C4orf41;C6orf168;C6orf174;CD247;CD38;CDC123;CDC14A;CLVS1;CNBD1;CNTN5;CNTNAP5;COL22A1;CSMD1;CTNNA2;CUBN;CYP7B1;EDIL3;ENPP1;ENPP3;EXTL2;FAM164A;FAM190A;FAM19A2;FGFBP1;FLJ40330;FNIP1;GABRG3;GALNTL6;GLRA3;GPA33;GPR39;GRIP1;GUSBP1;HEY2;HMCN1;IRAK3;IWS1;JAKMIP1;KCNB2;KCNT2;KHDRBS2;LAMA2;LDB2;LHCGR;LIMS2;LNPEP;LOC286094;LPAL2;LRP1B;LYN;MCC;MED23;MLLT10;MON2;MOXD1;MRPL18;MSRB3;MYB;NCKAP5;NET1;NKAIN2;NKAIN3;NMT2;NOX4;NPY2R;ODZ3;OR4N4;PACRG;PALMD;PARK2;POU2F1;POU6F2;RPP38;RRAGD;RTCD1;S1PR1;SERAC1;SLC22A3;SLC2A12;SLCO4C1;SLCO6A1;SNAP91;SNORD115;SNX9;SORCS1;SQRDL;STOX2;SYNJ2;TATDN1;TBPL1;TMBIM4;TRDN;TTC28;USH2A;USP15;XKR4;ZDHHC14;ZDHHC20;ZEB1;ZEB2;ZNF292;ZNF816A; Harvard Medical School, Boston, MA 02115, USA The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term chromoplexy, frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. GRCh37/hg19 phs000447 Yes AGL,S1PR1;BEND5,TTC28;C10orf18,NMT2;CD38,LDB2;CLVS1,NKAIN3;CNBD1,GABRG3;CNTNAP5,LRP1B;CNTNAP5,ZEB2;CUBN,MLLT10;GPR39,NCKAP5;IRAK3,GRIP1;IWS1,LRP1B;JAKMIP1,KCNIP4;LHCGR,FLJ40330;LNPEP,SLCO6A1;LYN,CYP7B1;NKAIN2,SLC2A12;NKAIN2,TBPL1;ODZ3,STOX2;PARK2,PACRG;RTCD1,CD247;SERAC1,PACRG;SLCO4C1,FNIP1;SYNJ2,LPAL2;TMBIM4,GRIP1;USP15,GRIP1;ZEB1,C10orf68 CTDB0275 Research 23622249 Baca SC, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, Van Allen E, Kryukov GV, Sboner A, Theurillat JP, Soong TD, Nickerson E, Auclair D, Tewari A, Beltran H, Onofrio RC, Boysen G, Guiducci C, Barbieri CE, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Ramos AH, Winckler W, Cipicchio M, Ardlie K, Kantoff PW, Berger MF, Gabriel SB, Golub TR, Meyerson M, Lander ES, Elemento O, Getz G, Demichelis F, Rubin MA, Garraway LA Punctuated evolution of prostate cancer genomes Cell 2013 Apr 1,2,3,4,5,6,7,8,9,10,11.12,13,14,16,18 Prostate cancer Next Generation Sequencing Homo sapiens P07-837 Illumina GAIIx chr10:0-48306147:0;chr10:48306148-48308685:-1;chr10:48308686-56887177:0;chr10:56887178-57278579:-1;chr10:57278580-58351326:0;chr10:58351327-58353667:-1;chr10:58353668-91455960:0;chr10:91455961-91457753:-1;chr10:91457754-135534747:0;chr11:0-100455595:0;chr11:100455596-100458880:-1;chr11:100458881-101032307:0;chr11:101032308-101046549:-1;chr11:101046550-101227741:0;chr11:101227742-101229298:-1;chr11:101229299-122554109:0;chr11:122554110-122592020:-1;chr11:122592021-135006516:0;chr12:0-18093018:0;chr12:130470361-130475618:-1;chr12:130475619-133851895:0;chr12:18093019-18132905:-1;chr12:18132906-82083659:0;chr12:82083660-82086191:-1;chr12:82086192-83914810:0;chr12:83914811-83940823:-1;chr12:83940824-83946194:0;chr12:83946195-83951946:-1;chr12:83951947-130470360:0;chr13:0-49466741:0;chr13:49466742-49470127:-1;chr13:49470128-66306134:0;chr13:66306135-66345555:-1;chr13:66345556-67361323:0;chr13:67361324-67378876:-1;chr13:67378877-71313228:0;chr13:71313229-71314931:-1;chr13:71314932-85275132:0;chr13:85275133-85406868:-1;chr13:85406869-115169878:0;chr14:0-29254698:0;chr14:29254699-29256010:-1;chr14:29256011-107349540:0;chr15:0-102531392:0;chr16:0-46786125:0;chr16:46786126-46792736:-1;chr16:46792737-60099927:0;chr16:60099928-60107713:-1;chr16:60107714-65191699:0;chr16:65191700-65193852:-1;chr16:65193853-90354753:0;chr17:0-81195210:0;chr18:0-58870645:0;chr18:58870646-58888958:-1;chr18:58888959-78077248:0;chr19:0-59128983:0;chr1:0-74275561:0;chr1:157437672-157483853:-1;chr1:157483854-157529865:0;chr1:157529866-157991572:-1;chr1:157991573-191100804:0;chr1:191100805-191764780:-1;chr1:191764781-195158205:0;chr1:195158206-195162275:-1;chr1:195162276-195687563:0;chr1:195687564-196331431:1;chr1:196331432-213936324:0;chr1:213936325-213978828:-1;chr1:213978829-213985252:0;chr1:213985253-214291488:-1;chr1:214291489-249250621:0;chr1:74275562-74543357:-1;chr1:74543358-74717562:0;chr1:74717563-74734684:-1;chr1:74734685-98868286:0;chr1:98868287-98879108:-1;chr1:98879109-157437671:0;chr20:0-63025520:0;chr21:0-33244273:0;chr21:33244274-33257808:1;chr21:33257809-48129895:0;chr22:0-51304566:0;chr2:0-36783130:0;chr2:108600786-108603058:-1;chr2:108603059-115587112:0;chr2:115587113-116104622:-1;chr2:116104623-126683099:0;chr2:126683100-126690201:-1;chr2:126690202-200198016:0;chr2:200198017-200202450:-1;chr2:200202451-243199373:0;chr2:36783131-36792425:-1;chr2:36792426-41506590:0;chr2:41506591-41510095:-1;chr2:41510096-108600785:0;chr3:0-13560059:0;chr3:13560060-13975783:-1;chr3:13975784-97478252:0;chr3:160498400-160509709:-1;chr3:160509710-198022430:0;chr3:97478253-97490714:1;chr3:97490715-160498399:0;chr4:0-63461618:0;chr4:101851372-101860883:-1;chr4:101860884-118459739:0;chr4:118459740-118496684:-1;chr4:118496685-131078247:0;chr4:131078248-131341209:-1;chr4:131341210-136847779:0;chr4:136847780-137719893:-1;chr4:137719894-158636194:0;chr4:158636195-158659698:-1;chr4:158659699-165480854:0;chr4:165480855-165482531:-1;chr4:165482532-180509325:0;chr4:180509326-181369943:-1;chr4:181369944-191154276:0;chr4:63461619-63749508:-1;chr4:63749509-101851371:0;chr5:0-25746136:0;chr5:101426460-101616895:1;chr5:101616896-102031693:0;chr5:102031694-102685835:-1;chr5:102174970-102344661:-1;chr5:102685836-180915260:0;chr5:25746137-25849725:-1;chr5:25849726-28668691:0;chr5:28668692-28671091:-1;chr5:28671092-91996106:0;chr5:91996107-92031510:-1;chr5:92031511-92465034:0;chr5:92465035-92471311:-1;chr5:92471312-97046165:0;chr5:97046166-97359160:1;chr5:97359161-97819013:0;chr5:97819014-97910310:-1;chr5:97910311-98601120:0;chr5:98601121-98848867:1;chr5:98667029-99104792:1;chr5:99104793-99659596:0;chr5:99659597-99738763:-1;chr5:99738764-101426459:0;chr6:0-48899576:0;chr6:48899577-48902556:-1;chr6:48902557-56208185:0;chr6:56208186-56209956:-1;chr6:56209957-84846953:0;chr6:84846954-84907408:-1;chr6:84907409-97023511:0;chr6:97023512-97071598:-1;chr6:97071599-171115067:0;chr7:0-32521336:0;chr7:149299057-150055949:1;chr7:150055950-159138663:0;chr7:32521337-32639855:-1;chr7:32639856-52944488:0;chr7:52944489-52945925:-1;chr7:52945926-61065859:0;chr7:61065860-61850256:-1;chr7:61850257-83867078:0;chr7:83867079-83890714:-1;chr7:83890715-84554812:0;chr7:84554813-84941346:-1;chr7:84941347-149299056:0;chr8:0-35009330:0;chr8:35009331-35037790:-1;chr8:35037791-47609563:0;chr8:47609564-48138941:-1;chr8:48138942-64626657:0;chr8:64626658-64644053:-1;chr8:64644054-146364022:0;chr9:0-8117074:0;chr9:8117075-8813716:1;chr9:8746203-8847456:-1;chr9:8847457-141213431:0;chrX:0-44726064:0;chrX:44726065-44736052:-1;chrX:44736053-155270560:0;chrY:0-59373566:0 hs8:33588296-33588296,hs8:33843616-33843616;hs7:84933870-84933870,hs7:114253520-114253520;hs7:84033328-84033328,hs7:113043568-113043568;hs8:33614817-33614817,hs8:33874889-33874889;hs2:200250719-200250719,hs2:201160988-201160988;hs8:14746503-14746503,hs8:111260220-111260220;hs10:53905507-53905507,hs10:87951131-87951131;hs10:58095842-58095842,hs10:88478649-88478649;hs10:57678808-57678808,hs10:59705957-59705957;hs10:54007781-54007781,hs10:56920590-56920590;hs10:54732741-54732741,hs10:89437360-89437360;hs2:140822337-140822337,hs2:144884592-144884592;hs7:31817133-31817133,hs7:32630687-32630687;hs2:200754412-200754412,hs2:201127456-201127456;hs2:199062410-199062410,hs2:200131764-200131764;hs2:147734440-147734440,hs2:200270867-200270867;hs10:88533676-88533676,hs10:89328366-89328366;hs4:115105928-115105928,hs4:137702103-137702103;hs2:95673692-95673692,hs2:143014762-143014762;hs10:26515515-26515515,hs10:27822918-27822918;hs10:26531684-26531684,hs10:38816762-38816762;hs10:54645063-54645063,hs10:89968876-89968876;hs10:56420947-56420947,hs10:89497236-89497236;hs10:66274629-66274629,hs10:68838301-68838301;hs1:762002-762002,hs1:74299527-74299527;hs2:115572704-115572704,hs2:117913952-117913952;hs4:26551152-26551152,hs4:33312895-33312895;hs5:102127592-102127592,hs5:108762273-108762273;hs8:34272676-34272676,hs8:34882967-34882967;hs2:147730228-147730228,hs2:200614134-200614134;hs8:34867250-34867250,hs8:34938169-34938169;hs9:73891949-73891949,hs16:60098061-60098061;hs13:43230827-43230827,hs13:104314314-104314314;hs18:61406022-61406022,hs18:64291934-64291934;hs2:142128457-142128457,hs2:147045065-147045065;hs5:97872248-97872248,hs5:101803846-101803846;hs5:90962151-90962151,hs5:109653059-109653059;hs5:99757302-99757302,hs5:103018159-103018159;hs6:76095596-76095596,hs6:77452429-77452429;hs12:13145495-13145495,hs12:14816487-14816487;hs4:35148398-35148398,hs4:38684253-38684253;hs4:136337349-136337349,hs4:137354929-137354929;hs4:102375591-102375591,hs4:172304283-172304283;hs2:95684212-95684212,hs2:143985205-143985205;hs2:140890914-140890914,hs2:142321812-142321812;hs2:143385731-143385731,hs2:145769369-145769369;hs5:27281497-27281497,hs5:30657590-30657590;hs10:26914737-26914737,hs10:38975815-38975815;hs10:57265019-57265019,hs10:59682128-59682128;hs13:103759978-103759978,hs13:103785861-103785861;hs2:200110714-200110714,hs2:201127452-201127452;hs4:26553134-26553134,hs4:34670117-34670117;hs5:94307471-94307471,hs5:112932279-112932279;hs6:72671416-72671416,hs6:77439116-77439116;hs6:85315283-85315283,hs6:127167886-127167886;hs11:22578584-22578584,hs11:30943858-30943858;hs13:103721577-103721577,hs13:103951641-103951641;hs7:56789380-56789380,hs7:61849443-61849443;hs9:69949712-69949712,hs12:72332556-72332556;hs10:59049094-59049094,hs10:89674692-89674692;hs12:11525478-11525478,hs12:14577800-14577800;hs14:43788270-43788270,hs14:44719914-44719914;hs1:706267-706267,hs1:72916861-72916861;hs1:737899-737899,hs1:74540268-74540268;hs2:144876901-144876901,hs2:145316854-145316854;hs3:164237612-164237612,hs3:166133040-166133040;hs5:24804636-24804636,hs5:26106392-26106392;hs5:100607963-100607963,hs5:102846735-102846735;hs5:98899849-98899849,hs5:109608510-109608510;hs10:47058982-47058982,hs10:48564484-48564484;hs13:104311724-104311724,hs18:28146617-28146617;hs14:43781666-43781666,hs14:43988740-43988740;hs4:63749440-63749440,hs4:66297218-66297218;hs4:102366802-102366802,hs4:173437530-173437530;hs5:98479236-98479236,hs5:101326185-101326185;hs9:73896254-73896254,hs16:60354240-60354240;hs12:130699424-130699424,hsX:78054430-78054430;hs1:190508608-190508608,hs1:191783075-191783075;hs4:168144907-168144907,hs4:172399634-172399634;hs4:67636395-67636395,hs18:76098686-76098686;hs5:26799993-26799993,hs5:27509318-27509318;hs5:27512756-27512756,hs5:31299574-31299574;hs5:28987821-28987821,hs5:31819765-31819765;hs5:99165731-99165731,hs5:101803370-101803370;hs12:59565994-59565994,hs12:62888583-62888583;hs1:71592235-71592235,hs1:72733359-72733359;hs2:115557447-115557447,hs2:117905792-117905792;hs4:112458537-112458537,hs4:131833342-131833342;hs5:100865426-100865426,hs5:102928558-102928558;hs9:33093138-33093138,hs13:78701969-78701969;hs10:58913796-58913796,hs10:89269899-89269899;hs12:13776418-13776418,hs12:14884906-14884906;hs12:130699894-130699894,hsX:78051797-78051797;hs18:70004106-70004106,hs18:70023150-70023150;hs2:116076325-116076325,hs21:10913733-10913733;hs3:164237353-164237353,hs3:166133041-166133041;hs4:137818310-137818310,hs4:138893454-138893454;hs9:7697056-7697056,hs9:8085528-8085528;hs9:11070372-11070372,hs9:12605537-12605537;hs13:67123892-67123892,hs13:80950514-80950514;hs18:26790355-26790355,hs18:26872269-26872269;hs5:102078341-102078341,hs5:103758542-103758542;hs10:58136300-58136300,hs10:89905580-89905580;hs12:12631552-12631552,hs12:13279501-13279501;hs1:107388367-107388367,hs1:109527179-109527179;hs1:107986916-107986916,hs1:109517199-109517199;hs2:147735627-147735627,hs2:200577247-200577247;hs4:114169205-114169205,hs4:181362016-181362016;hs4:131092631-131092631,hs4:132939712-132939712;hs5:28771296-28771296,hs5:30663982-30663982;hs5:98576047-98576047,hs5:102190725-102190725;hs5:100630262-100630262,hs5:110366368-110366368;hs5:102147540-102147540,hs5:103028688-103028688;hs5:100024230-100024230,hs5:103470093-103470093;hs9:44236765-44236765,hs12:73798790-73798790;hs13:62595062-62595062,hs13:63844662-63844662;hs18:26837238-26837238,hs18:26896222-26896222;hs1:190443642-190443642,hs1:196372708-196372708;hs4:33825042-33825042,hs4:34667709-34667709;hs5:99159651-99159651,hs5:100349735-100349735;hs5:99298092-99298092,hs5:101855689-101855689;hs5:108683646-108683646,hs5:110679610-110679610;hs6:73023008-73023008,hs6:77452272-77452272;hs13:43234255-43234255,hs18:28163706-28163706;hs13:103138228-103138228,hs18:14519524-14519524;hs1:191241562-191241562,hs1:192340773-192340773;hs4:131318885-131318885,hs4:132912410-132912410;hs4:33575344-33575344,hs4:35140144-35140144;hs5:98635838-98635838,hs5:100337142-100337142;hs5:99327196-99327196,hs5:100798921-100798921;hs5:97368661-97368661,hs5:110674156-110674156;hs9:7700615-7700615,hs9:8750594-8750594;hs10:26916557-26916557,hs10:38818072-38818072;hs10:60035928-60035928,hs10:89573285-89573285;hs13:81232802-81232802,hs13:81271586-81271586;hs1:70676252-70676252,hs1:103272471-103272471;hs1:190323493-190323493,hs1:192078112-192078112;hs1:191122275-191122275,hs2:87567742-87567742;hs1:191122275-191122275,hs2:91759072-91759072;hs4:112452846-112452846,hs4:114178878-114178878;hs5:98288508-98288508,hs5:103819279-103819279;hs5:99751825-99751825,hs5:103512006-103512006;hs5:110675512-110675512,hs5:110679634-110679634;hs6:86566591-86566591,hs6:93727676-93727676;hs6:66226086-66226086,hs6:72648290-72648290;hs10:57875830-57875830,hs10:59504801-59504801;hs12:12378689-12378689,hs12:13883181-13883181;hs16:60087115-60087115,hs16:87273335-87273335;hs5:98065899-98065899,hs5:101662586-101662586;hs5:102343728-102343728,hs5:110714411-110714411;hs10:57548570-57548570,hs10:89275794-89275794;hs12:39834381-39834381,hs12:40422135-40422135;hs4:137308932-137308932,hs4:137369948-137369948;hs5:98286770-98286770,hs5:100723312-100723312;hs5:98417833-98417833,hs5:101356333-101356333;hs5:100814658-100814658,hs5:102429812-102429812;hs9:33100015-33100015,hs13:78705107-78705107;hs11:22551767-22551767,hs11:29929652-29929652;hs4:33835256-33835256,hs4:37911919-37911919;hs5:99778584-99778584,hs5:100507483-100507483;hs1:70635851-70635851,hs1:103128526-103128526;hs1:72911807-72911807,hs1:75765120-75765120;hs1:106339586-106339586,hs1:107396558-107396558;hs4:63465092-63465092,hs4:66288627-66288627;hs4:168151298-168151298,hs4:173437755-173437755;hs5:98288595-98288595,hs5:101537755-101537755;hs5:99132826-99132826,hs5:102556480-102556480;hs5:101806282-101806282,hs5:102346046-102346046;hs5:85674461-85674461,hs9:45720661-45720661;hs6:29920502-29920502,hs15:47306810-47306810;hs7:56799948-56799948,hs7:61850236-61850236;hs10:54643340-54643340,hs10:89245529-89245529;hs10:57935297-57935297,hs10:60014719-60014719;hs4:33854465-33854465,hs4:37911698-37911698;hs4:134340196-134340196,hs4:180516699-180516699;hs5:100554074-100554074,hs5:101551666-101551666;hs11:29903497-29903497,hs11:30953569-30953569;hs12:39833531-39833531,hs12:40400963-40400963;hs4:115092905-115092905,hs4:137407237-137407237;hs5:97350494-97350494,hs5:99602951-99602951;hs13:63705938-63705938,hs13:63872531-63872531 ANK2;ARHGAP15;ARL6;ATAD1;ATF7IP;BMPR1A;C14orf23;CAMK4;CDH6;CISD1;DPP10;DUSP16;EPHA5;EYS;FAM5C;FCRL5;FEZ2;FHL5;FILIP1;FOXP2;GAD2;GALNTL6;GIN1;GRID1;GRIN2B;GTDC1;GUCY2C;HEBP1;HUNK;IPMK;KCNT2;KDM6A;KIAA1009;KIF21A;KIRREL;KLF3;LDB3;LRP1B;LRP6;LRRC40;LRRIQ3;LRRTM3;MCTP1;MINPP1;MON2;NCRNA00115;NEGR1;NTNG1;PAM;PAPSS2;PCDH15;PCDH9;PDZD2;PJA2;POTEC;PPFIA2;PPM1L;PRKG1;PTEN;PTPRD;RAB18;RIMS1;SATB2;SFRS11;SGCZ;SLC10A2;SLC2A13;SLC44A5;SLC5A7;SLCO4C1;SLCO6A1;SPOCK3;TBC1D1;TNNI3K;TPH2;TPTE;UBASH3B;WDR47;ZNF767; Harvard Medical School, Boston, MA 02115, USA The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term chromoplexy, frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. GRCh37/hg19 phs000447 Yes CISD1,ATAD1;DPP10,TPTE;EYS,RIMS1;FAM5C,KCNT2;GAD2,RAB18;HEBP1,GUCY2C;KIF21A,SLC2A13;LRP6,GRIN2B;NTNG1,WDR47;PAM,CAMK4;PCDH15,PAPSS2;PJA2,CAMK4;PRKG1,GRID1;SLCO6A1,PAM;SPOCK3,GALNTL6 CTDB0276 Research 23622249 Baca SC, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, Van Allen E, Kryukov GV, Sboner A, Theurillat JP, Soong TD, Nickerson E, Auclair D, Tewari A, Beltran H, Onofrio RC, Boysen G, Guiducci C, Barbieri CE, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Ramos AH, Winckler W, Cipicchio M, Ardlie K, Kantoff PW, Berger MF, Gabriel SB, Golub TR, Meyerson M, Lander ES, Elemento O, Getz G, Demichelis F, Rubin MA, Garraway LA Punctuated evolution of prostate cancer genomes Cell 2013 Apr 1,2,3,4,5,6,8,9,11,13,15,17,18,21,22 Prostate cancer Next Generation Sequencing Homo sapiens PR-06-1749 Illumina GAIIx chr10:0-135534747:0;chr11:0-7914766:0;chr11:101447905-101750599:-1;chr11:101750600-102052668:0;chr11:102052669-102129853:-1;chr11:102129854-127388713:0;chr11:127388714-127406374:-1;chr11:127406375-135006516:0;chr11:39570237-39586783:-1;chr11:39586784-101447904:0;chr11:7914767-7923623:-1;chr11:7923624-39570236:0;chr12:0-133851895:0;chr13:0-53482287:0;chr13:53482288-53642288:-1;chr13:53642289-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-25346920:0;chr18:25346921-25364355:-1;chr18:25364356-41469172:0;chr18:41469173-41506158:-1;chr18:41506159-57955333:0;chr18:57955334-57958028:-1;chr18:57958029-58699197:0;chr18:58699198-59400211:-1;chr18:59400212-67514625:0;chr18:67514626-67560274:-1;chr18:67560275-69724274:0;chr18:69724275-69748221:-1;chr18:69748222-71836356:0;chr18:71836357-72374290:1;chr18:72374291-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-106458599:0;chr2:106458600-106472719:-1;chr2:106472720-107840072:0;chr2:107840073-107844156:-1;chr2:107844157-108272722:0;chr2:108272723-108659332:-1;chr2:108659333-109212312:0;chr2:109212313-109619967:1;chr2:109619968-210277431:0;chr2:210277432-210296010:-1;chr2:210296011-243199373:0;chr3:0-49228709:0;chr3:109053894-109079026:-1;chr3:109079027-153531557:0;chr3:153531558-153978425:-1;chr3:153978426-163741830:0;chr3:163741831-163891620:-1;chr3:163891621-169679444:0;chr3:169679445-169689355:-1;chr3:169689356-198022430:0;chr3:49228710-49267487:-1;chr3:49228775-49255997:1;chr3:49267488-98434186:0;chr3:98434187-98435992:-1;chr3:98435993-109053893:0;chr4:0-121289445:0;chr4:121289446-121304044:-1;chr4:121304045-124230045:0;chr4:124230046-124231277:-1;chr4:124231278-128906043:0;chr4:128906044-128966498:1;chr4:128966499-129525077:0;chr4:129525078-129547283:-1;chr4:129547284-137001751:0;chr4:137001752-137003881:-1;chr4:137003882-137625342:0;chr4:137625343-137635236:-1;chr4:137635237-142150485:0;chr4:142150486-142159234:-1;chr4:142159235-143928982:0;chr4:143928983-144900884:1;chr4:144900885-151020719:0;chr4:151020720-151054739:-1;chr4:151054740-155468504:0;chr4:155468505-155471971:-1;chr4:155471972-155607363:0;chr4:155607364-155609080:-1;chr4:155609081-171792134:0;chr4:171792135-171818705:-1;chr4:171818706-191154276:0;chr5:0-23845131:0;chr5:121780185-121842398:-1;chr5:121842399-160941223:0;chr5:160941224-161669796:-1;chr5:161669797-180915260:0;chr5:23845132-24107310:1;chr5:24107311-36313159:0;chr5:36313160-36703057:-1;chr5:36703058-121780184:0;chr6:0-63591363:0;chr6:162801142-162847207:-1;chr6:162847208-171115067:0;chr6:63591364-63921040:-1;chr6:63921041-64876965:0;chr6:64876966-64881239:-1;chr6:64881240-82969369:0;chr6:82969370-83174555:-1;chr6:83174556-99028231:0;chr6:99028232-99052415:-1;chr6:99052416-162801141:0;chr7:0-127347573:0;chr7:127347574-127355073:-1;chr7:127355074-159138663:0;chr8:0-41751086:0;chr8:115791282-115817733:-1;chr8:115817734-138783580:0;chr8:138783581-138789341:-1;chr8:138789342-146364022:0;chr8:41751087-41807433:1;chr8:41807434-78121330:0;chr8:78121331-78123877:-1;chr8:78123878-78306063:0;chr8:78306064-79095536:1;chr8:79095537-79118543:0;chr8:79118544-79128660:-1;chr8:79128661-115791281:0;chr9:0-10917048:0;chr9:10917049-10924780:-1;chr9:10924781-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs18:72362175-72362175,hs18:72376179-72376179;hs4:142329799-142329799,hs4:143065118-143065118;hsX:94946411-94946411,hsX:112210871-112210871;hs11:21932378-21932378,hs11:24014675-24014675;hs22:17438287-17438287,hs22:44010955-44010955;hs8:30771358-30771358,hs22:43970168-43970168;hs4:129823364-129823364,hs4:129984528-129984528;hs11:100498098-100498098,hs11:127288184-127288184;hs4:172704269-172704269,hs4:174640570-174640570;hs4:173512318-173512318,hs4:179399701-179399701;hs3:160167460-160167460,hs3:167069212-167069212;hs18:51531327-51531327,hs18:52848651-52848651;hs2:109624155-109624155,hs5:160666711-160666711;hs18:67083922-67083922,hs18:67480569-67480569;hs3:4747703-4747703,hs3:5232308-5232308;hs6:119429584-119429584,hs6:120583146-120583146;hs8:30752095-30752095,hs11:72499460-72499460;hs11:104939763-104939763,hs11:127924865-127924865;hs22:17445249-17445249,hs22:43970155-43970155;hs2:56546059-56546059,hs2:57583126-57583126;hs4:176964567-176964567,hs4:178206461-178206461;hs6:120844966-120844966,hs6:162647796-162647796;hs4:172940942-172940942,hs4:181798939-181798939;hs4:176768441-176768441,hs4:182764133-182764133;hs5:18580870-18580870,hs5:18874050-18874050;hs11:73097744-73097744,hs22:37823376-37823376;hs1:101627881-101627881,hs1:103324647-103324647;hs3:11081178-11081178,hs3:160935438-160935438;hs4:171761094-171761094,hs4:181063940-181063940;hs6:119958937-119958937,hs6:127073463-127073463;hs8:78968808-78968808,hs8:86080461-86080461;hs11:100497997-100497997,hs11:101661950-101661950;hs15:41997395-41997395,hs17:30759467-30759467;hs1:194076105-194076105,hs1:198004530-198004530;hs3:2628047-2628047,hs18:65319601-65319601;hs2:56342631-56342631,hs2:92162655-92162655;hs3:1103155-1103155,hs3:11688381-11688381;hs4:171719187-171719187,hs4:172705866-172705866;hs4:178032306-178032306,hs4:181463886-181463886;hs3:5245051-5245051,hs3:11183973-11183973;hs4:142870785-142870785,hs4:144171100-144171100;hs4:177451890-177451890,hs4:182935891-182935891;hs5:118653325-118653325,hs5:119418153-119418153;hs8:78302716-78302716,hs8:86080129-86080129;hs11:101166806-101166806,hs11:103606056-103606056;hs11:102701310-102701310,hs11:102812355-102812355;hs4:121108689-121108689,hs4:121962371-121962371;hs6:127035346-127035346,hs6:162633368-162633368;hs11:127028622-127028622,hs11:127283360-127283360;hs2:106137004-106137004,hs2:109149413-109149413;hs3:4751985-4751985,hs3:11094485-11094485;hs3:11871793-11871793,hs3:31650486-31650486;hs3:13761916-13761916,hs3:49229959-49229959;hs5:20336593-20336593,hs5:21448412-21448412;hs6:83424297-83424297,hs6:84319032-84319032;hs18:63817276-63817276,hs18:64907218-64907218;hs1:96477937-96477937,hs1:99186022-99186022;hs4:32118436-32118436,hs4:45891378-45891378;hs4:175929855-175929855,hs4:179292187-179292187;hs6:84175480-84175480,hs6:125408056-125408056;hs6:83852981-83852981,hs6:124899967-124899967;hs8:30771136-30771136,hs22:37848949-37848949;hs9:28175579-28175579,hs9:29236772-29236772;hs19:39991336-39991336,hs19:40002004-40002004;hs1:75377332-75377332,hs1:96591076-96591076;hs3:144311124-144311124,hs3:146787850-146787850;hs4:33102878-33102878,hs4:35620668-35620668;hs4:121523026-121523026,hs4:121711235-121711235;hs6:119480238-119480238,hs6:120848710-120848710;hs11:97083354-97083354,hs11:127925744-127925744;hs11:99562785-99562785,hs11:100653081-100653081;hs11:100714423-100714423,hs11:104092361-104092361;hs18:38874621-38874621,hs18:43825221-43825221;hs18:58699871-58699871,hs18:68580439-68580439;hs18:61497926-61497926,hs18:66646483-66646483;hs2:90021076-90021076,hs9:12432808-12432808;hs3:160931469-160931469,hs3:162089682-162089682;hs6:68781529-68781529,hs6:123823863-123823863;hs6:80642295-80642295,hs6:124901768-124901768;hs11:101861343-101861343,hs11:103608977-103608977;hs11:97722799-97722799,hs11:101471897-101471897;hs3:147747399-147747399,hs18:63664378-63664378;hs4:128962610-128962610,hs4:130712413-130712413;hs4:179830414-179830414,hs4:181718940-181718940;hs4:116089041-116089041,hs4:182928275-182928275;hs5:21745562-21745562,hs5:81943551-81943551;hs5:160467124-160467124,hs5:161655186-161655186;hs6:63477638-63477638,hs6:97997097-97997097;hs8:78743479-78743479,hs8:86082337-86082337;hs18:65172330-65172330,hs18:65341265-65341265;hs18:39429406-39429406,hs18:43837973-43837973;hs2:115821304-115821304,hs2:155093764-155093764;hs3:1100398-1100398,hs3:11862654-11862654;hs3:1137402-1137402,hs3:11080681-11080681;hs3:160853972-160853972,hs3:163434540-163434540;hs4:120038478-120038478,hs4:182786993-182786993;hs4:121095560-121095560,hs4:121729136-121729136;hs5:18494996-18494996,hs5:23922366-23922366;hs5:121713256-121713256,hs7:121484681-121484681;hs6:82915353-82915353,hs6:84463621-84463621;hs9:11672230-11672230,hs9:12408117-12408117;hs11:98373963-98373963,hs11:127268477-127268477;hs18:71821938-71821938,hs18:72347808-72347808;hs1:195225218-195225218,hs1:196290109-196290109;hs2:30446271-30446271,hs2:92144461-92144461;hs2:56597148-56597148,hs2:57628762-57628762;hs2:90006695-90006695,hs9:10674990-10674990;hs3:11687588-11687588,hs3:49235713-49235713;hs3:108895475-108895475,hs3:111469624-111469624;hs4:172755074-172755074,hs4:172809514-172809514;hs4:172919258-172919258,hs4:181448733-181448733;hs4:173156915-173156915,hs4:178203483-178203483;hs4:33585982-33585982,hs4:45892555-45892555;hs5:21754095-21754095,hs5:23967006-23967006;hs11:97625965-97625965,hs11:127292284-127292284;hs2:108229212-108229212,hs2:108314380-108314380;hs3:2654068-2654068,hs3:11687005-11687005;hs4:176222802-176222802,hs4:178884897-178884897;hs6:83850727-83850727,hs6:84406272-84406272;hs18:38883407-38883407,hs18:42308757-42308757;hs19:27971368-27971368,hs19:34512447-34512447;hs2:109592156-109592156,hs5:162613576-162613576;hs3:3957232-3957232,hs18:61496521-61496521;hs3:11687616-11687616,hs18:72367713-72367713;hs4:134869436-134869436,hs4:136322654-136322654;hs4:176329141-176329141,hs4:176766049-176766049;hs6:98188963-98188963,hs6:99057509-99057509;hs6:119943698-119943698,hs6:127431014-127431014;hs6:98176185-98176185,hs6:99055879-99055879;hs1:195318197-195318197,hs1:197180514-197180514;hs4:33176489-33176489,hs4:45905916-45905916;hs5:20272704-20272704,hs5:22452878-22452878;hs6:119423591-119423591,hs6:120436366-120436366;hs8:78439841-78439841,hs8:78729798-78729798;hs8:78964795-78964795,hs8:86093022-86093022;hs11:100664998-100664998,hs11:102349085-102349085;hs4:116384730-116384730,hs4:182155162-182155162;hs4:174639509-174639509,hs4:178883069-178883069;hs5:19860331-19860331,hs5:21417850-21417850;hs11:21260076-21260076,hs11:29799109-29799109;hs11:97094959-97094959,hs11:100653149-100653149;hs11:97846666-97846666,hs11:102677177-102677177;hs11:99583278-99583278,hs11:102746717-102746717;hs11:102318120-102318120,hs11:128889255-128889255;hs15:43316977-43316977,hs19:39991764-39991764;hs18:59397213-59397213,hs18:68425351-68425351;hs4:116386450-116386450,hs4:176712697-176712697;hs4:121508570-121508570,hs4:121680079-121680079;hs4:131517678-131517678,hs4:134271472-134271472;hs5:18497495-18497495,hs5:19455700-19455700;hs5:18724513-18724513,hs5:24243978-24243978;hs5:18922784-18922784,hs5:20961030-20961030;hs18:63828852-63828852,hs18:67525474-67525474;hs3:98840418-98840418,hs18:62921968-62921968;hs4:127941932-127941932,hs4:131224680-131224680;hs5:119107061-119107061,hs5:121728947-121728947;hs5:119141272-119141272,hs7:125367936-125367936;hs8:78460368-78460368,hs8:79105132-79105132;hs9:28490636-28490636,hs9:32507213-32507213;hs3:162141329-162141329,hs3:163646506-163646506;hs4:129832100-129832100,hs4:131226410-131226410;hs6:70957422-70957422,hs6:126144050-126144050;hs6:80647453-80647453,hs6:124379672-124379672;hs22:36705082-36705082,hs22:37848552-37848552;hs2:108165809-108165809,hs5:162611619-162611619;hs11:98463829-98463829,hs11:101858473-101858473;hs11:22351726-22351726,hs11:32320771-32320771;hs2:56872776-56872776,hs2:57477891-57477891;hs3:31660918-31660918,hs3:49234681-49234681;hs3:1101919-1101919,hs3:11688403-11688403;hs11:28973440-28973440,hs11:32337331-32337331;hs15:43296274-43296274,hs17:28925349-28925349;hs18:67470100-67470100,hs18:67542551-67542551;hs3:3994947-3994947,hs3:11650922-11650922;hs3:160162016-160162016,hs3:164513018-164513018;hs4:144203631-144203631,hs4:144933058-144933058;hs4:128962665-128962665,hs4:128971338-128971338;hs4:172773046-172773046,hs4:181810359-181810359;hs9:11249661-11249661,hs9:43861060-43861060;hs6:120510463-120510463,hs6:126613786-126613786;hs7:91958778-91958778,hs7:92905012-92905012;hs11:97856223-97856223,hs11:104092069-104092069;hs13:111986142-111986142,hs21:39435875-39435875;hs18:39427828-39427828,hs18:43821668-43821668;hs2:105670542-105670542,hs2:108639545-108639545;hs2:109584825-109584825,hs5:160980195-160980195;hs4:172194012-172194012,hs4:173515462-173515462;hs4:177594009-177594009,hs4:178110811-178110811;hs2:57517000-57517000,hs2:57585302-57585302;hs13:53837072-53837072,hs13:55626737-55626737;hs1:70879442-70879442,hs17:38294340-38294340;hs5:21947682-21947682,hs5:83453344-83453344;hs9:11186886-11186886,hsY:13525687-13525687;hs1:97181571-97181571,hs13:55643358-55643358;hs5:19772415-19772415,hs5:21019981-21019981;hs6:156412728-156412728,hs17:81078444-81078444;hs12:113636483-113636483,hs20:19191557-19191557;hs16:78297430-78297430,hs16:81385406-81385406 ANK1;ANKIB1;ARHGAP32;ARHGAP42;C13orf16;C18orf25;C18orf55;C3orf31;C3orf66;C4orf29;C4orf31;CASC3;CASP1;CCDC102B;CCDC132;CCDC36;CCDC85A;CD226;CDH12;CDH18;CNTN4;CNTN5;CNTN6;COL9A1;CTH;DCLK2;DDX58;DLL3;DOK6;DOPEY1;DPP10;DPPA4;DSCR4;E2F5;EDAR;EDEM1;EDIL3;EFCAB6;ELFN2;ELOVL4;EYS;FAM184A;GAB4;GABRB2;GALNT13;GALNTL6;GAN;GPM6A;GYPB;HRH1;IBTK;INPP4B;IQCD;ITPR1;KCNT2;KIAA1377;LIMS1;LINGO2;LOC285375;LOC285501;LOC646498;LRRC37B2;MAP2;MGA;MMP12;MRPS9;MYH9;MYST3;NCK2;NCOA7;NELL1;NKAIN2;PARK2;PLCXD2;PLRG1;PRDM5;RELT;SCLT1;SEC62;SETBP1;SLC24A3;SLC6A1;SNAP91;SNCAIP;SND1;SNX7;SPATA5;STARD10;STT3B;TMEM123;TNFAIP8;TRDN;TRIM59;TRPC6;UBR1;VGLL4;WWOX;YAP1;ZBBX;ZNF330;ZNF407; Harvard Medical School, Boston, MA 02115, USA The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term chromoplexy, frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. GRCh37/hg19 phs000447 Yes ANK1,MYST3;C13orf16,DSCR4;C18orf55,ZNF407;C3orf31,STT3B;C3orf66,PLCXD2;CDH12,EDIL3;CNTN4,VGLL4;CNTN5,ARHGAP42;CNTN5,MMP12;CNTN6,SLC6A1;COL9A1,NCOA7;CTH,CASC3;DOK6,CD226;DOPEY1,NKAIN2;DOPEY1,SNAP91;DPP10,GALNT13;EDEM1,HRH1;ELOVL4,NKAIN2;GAB4,EFCAB6;ITPR1,EDEM1;LINGO2,DDX58;LOC100128164,SEC62;LOC285375,LOC646498;LOC646498,CCDC36;RELT,ELFN2;STT3B,CCDC36;TMEM123,ARHGAP32;TRIM59,ZBBX;UBR1,DLL3;UBR1,LRRC37B2;VGLL4,CCDC36;VGLL4,ZNF407;WWOX,GAN CTDB0277 Research 23622249 Baca SC, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, Van Allen E, Kryukov GV, Sboner A, Theurillat JP, Soong TD, Nickerson E, Auclair D, Tewari A, Beltran H, Onofrio RC, Boysen G, Guiducci C, Barbieri CE, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Ramos AH, Winckler W, Cipicchio M, Ardlie K, Kantoff PW, Berger MF, Gabriel SB, Golub TR, Meyerson M, Lander ES, Elemento O, Getz G, Demichelis F, Rubin MA, Garraway LA Punctuated evolution of prostate cancer genomes Cell 2013 Apr 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,18,20,21,X,Y Prostate cancer Next Generation Sequencing Homo sapiens PR-08-556 Illumina GAIIx chr10:0-26573287:0;chr10:26573288-26719060:-1;chr10:26719061-53382903:0;chr10:53382904-53584012:1;chr10:53584013-53869824:0;chr10:53869825-54214933:-1;chr10:54214934-54218726:0;chr10:54218727-54248647:-1;chr10:54248648-54592146:0;chr10:54592147-54593508:-1;chr10:54593509-83987398:0;chr10:83987399-84259822:-1;chr10:84259823-135534747:0;chr11:0-8138861:0;chr11:105726363-105752123:-1;chr11:105752124-109513696:0;chr11:109513697-109897305:-1;chr11:109897306-113019933:0;chr11:113019934-113677870:1;chr11:113677871-129592296:0;chr11:129592297-129605279:-1;chr11:129605280-133896589:0;chr11:133896590-134533060:-1;chr11:134533061-135006516:0;chr11:38130772-38146948:-1;chr11:38146949-55945078:0;chr11:55945079-55959621:-1;chr11:55959622-105726362:0;chr11:8138862-8322678:-1;chr11:8322679-38130771:0;chr12:0-17028027:0;chr12:17028028-17057837:-1;chr12:17057838-19274149:0;chr12:19274150-19276821:-1;chr12:19276822-40299976:0;chr12:40299977-40304618:-1;chr12:40304619-45527188:0;chr12:45527189-45560222:-1;chr12:45560223-46080636:0;chr12:46080637-46082970:-1;chr12:46082971-55086536:0;chr12:55086537-55087857:-1;chr12:55087858-96165170:0;chr12:96165171-96555786:-1;chr12:96555787-133851895:0;chr13:0-37730571:0;chr13:107454222-107465785:-1;chr13:107465786-113914511:0;chr13:113914512-113941631:-1;chr13:113941632-115169878:0;chr13:37730572-37830739:-1;chr13:37830740-63095898:0;chr13:63095899-63104105:-1;chr13:63104106-69031313:0;chr13:69031314-69041615:-1;chr13:69041616-107454221:0;chr14:0-22632197:0;chr14:22632198-22635370:-1;chr14:22635371-25293510:0;chr14:25293511-25294969:-1;chr14:25294970-28392253:0;chr14:28392254-28400077:-1;chr14:28400078-40063885:0;chr14:40063886-40091159:-1;chr14:40091160-41439838:0;chr14:41439839-41443981:-1;chr14:41443982-43211624:0;chr14:43211625-43269292:-1;chr14:43269293-44359857:0;chr14:44359858-44364895:-1;chr14:44364896-44549997:0;chr14:44549998-45012340:-1;chr14:45012341-84315258:0;chr14:84315259-84706371:-1;chr14:84706372-86667103:0;chr14:86667104-86692526:-1;chr14:86688659-86964186:1;chr14:86964187-107349540:0;chr15:0-22368180:0;chr15:22368181-22376357:-1;chr15:22376358-38228111:0;chr15:38228112-39088930:-1;chr15:39088931-92658465:0;chr15:92658466-92660632:-1;chr15:92660633-102531392:0;chr16:0-50858135:0;chr16:50858136-50859492:-1;chr16:50859493-53471627:0;chr16:53471628-53492709:-1;chr16:53492710-55075948:0;chr16:55075949-56052629:-1;chr16:56052630-56514808:0;chr16:56514809-56518191:-1;chr16:56518192-62319839:0;chr16:62319840-62326621:-1;chr16:62326622-64663758:0;chr16:64663759-64682855:-1;chr16:64682856-90354753:0;chr17:0-52835327:0;chr17:52835328-52842029:-1;chr17:52842030-81195210:0;chr18:0-5289866:0;chr18:22189488-22195099:-1;chr18:22195100-26716246:0;chr18:26716247-27040050:-1;chr18:26724603-27585868:1;chr18:27021639-27614652:-1;chr18:27614653-34746918:0;chr18:34746919-34751531:-1;chr18:34751532-35061350:0;chr18:35061351-35621514:-1;chr18:35621515-40804301:0;chr18:40804302-40916936:-1;chr18:40916937-59800153:0;chr18:5289867-5302154:-1;chr18:5302155-22189487:0;chr18:59800154-59802822:-1;chr18:59802823-64738426:0;chr18:64738427-64788676:1;chr18:64788677-67224463:0;chr18:67224464-67253175:-1;chr18:67253176-68095539:0;chr18:68095540-68232147:1;chr18:68232148-70414001:0;chr18:70414002-70823458:-1;chr18:70823459-73095347:0;chr18:73095348-73929553:-1;chr18:73344322-73809492:-1;chr18:73929554-74375357:0;chr18:74375358-74763946:-1;chr18:74763947-77319298:0;chr18:77319299-77322080:-1;chr18:77322081-78077248:0;chr19:0-50021623:0;chr19:50021624-50439892:1;chr19:50439893-59128983:0;chr1:0-89048546:0;chr1:105905624-105914722:-1;chr1:105914723-159125347:0;chr1:159125348-159564924:-1;chr1:159564925-193112763:0;chr1:193112764-193114686:-1;chr1:193114687-236985371:0;chr1:236985372-236993076:-1;chr1:236993077-239056310:0;chr1:239056311-239785949:1;chr1:239785950-249250621:0;chr1:89048547-89056731:-1;chr1:89056732-90578039:0;chr1:90578040-90580316:-1;chr1:90580317-93674820:0;chr1:93674821-94366888:-1;chr1:94366889-105905623:0;chr20:0-6717120:0;chr20:25905665-25907352:-1;chr20:25907353-63025520:0;chr20:6717121-7387992:-1;chr20:7083063-7124405:-1;chr20:7387993-25905664:0;chr21:0-10412536:0;chr21:10412537-10414320:-1;chr21:10414321-10789198:0;chr21:10789199-10817586:-1;chr21:10817587-39065585:0;chr21:39065586-39449152:-1;chr21:39449153-48129895:0;chr22:0-51304566:0;chr2:0-23666629:0;chr2:103933949-103935886:-1;chr2:103935887-105125257:0;chr2:105125258-105128527:-1;chr2:105128528-113113729:0;chr2:113113730-113479295:-1;chr2:113479296-115775491:0;chr2:115775492-116212158:-1;chr2:116212159-118028778:0;chr2:118028779-118178435:-1;chr2:118178436-140954945:0;chr2:140954946-140967493:-1;chr2:140967494-149634876:0;chr2:149634877-149654729:-1;chr2:149654730-155233473:0;chr2:155233474-156204443:-1;chr2:156204444-167192781:0;chr2:167192782-167205567:-1;chr2:167205568-185796873:0;chr2:185796874-185883031:-1;chr2:185883032-187556978:0;chr2:187556979-188442795:1;chr2:188442796-195423174:0;chr2:195423175-195439538:-1;chr2:195439539-199077246:0;chr2:199077247-199137931:-1;chr2:199137932-199171802:0;chr2:199171803-199173845:-1;chr2:199173846-211157083:0;chr2:211157084-211419121:-1;chr2:211419122-211684767:0;chr2:211684768-211687105:-1;chr2:211687106-243199373:0;chr2:23666630-23678053:-1;chr2:23678054-23905778:0;chr2:23905779-23912106:-1;chr2:23912107-24620046:0;chr2:24620047-24632894:-1;chr2:24632895-34809448:0;chr2:34809449-34826414:-1;chr2:34826415-56038858:0;chr2:56038859-56071238:-1;chr2:56071239-56566341:0;chr2:56566342-56847395:-1;chr2:56847396-58033930:0;chr2:58033931-58042201:-1;chr2:58042202-88770606:0;chr2:88770607-89585688:-1;chr2:89174298-89584986:1;chr2:89585689-95405091:0;chr2:95405092-95406533:-1;chr2:95406534-103933948:0;chr3:0-1340566:0;chr3:1340567-1342627:-1;chr3:1342628-7807923:0;chr3:135934084-135941639:-1;chr3:135941640-145506234:0;chr3:145506235-146275200:-1;chr3:145506989-146295527:1;chr3:146274146-146326952:-1;chr3:146326953-149921498:0;chr3:149921499-149925006:-1;chr3:149925007-160343494:0;chr3:160343495-161162976:-1;chr3:161162977-164917286:0;chr3:164917287-165732088:-1;chr3:165054967-165846159:-1;chr3:165846160-167936434:0;chr3:167936435-168654583:-1;chr3:168654584-190949458:0;chr3:190949459-191271098:-1;chr3:191271099-198022430:0;chr3:19432908-19501117:-1;chr3:19501118-78012704:0;chr3:78012705-78521252:-1;chr3:7807924-7818391:-1;chr3:7818392-19432907:0;chr3:78521253-81256323:0;chr3:81256324-81275847:-1;chr3:81275848-81611428:0;chr3:81611429-81613646:-1;chr3:81613647-83632088:0;chr3:83632089-83646835:-1;chr3:83646836-96155938:0;chr3:96155939-96200321:-1;chr3:96200322-97214262:0;chr3:97214263-97959602:1;chr3:97959603-135934083:0;chr4:0-12332809:0;chr4:105045882-105884173:-1;chr4:105884174-107532507:0;chr4:107532508-107533897:-1;chr4:107533898-117990631:0;chr4:117990632-118268478:-1;chr4:118114112-118495515:1;chr4:118239084-118528346:-1;chr4:118528347-120611574:0;chr4:120611575-120613892:-1;chr4:120613893-127509943:0;chr4:12332810-12750438:1;chr4:12342051-12904896:1;chr4:127509944-127531107:1;chr4:127531108-129449998:0;chr4:12904897-14936421:0;chr4:129449999-129461771:-1;chr4:129461772-129462002:0;chr4:129462003-129473712:-1;chr4:129473713-133476819:0;chr4:133476820-133479816:-1;chr4:133479817-142602659:0;chr4:142602660-142606483:-1;chr4:142606484-153785142:0;chr4:14936422-14997765:-1;chr4:14997766-45690242:0;chr4:153785143-153787808:-1;chr4:153787809-155627031:0;chr4:155627032-155645755:-1;chr4:155645756-162074571:0;chr4:162074572-162917851:-1;chr4:162917852-173219543:0;chr4:173219544-173962972:-1;chr4:173962973-174992295:0;chr4:174992296-175040627:-1;chr4:175040628-181481355:0;chr4:181481356-181482556:-1;chr4:181482557-191154276:0;chr4:45690243-45705317:-1;chr4:45705318-46148253:0;chr4:46148254-46164410:-1;chr4:46164411-60308052:0;chr4:60308053-60323644:-1;chr4:60323645-61274220:0;chr4:61274221-61286863:-1;chr4:61286864-63350484:0;chr4:63350485-63372779:-1;chr4:63372780-63632039:0;chr4:63632040-64102538:-1;chr4:63743748-63748217:-1;chr4:64102539-64489218:0;chr4:64489219-64786449:1;chr4:64786450-84885774:0;chr4:84885775-85380606:-1;chr4:84968370-85616299:1;chr4:85616300-105045881:0;chr5:0-1010840:0;chr5:1010841-1381697:1;chr5:105807706-106732325:-1;chr5:106732326-112992941:0;chr5:112992942-113004799:-1;chr5:113004800-149253578:0;chr5:1381698-7942020:0;chr5:149253579-149257657:-1;chr5:149257658-151974306:0;chr5:151974307-151976630:-1;chr5:151976631-170028127:0;chr5:170028128-170029404:-1;chr5:170029405-180915260:0;chr5:23030213-23036373:-1;chr5:23036374-24846703:0;chr5:24846704-25838516:-1;chr5:25838517-26010003:0;chr5:26010004-26330240:-1;chr5:26330241-105807705:0;chr5:7942021-7943825:-1;chr5:7943826-8654577:0;chr5:8654578-8877197:-1;chr5:8877198-23030212:0;chr6:0-48432489:0;chr6:127019711-127449672:-1;chr6:127449673-153837231:0;chr6:153837232-153911169:-1;chr6:153911170-156270351:0;chr6:156270352-156277218:-1;chr6:156277219-157616218:0;chr6:157616219-157743762:-1;chr6:157639664-157697325:1;chr6:157743763-159320916:0;chr6:159320917-159334261:-1;chr6:159334262-162146940:0;chr6:162146941-162161375:-1;chr6:162161376-164975418:0;chr6:164975419-164977116:-1;chr6:164977117-171115067:0;chr6:48432490-48434165:-1;chr6:48434166-49372809:0;chr6:49372810-50224190:1;chr6:50193201-50572058:1;chr6:50325681-50765786:1;chr6:50370460-51032611:-1;chr6:51032612-57956634:0;chr6:57956635-57959046:-1;chr6:57959047-64657089:0;chr6:64657090-64659433:-1;chr6:64659434-65059147:0;chr6:65059148-65061026:-1;chr6:65061027-65254947:0;chr6:65254948-65302176:1;chr6:65302177-65500541:0;chr6:65500542-65505073:-1;chr6:65505074-84600803:0;chr6:84600804-85474968:-1;chr6:85474969-127019710:0;chr7:0-34217492:0;chr7:108777630-108781090:-1;chr7:108781091-109120821:0;chr7:109120822-109123092:-1;chr7:109123093-118990540:0;chr7:118990541-119206700:-1;chr7:119206701-119707243:0;chr7:119707244-119938720:1;chr7:119938721-120302439:0;chr7:120302440-120303984:-1;chr7:120303985-124564948:0;chr7:124564949-124572845:-1;chr7:124572846-125661096:0;chr7:125661097-125677534:1;chr7:125677535-127389265:0;chr7:127389266-127399153:-1;chr7:127399154-147857115:0;chr7:147857116-147864255:-1;chr7:147864256-159073249:0;chr7:159073250-159074788:-1;chr7:159074789-159138663:0;chr7:34217493-34219551:-1;chr7:34219552-34492796:0;chr7:34492797-34494132:-1;chr7:34494133-35295967:0;chr7:35295968-35483532:-1;chr7:35483533-35602525:0;chr7:35602526-35616971:-1;chr7:35616972-35662029:0;chr7:35662030-35972660:1;chr7:35972661-37244655:0;chr7:37244656-37245937:-1;chr7:37245938-37437208:0;chr7:37437209-37458890:-1;chr7:37458891-37554394:0;chr7:37554395-37556133:-1;chr7:37556134-37682746:0;chr7:37682747-38576951:-1;chr7:37709363-38501582:-1;chr7:37728441-38557806:1;chr7:37791145-38651921:1;chr7:37812225-38765345:1;chr7:37835640-38767616:-1;chr7:38082699-38092329:-1;chr7:38636972-38849681:1;chr7:38753290-38944097:-1;chr7:38944098-40103083:0;chr7:40103084-40120042:-1;chr7:40120043-40152734:0;chr7:40152735-40162625:-1;chr7:40162626-46064581:0;chr7:46064582-46071710:-1;chr7:46071711-46304907:0;chr7:46304908-46371530:-1;chr7:46371531-48415840:0;chr7:48415841-48440512:-1;chr7:48440513-48616261:0;chr7:48616262-48898306:-1;chr7:48631160-49494306:1;chr7:48771879-49542684:1;chr7:49542685-52741440:0;chr7:52741441-52743687:-1;chr7:52743688-82235628:0;chr7:82235629-82249196:-1;chr7:82249197-82249960:0;chr7:82249961-82252725:-1;chr7:82252726-108777629:0;chr8:0-16847597:0;chr8:112477379-112480677:-1;chr8:112480678-114869522:0;chr8:114869523-115243364:1;chr8:115243365-146364022:0;chr8:16847598-16934826:-1;chr8:16934827-31321382:0;chr8:31321383-31323011:-1;chr8:31323012-33673616:0;chr8:33673617-33684091:-1;chr8:33684092-62700363:0;chr8:62700364-62712261:-1;chr8:62712262-63482193:0;chr8:63482194-63503910:-1;chr8:63503911-72836551:0;chr8:72836552-72855373:-1;chr8:72855374-88152250:0;chr8:88152251-89075183:1;chr8:89075184-89505830:0;chr8:89505831-89507259:-1;chr8:89507260-112477378:0;chr9:0-201255:0;chr9:105865506-105909640:-1;chr9:105909641-106172353:0;chr9:106172354-106176921:-1;chr9:106176922-106239241:0;chr9:106239242-106273203:-1;chr9:106273204-141213431:0;chr9:1160184-5076878:0;chr9:201256-1160183:-1;chr9:29902323-29919903:-1;chr9:29919904-30681411:0;chr9:30681412-30691135:-1;chr9:30691136-31911693:0;chr9:31911694-32438785:-1;chr9:32438786-33577752:0;chr9:33577753-33614435:-1;chr9:33614436-33614988:0;chr9:33614989-33621290:-1;chr9:33621291-69116666:0;chr9:5076879-5144972:-1;chr9:5144973-5395972:0;chr9:5395973-5892180:-1;chr9:5892181-6418108:0;chr9:6418109-6438804:-1;chr9:6438805-29902322:0;chr9:69116667-69118012:-1;chr9:69118013-74030682:0;chr9:74030683-74040910:-1;chr9:74040911-105865505:0;chrX:0-86639042:0;chrX:124167990-124169139:-1;chrX:124169140-143153190:0;chrX:143153191-143594535:-1;chrX:143594536-146356645:0;chrX:146356646-146358913:-1;chrX:146358914-155270560:0;chrX:86639043-87182530:-1;chrX:86639395-87181026:1;chrX:87182531-87788822:0;chrX:87788823-88647260:-1;chrX:88584275-88599768:-1;chrX:88647261-124167989:0;chrY:0-4620525:0;chrY:4620526-4885990:-1;chrY:4638007-5016407:1;chrY:4871931-5634162:-1;chrY:5634163-59373566:0 hs18:63249896-63249896,hs18:72468761-72468761;hs18:34683679-34683679,hs18:40452287-40452287;hs18:40264943-40264943,hs18:74396772-74396772;hs8:118427993-118427993,hs8:119359519-119359519;hs7:45842231-45842231,hs7:50235593-50235593;hsX:71259946-71259946,hsX:73315764-73315764;hs9:5004416-5004416,hs9:14340508-14340508;hs12:43542154-43542154,hs12:45437511-45437511;hs3:162079255-162079255,hs3:163830586-163830586;hs2:59970889-59970889,hs2:60178321-60178321;hs12:18100340-18100340,hs12:18518466-18518466;hs5:6320437-6320437,hs5:25881569-25881569;hs2:125575868-125575868,hs5:4803941-4803941;hs6:65853400-65853400,hs6:152777103-152777103;hs12:124455936-124455936,hs18:36361576-36361576;hs18:70862551-70862551,hs18:73357937-73357937;hs13:83702775-83702775,hs13:84750796-84750796;hs18:34958329-34958329,hs18:38260102-38260102;hs18:70873758-70873758,hs18:75899254-75899254;hs1:150382800-150382800,hs1:150413192-150413192;hs3:763001-763001,hs3:1381427-1381427;hs6:64230922-64230922,hs6:152787966-152787966;hs18:70645168-70645168,hs18:74705289-74705289;hsX:143154207-143154207,hsX:144359795-144359795;hs3:157635364-157635364,hs3:160985615-160985615;hs4:177490991-177490991,hs4:178815373-178815373;hs4:178814904-178814904,hs4:179612671-179612671;hs5:137491277-137491277,hs5:140069250-140069250;hs7:37694209-37694209,hs7:39094376-39094376;hs8:114124957-114124957,hs8:115049488-115049488;hs18:35031389-35031389,hs18:39432198-39432198;hs18:35582691-35582691,hs18:35716857-35716857;hs2:138800988-138800988,hs2:140275375-140275375;hs5:456577-456577,hs5:2545950-2545950;hs6:153159061-153159061,hs6:154814073-154814073;hs8:114727553-114727553,hs8:119310775-119310775;hs18:64762074-64762074,hs18:75327022-75327022;hs18:40436493-40436493,hs18:72499841-72499841;hs20:7651594-7651594,hs20:11924731-11924731;hs2:116845976-116845976,hs2:117096986-117096986;hs2:139734998-139734998,hs2:140161915-140161915;hs3:3250562-3250562,hs3:4619731-4619731;hs7:49417793-49417793,hs7:52792220-52792220;hs7:119308481-119308481,hs20:11586758-11586758;hs7:120160374-120160374,hs20:11708238-11708238;hs12:16254146-16254146,hs12:18438341-18438341;hs18:34954370-34954370,hs18:37639255-37639255;hs18:64738402-64738402,hs18:71076237-71076237;hs18:35031908-35031908,hs18:39571281-39571281;hs2:122947305-122947305,hs5:3411391-3411391;hs4:175204952-175204952,hs4:175648990-175648990;hs5:25837474-25837474,hs5:25928216-25928216;hs6:85923502-85923502,hs6:97284074-97284074;hs7:36848529-36848529,hs7:37635597-37635597;hs7:37811437-37811437,hs7:38613727-38613727;hs7:49717482-49717482,hs7:52733647-52733647;hs11:109078180-109078180,hs11:128751795-128751795;hs18:40509514-40509514,hs18:63298852-63298852;hs18:64739624-64739624,hs18:73599595-73599595;hs2:127362157-127362157,hs5:17939728-17939728;hs3:165407318-165407318,hs3:167093188-167093188;hs4:172152040-172152040,hs4:172850283-172850283;hs4:20154401-20154401,hs4:23117836-23117836;hs4:118478187-118478187,hs8:131834669-131834669;hs5:10332248-10332248,hs5:13949167-13949167;hs7:120250835-120250835,hs20:11706155-11706155;hs9:27310076-27310076,hs9:126203635-126203635;hs12:7724975-7724975,hs12:9153095-9153095;hs18:38404589-38404589,hs18:39892207-39892207;hs18:39376849-39376849,hs18:73320909-73320909;hs18:40849409-40849409,hs18:75140957-75140957;hs18:66262838-66262838,hs18:73809533-73809533;hs18:63245700-63245700,hs18:73884128-73884128;hs20:12709441-12709441,hs20:13057471-13057471;hsX:71255349-71255349,hsX:73313573-73313573;hs2:138187786-138187786,hs2:139417366-139417366;hs2:113113784-113113784,hs2:115252459-115252459;hs5:590486-590486,hs5:2556011-2556011;hs6:153224019-153224019,hs6:154337204-154337204;hs8:113871693-113871693,hs8:116976894-116976894;hs10:9358670-9358670,hs10:11246973-11246973;hs12:14108704-14108704,hs12:18792134-18792134;hs13:83427848-83427848,hs13:86206478-86206478;hs18:35303029-35303029,hs18:72970317-72970317;hs18:40524961-40524961,hs18:64950736-64950736;hs18:63221562-63221562,hs18:66774742-66774742;hs18:70294689-70294689,hs18:73362415-73362415;hs18:35427408-35427408,hs18:75112267-75112267;hs18:40312910-40312910,hs18:71145897-71145897;hs2:57893438-57893438,hs2:60211616-60211616;hs2:108143532-108143532,hs2:140782509-140782509;hs2:123939178-123939178,hs2:125739006-125739006;hs2:138987830-138987830,hs2:140118852-140118852;hs2:56957965-56957965,hs2:57584531-57584531;hs3:431210-431210,hs3:1381408-1381408;hs3:16519450-16519450,hs3:85862976-85862976;hs3:165373870-165373870,hs3:166052898-166052898;hs4:177495751-177495751,hs4:179615522-179615522;hs6:157172019-157172019,hs6:157880226-157880226;hs6:50168152-50168152,hs6:50272785-50272785;hs7:39042399-39042399,hs7:40471765-40471765;hs7:48804427-48804427,hs7:49004215-49004215;hs9:105858499-105858499,hs9:106762490-106762490;hs10:52883741-52883741,hs10:54213960-54213960;hs14:44959011-44959011,hs14:45367857-45367857;hs18:39151992-39151992,hs18:67596930-67596930;hs20:9886153-9886153,hs20:12510676-12510676;hs1:150381536-150381536,hs1:152209203-152209203;hs2:53545510-53545510,hs2:55466468-55466468;hs2:54071774-54071774,hs2:56614771-56614771;hs2:138620727-138620727,hs2:139955489-139955489;hs2:138610272-138610272,hs2:139909131-139909131;hs2:57891950-57891950,hs2:60208180-60208180;hs3:17693618-17693618,hs3:85167908-85167908;hs3:165056351-165056351,hs3:166260239-166260239;hs4:117364950-117364950,hs8:131894716-131894716;hs5:25929241-25929241,hs5:26694734-26694734;hs6:48304481-48304481,hs6:50996347-50996347;hs6:85487410-85487410,hs6:85745158-85745158;hs6:85615666-85615666,hs6:154758001-154758001;hs6:123477294-123477294,hs6:126722534-126722534;hs7:37506636-37506636,hs7:37778297-37778297;hs7:37708776-37708776,hs7:39033100-39033100;hs7:47935069-47935069,hs7:49428675-49428675;hs8:114708794-114708794,hs8:117075772-117075772;hs8:116265646-116265646,hs8:118309651-118309651;hs8:114864122-114864122,hs8:119312690-119312690;hs9:12794532-12794532,hs9:15623739-15623739;hs12:43130669-43130669,hs12:45418881-45418881;hs18:66546788-66546788,hs18:71147460-71147460;hs18:31147805-31147805,hs18:32726913-32726913;hs18:36716244-36716244,hs18:70093287-70093287;hs2:25769146-25769146,hs2:25771143-25771143;hs2:59954263-59954263,hs2:60169303-60169303;hs2:187679366-187679366,hs2:191015697-191015697;hs3:160937428-160937428,hs3:162455666-162455666;hs3:161312546-161312546,hs3:162853282-162853282;hs3:165374510-165374510,hs3:167094186-167094186;hs3:78466138-78466138,hs3:82699512-82699512;hs3:18955777-18955777,hs6:57451578-57451578;hs4:162075685-162075685,hs4:162924643-162924643;hs4:117183405-117183405,hs8:131918494-131918494;hs4:117321611-117321611,hs8:131834779-131834779;hs5:4240958-4240958,hs5:83633565-83633565;hs6:57362594-57362594,hs6:65882759-65882759;hs7:36305099-36305099,hs7:39147090-39147090;hs7:48221689-48221689,hs7:48830335-48830335;hs7:145349053-145349053,hs7:146390054-146390054;hs8:114984337-114984337,hs8:117977710-117977710;hs8:119331609-119331609,hs8:123112478-123112478;hs10:53577889-53577889,hs10:54173735-54173735;hs12:17416785-17416785,hs12:18820311-18820311;hs16:25957978-25957978,hs16:29212675-29212675;hs18:31126624-31126624,hs18:32723928-32723928;hs18:31961406-31961406,hs18:32533348-32533348;hs18:38550401-38550401,hs18:70616690-70616690;hs18:66546804-66546804,hs18:73788878-73788878;hs18:68346924-68346924,hs18:69233358-69233358;hsX:143589606-143589606,hsX:144358899-144358899;hs2:57313899-57313899,hs2:62774390-62774390;hs3:165719647-165719647,hs3:166053370-166053370;hs3:82999236-82999236,hs3:83116231-83116231;hs4:28448263-28448263,hs4:28450031-28450031;hs4:110159960-110159960,hs4:126694814-126694814;hs4:175626517-175626517,hs4:177020242-177020242;hs5:97904988-97904988,hs5:102375199-102375199;hs5:137489025-137489025,hs5:140055398-140055398;hs5:166608363-166608363,hs5:167110778-167110778;hs6:50046063-50046063,hs6:50608683-50608683;hs7:35685220-35685220,hs7:39220519-39220519;hs7:37384162-37384162,hs7:40474913-40474913;hs8:87848426-87848426,hs8:89075789-89075789;hs8:114896634-114896634,hs8:122954313-122954313;hs8:118352985-118352985,hs8:122976545-122976545;hs11:108594311-108594311,hs13:21728539-21728539;hs13:83427587-83427587,hs13:86199909-86199909;hs18:39159198-39159198,hs18:67639085-67639085;hs18:64796022-64796022,hs18:64974479-64974479;hs18:73602077-73602077,hs18:73808001-73808001;hs21:37543913-37543913,hs21:38843985-38843985;hs1:238147421-238147421,hs1:239528072-239528072;hs2:56945570-56945570,hs2:57365844-57365844;hs3:16518548-16518548,hs3:85187943-85187943;hs4:174384264-174384264,hs4:174394240-174394240;hs5:103511717-103511717,hs5:104935497-104935497;hs5:141121412-141121412,hs5:141560961-141560961;hs5:10331388-10331388,hs5:13506284-13506284;hs6:156334789-156334789,hs6:157777049-157777049;hs7:35682244-35682244,hs7:38964122-38964122;hs7:120248777-120248777,hs20:12995823-12995823;hs7:119292123-119292123,hs20:11924902-11924902;hs8:116944275-116944275,hs8:117927717-117927717;hs10:52481641-52481641,hs10:52615622-52615622;hs11:97739476-97739476,hs11:98104136-98104136;hs12:8230977-8230977,hs12:9769238-9769238;hs16:25993563-25993563,hs16:32611005-32611005;hs18:39730688-39730688,hs18:70974047-70974047;hs18:58658528-58658528,hs18:63135827-63135827;hs18:35091906-35091906,hs18:70093526-70093526;hsX:87074869-87074869,hsX:88628852-88628852;hs2:163921494-163921494,hs2:165275698-165275698;hs3:158760476-158760476,hs3:162424515-162424515;hs3:78047867-78047867,hs11:98191139-98191139;hs4:172166533-172166533,hs4:172851034-172851034;hs4:175165014-175165014,hs4:175955004-175955004;hs7:38961009-38961009,hs7:39192301-39192301;hs7:43437497-43437497,hs7:52989227-52989227;hs7:48539543-48539543,hs7:49578671-49578671;hs11:8160217-8160217,hs11:8645089-8645089;hs12:7725500-7725500,hs12:8960258-8960258;hs14:39015572-39015572,hs14:45351623-45351623;hs14:52625014-52625014,hs14:54971046-54971046;hs16:59766124-59766124,hs16:64664158-64664158;hs18:40804538-40804538,hs18:63181705-63181705;hs18:69229520-69229520,hs18:69254669-69254669;hs2:53575843-53575843,hs2:55472424-55472424;hs4:162916709-162916709,hs4:162924262-162924262;hs5:8816659-8816659,hs5:11967188-11967188;hs5:9281213-9281213,hs5:11958635-11958635;hs5:108009605-108009605,hs5:112585921-112585921;hs6:50250301-50250301,hs6:50817409-50817409;hs6:63083078-63083078,hs6:64102987-64102987;hs6:64346198-64346198,hs6:155817351-155817351;hs7:46340654-46340654,hs7:47927418-47927418;hs7:48294776-48294776,hs7:48841220-48841220;hs7:36846799-36846799,hs7:38757994-38757994;hs7:38559028-38559028,hs7:38703882-38703882;hs9:2548720-2548720,hs9:7946397-7946397;hs9:73198401-73198401,hs9:73647485-73647485;hs9:105784120-105784120,hs9:106708177-106708177;hs10:54503468-54503468,hs10:108875365-108875365;hs16:56475899-56475899,hs16:56516736-56516736;hs20:4313341-4313341,hs20:13533168-13533168;hs20:9924147-9924147,hs20:12526347-12526347;hs1:238149392-238149392,hs1:239538279-239538279;hs3:116835246-116835246,hs3:118333657-118333657;hs3:154179948-154179948,hs3:158368691-158368691;hs3:166885068-166885068,hs3:171170577-171170577;hs3:166885148-166885148,hs3:171170673-171170673;hs3:164487223-164487223,hs3:165812148-165812148;hs4:85329786-85329786,hs4:86578617-86578617;hs4:180003422-180003422,hs4:181052342-181052342;hs6:57362756-57362756,hs6:64257068-64257068;hs6:156763095-156763095,hs6:157620854-157620854;hs6:165385986-165385986,hs6:167156639-167156639;hs7:48202605-48202605,hs7:48684069-48684069;hs7:48263498-48263498,hs7:48808222-48808222;hs7:33900150-33900150,hs7:39076465-39076465;hs8:116288303-116288303,hs8:118344739-118344739;hs9:33765026-33765026,hs9:33843845-33843845;hs11:56654292-56654292,hs11:58326859-58326859;hs12:94559002-94559002,hs12:96165208-96165208;hs2:25769114-25769114,hs2:25770972-25770972;hs2:53546779-53546779,hs2:53575847-53575847;hs4:110174539-110174539,hs4:126700132-126700132;hs4:115077683-115077683,hs4:116371595-116371595;hs4:174377841-174377841,hs4:174395227-174395227;hs5:10560918-10560918,hs5:13144953-13144953;hs5:24861352-24861352,hs5:26671514-26671514;hs7:33904085-33904085,hs7:35989057-35989057;hs7:48738030-48738030,hs7:49006470-49006470;hs7:48751103-48751103,hs7:49587891-49587891;hs7:49495171-49495171,hs7:52791598-52791598;hs7:50430918-50430918,hs7:52990012-52990012;hs9:73199976-73199976,hs9:73648044-73648044;hs10:16089976-16089976,hs10:18303488-18303488;hs10:50497358-50497358,hs10:52787848-52787848;hs18:35223164-35223164,hs18:66546295-66546295;hs18:67273327-67273327,hs18:69199752-69199752;hs20:4344628-4344628,hs20:16267652-16267652;hs20:5651097-5651097,hs20:11853341-11853341;hs20:7478929-7478929,hs20:13526050-13526050;hsX:147790763-147790763,hsX:148986465-148986465;hs1:93966540-93966540,hs1:96214289-96214289;hs1:94022998-94022998,hs1:96205849-96205849;hs4:85536111-85536111,hs4:86568287-86568287;hs4:181369618-181369618,hs4:181675006-181675006;hs5:107926227-107926227,hs5:110703578-110703578;hs6:155020785-155020785,hs6:157958183-157958183;hs6:64581788-64581788,hs6:157187899-157187899;hs7:35639452-35639452,hs7:37432360-37432360;hs7:48839905-48839905,hs7:49663699-49663699;hs7:119869433-119869433,hs7:119940615-119940615;hs9:1664846-1664846,hs9:5079148-5079148;hs10:16068373-16068373,hs10:18303452-18303452;hs11:39094974-39094974,hs11:43114714-43114714;hs11:39283267-39283267,hs11:43156613-43156613;hs12:9151447-9151447,hs12:9768454-9768454;hs12:10286905-10286905,hs12:15034657-15034657;hs12:127556188-127556188,hs18:36573961-36573961;hs18:34713225-34713225,hs18:71147371-71147371;hs18:35254043-35254043,hs18:75802347-75802347;hs18:67075178-67075178,hs18:70483499-70483499;hs18:68936983-68936983,hs18:70528834-70528834;hsX:85599030-85599030,hsX:87089824-87089824;hs2:163920683-163920683,hs2:164975001-164975001;hs3:164500098-164500098,hs3:165705260-165705260;hs3:164924603-164924603,hs3:166284316-166284316;hs3:82759799-82759799,hs3:83329806-83329806;hs4:85467581-85467581,hs4:86225687-86225687;hs5:103372169-103372169,hs5:106777474-106777474;hs6:49371625-49371625,hs6:51623092-51623092;hs7:36368527-36368527,hs7:39131778-39131778;hs7:47312937-47312937,hs7:52352784-52352784;hs7:48882620-48882620,hs7:52733060-52733060;hs7:36412001-36412001,hs7:38559580-38559580;hs9:3704680-3704680,hs9:5893264-5893264;hs9:7120637-7120637,hs9:10457635-10457635;hs9:201266-201266,hs9:5449906-5449906;hs11:113027691-113027691,hs11:113682280-113682280;hs12:94561601-94561601,hs12:96532954-96532954;hs15:33519941-33519941,hs15:35368891-35368891;hs16:47740586-47740586,hs16:53460337-53460337;hs16:55110277-55110277,hs16:56501351-56501351;hs18:63570580-63570580,hs18:66312791-66312791;hs18:73238486-73238486,hs18:73977501-73977501;hsX:147811457-147811457,hsX:149082362-149082362;hs4:85723997-85723997,hs4:86571801-86571801;hs4:189542984-189542984,hsY:23231747-23231747;hs5:462484-462484,hs5:619329-619329;hs6:155818302-155818302,hs6:157748611-157748611;hs7:119704515-119704515,hs7:120060033-120060033;hs7:120064346-120064346,hs20:12672900-12672900;hs7:120145634-120145634,hs20:12445816-12445816;hs9:678820-678820,hs9:7284765-7284765;hs9:3361261-3361261,hs9:6245605-6245605;hs9:3681131-3681131,hs9:7351563-7351563;hs9:5152919-5152919,hs9:5867257-5867257;hs10:52482999-52482999,hs10:54504662-54504662;hs12:127522194-127522194,hs18:38175045-38175045;hs15:33785744-33785744,hs15:35855536-35855536;hs16:47739518-47739518,hs16:56020143-56020143;hs18:67095251-67095251,hs18:68348815-68348815;hs18:68835663-68835663,hs18:70006486-70006486;hs18:25601589-25601589,hs22:29065933-29065933;hs20:4914743-4914743,hs20:13069011-13069011;hs20:4958869-4958869,hs20:7441781-7441781;hs20:5448643-5448643,hs20:7524804-7524804;hs20:5649937-5649937,hs20:11893476-11893476;hs2:103846194-103846194,hs2:139057972-139057972;hs9:202032-202032,hs9:5991262-5991262;hs9:5364066-5364066,hs9:10033124-10033124;hs9:7118770-7118770,hs9:9119358-9119358;hs11:38150468-38150468,hs11:39313523-39313523;hs14:50470970-50470970,hs14:53746900-53746900;hs16:51415678-51415678,hs16:56463631-56463631;hs16:75543978-75543978,hs21:20941033-20941033;hs18:35731428-35731428,hs18:69530767-69530767;hs18:69261441-69261441,hs18:69752643-69752643;hs1:94005487-94005487,hs1:94103906-94103906;hs2:89173090-89173090,hs2:89391449-89391449;hs2:113478908-113478908,hs2:115250625-115250625;hs5:106444664-106444664,hs5:110685036-110685036;hs5:141017906-141017906,hs5:141560729-141560729;hs6:66937836-66937836,hs6:123889897-123889897;hs7:43408999-43408999,hs7:48554197-48554197;hs7:47355127-47355127,hs7:52354157-52354157;hs7:113331306-113331306,hs7:120837183-120837183;hs8:88151510-88151510,hs8:88358752-88358752;hs9:1157819-1157819,hs9:14339454-14339454;hs9:1185874-1185874,hs9:5896680-5896680;hs9:1606234-1606234,hs9:4577200-4577200;hs11:8293351-8293351,hs11:8637173-8637173;hs11:56653639-56653639,hs11:58325480-58325480;hs16:59446142-59446142,hs16:62327935-62327935;hs16:75544297-75544297,hs21:20938465-20938465;hs18:35926703-35926703,hs18:68499249-68499249;hs18:66255425-66255425,hs18:72861979-72861979;hs20:6720497-6720497,hs20:13070006-13070006;hs2:122935927-122935927,hs5:4221272-4221272;hs4:85479267-85479267,hs4:86061507-86061507;hs7:48249276-48249276,hs7:50518306-50518306;hs7:48252422-48252422,hs7:50277194-50277194;hs9:5249168-5249168,hs9:7194358-7194358;hs9:2303901-2303901,hs9:10535997-10535997;hs10:52671618-52671618,hs18:65057631-65057631;hs13:48801014-48801014,hs13:48954069-48954069;hs18:36723414-36723414,hs18:37827732-37827732;hs18:68527357-68527357,hs18:69579353-69579353;hs18:70008265-70008265,hs18:70526041-70526041;hs2:89399439-89399439,hs2:112635212-112635212;hs4:180324817-180324817,hs4:181952942-181952942;hs5:1048201-1048201,hs5:1080892-1080892;hs5:8680913-8680913,hs5:10583844-10583844;hs7:35066123-35066123,hs7:39050369-39050369;hs8:114160150-114160150,hs8:121952576-121952576;hs9:11213104-11213104,hs9:15624223-15624223;hs9:5893429-5893429,hs9:7114260-7114260;hs10:115386468-115386468,hs10:116826540-116826540;hs12:127547178-127547178,hs18:68159162-68159162;hs14:52569020-52569020,hs14:52578690-52578690;hs18:36529229-36529229,hs18:69305983-69305983;hs18:64027467-64027467,hs18:66545282-66545282;hs1:186332523-186332523,hs1:186335969-186335969;hs2:186147797-186147797,hs2:187757798-187757798;hs2:213494239-213494239,hs2:213541096-213541096;hs2:122935914-122935914,hs5:4221106-4221106;hs4:85636055-85636055,hs4:85817192-85817192;hs4:181949012-181949012,hsY:23231581-23231581;hs5:7276030-7276030,hs5:24412141-24412141;hs5:166608553-166608553,hs5:167110884-167110884;hs5:1048749-1048749,hs5:1081962-1081962;hs6:82919632-82919632,hs6:153574894-153574894;hs7:51765995-51765995,hs7:52133248-52133248;hs9:9865665-9865665,hs9:14307572-14307572;hs9:33576205-33576205,hs9:33581200-33581200;hs11:113016491-113016491,hs11:113026529-113026529;hs13:48801564-48801564,hs13:48954148-48954148;hs14:86692477-86692477,hs14:87522511-87522511;hs15:20626409-20626409,hs15:22581788-22581788;hs18:34688801-34688801,hs18:34713277-34713277;hs1:238241145-238241145,hs1:239452035-239452035;hs5:9253151-9253151,hs5:13128315-13128315;hs5:103411361-103411361,hs5:108332272-108332272;hs6:82586641-82586641,hs6:84432544-84432544;hs7:35153750-35153750,hs7:36303075-36303075;hs7:49054848-49054848,hs7:52138103-52138103;hs7:52008491-52008491,hs7:52971682-52971682;hs7:120159728-120159728,hs20:12681510-12681510;hs9:3361976-3361976,hs9:5173458-5173458;hs9:4371714-4371714,hs9:10795060-10795060;hs12:38878335-38878335,hs12:40306560-40306560;hs12:40469365-40469365,hs12:77023404-77023404;hs12:126498481-126498481,hs18:68127545-68127545;hs18:21366991-21366991,hs18:22584716-22584716;hsX:62288766-62288766,hsX:63703987-63703987;hs1:94017748-94017748,hs1:94023098-94023098;hs1:238244945-238244945,hs1:239667822-239667822;hs1:215660065-215660065,hs7:128679848-128679848;hs2:87101649-87101649,hs2:89399439-89399439;hs3:17882632-17882632,hs3:86219534-86219534;hs3:79627566-79627566,hs3:80566731-80566731;hs4:16305995-16305995,hs4:19334446-19334446;hs4:66390539-66390539,hs4:69788345-69788345;hs4:189565968-189565968,hs4:189780924-189780924;hs4:190428735-190428735,hs4:190442610-190442610;hs5:130550535-130550535,hs12:22257858-22257858;hs7:36193274-36193274,hs7:37370545-37370545;hs7:48293849-48293849,hs7:49424650-49424650;hs7:49058505-49058505,hs7:52158403-52158403;hs7:49370410-49370410,hs7:52226964-52226964;hs7:52040940-52040940,hs7:55754492-55754492;hs7:52905297-52905297,hs7:52967793-52967793;hs7:53392672-53392672,hs7:56480012-56480012;hs7:113831980-113831980,hs7:125410702-125410702;hs7:118747500-118747500,hs7:124523875-124523875;hs7:120854068-120854068,hs7:125396270-125396270;hs9:12738133-12738133,hs9:14301108-14301108;hs10:112860997-112860997,hs10:117881737-117881737;hs10:116284711-116284711,hs10:119948575-119948575;hs10:108870485-108870485,hs18:65057403-65057403;hs11:24031582-24031582,hs11:26126766-26126766;hs12:38873730-38873730,hs12:40434909-40434909;hs15:39069911-39069911,hs15:39264764-39264764;hs16:51440838-51440838,hs16:56095828-56095828;hs16:75620562-75620562,hs16:75912415-75912415;hsX:116496311-116496311,hsX:117624592-117624592;hs1:191867971-191867971,hs1:193309957-193309957;hs1:239450733-239450733,hs1:239665745-239665745;hs2:122677165-122677165,hs5:121896351-121896351;hs3:81083009-81083009,hs3:84003184-84003184;hs3:146528078-146528078,hs3:146774394-146774394;hs3:76647663-76647663,hs3:76672125-76672125;hs4:15175385-15175385,hs4:18005642-18005642;hs4:111882953-111882953,hs4:112221487-112221487;hs4:119774922-119774922,hs4:120692976-120692976;hs4:127297929-127297929,hs4:127807621-127807621;hs5:5047756-5047756,hs5:6852426-6852426;hs5:42469141-42469141,hs14:30281439-30281439;hs6:48357551-48357551,hs6:50749963-50749963;hs6:63616465-63616465,hs6:84434245-84434245;hs6:82603907-82603907,hs7:53341154-53341154;hs7:49054211-49054211,hs7:49953436-49953436;hs7:49054393-49054393,hs7:55818589-55818589;hs7:49060520-49060520,hs7:53194400-53194400;hs7:50412307-50412307,hs7:54178677-54178677;hs7:53075079-53075079,hs7:55070647-55070647;hs7:113323707-113323707,hs20:12562094-12562094;hs8:111397305-111397305,hs8:112322524-112322524;hs9:4933863-4933863,hs9:7116437-7116437;hs9:11792700-11792700,hs9:14442750-14442750;hs10:115681000-115681000,hs10:115845537-115845537;hs10:54455910-54455910,hs10:57145185-57145185;hs11:101644251-101644251,hs11:103267038-103267038;hs12:38001507-38001507,hs12:39769199-39769199;hs12:40262467-40262467,hs12:40831800-40831800;hs14:45355164-45355164,hs14:45493485-45493485;hs14:54079598-54079598,hs14:54846842-54846842;hs14:54916636-54916636,hs14:55538709-55538709;hs15:35224930-35224930,hs15:41296634-41296634;hs18:37589891-37589891,hs18:68238198-68238198;hsY:22665386-22665386,hsY:23228641-23228641 A1CF;AAA1;ABCA13;ABLIM1;ACO1;ADCY8;AFF2;AMPH;ANAPC1;ANKRD33B;ANXA2P2;AQR;ARFIP1;ARHGAP24;ARID1B;BCAR3;BRD8;BTBD3;C14orf182;C14orf28;C2orf88;C6orf35;C7orf10;C7orf58;C9orf150;C9orf46;C9orf93;CADM2;CAMK4;CASC2;CCDC102B;CCDC18;CCDC85A;CCDC92;CD226;CD274;CDC73;CDH2;CDK13;CDS1;CELF2;CELF4;CEP72;CHL1;CNBD1;CNKSR3;CNTN6;CNTNAP2;CNTNAP5;COL25A1;CPS1;CSMD3;CUL4A;CYB5R4;DACH2;DBX2;DDX10;DENND1A;DOK6;DOPEY2;DPP10;DPY19L1;DSCR4;DTNB;DYNC2H1;DYRK1A;EDIL3;EEPD1;EFHA2;EFNA5;ELMO1;EPHA5;EPHA6;EXOC3;EYS;FAM171B;FAM179B;FBXO8;FCGRT;FER;FIGNL1;FKBP9L;FLJ33360;FLJ35024;FNBP1L;FOXP2;FSTL5;GAD2;GALNT13;GALNTL6;GBE1;GCLM;GFM1;GFRA1;GHR;GLRA3;GPR141;GPR63;GRIA4;GRIN2B;HARS;HECW1;HERPUD2;HS3ST4;IBTK;IKZF1;IL15;IL33;INO80;INSL6;ITPR1;JAK2;KANK1;KCND2;KCNH8;KCNIP1;KCNJ6;KDM4C;KIAA0895;KIAA1328;KIAA1712;KIAA2026;KIF16B;KIF21A;KLHL29;KLRG1;LAMA3;LCORL;LOC100132891;LOC100302652;LOC150568;LOC285501;LOC340094;LPXN;MBP;MCC;MIR510;MLANA;MMP16;MTIF2;MTR;MYL1;NCAM1;NCRNA00182;NETO1;NFIB;NHSL2;NKAIN3;NKD2;NMD3;NRAP;NRG3;NTN4;NUDT21;ODZ2;OGFOD1;OPRM1;OSTN;PARK2;PCDH11Y;PDE6A;PGM5P2;PIGN;PIK3C2G;PIK3C3;PKD1L1;PKHD1;PLSCR5;PLXNC1;POT1;POU6F2;PRIM2;PRKD1;PRKG1;PRSS3;PTPRD;RB1;RBL2;RELL2;RFTN1;RFX3;RIC3;RIT2;ROBO1;RPRD2;RPS6KA2;RSPO3;RYR3;SAMD12;SCN9A;SEMA5A;SKA3;SLC1A1;SLC23A2;SLC2A13;SLC30A8;SLC39A12;SLCO3A1;SLITRK3;SND1;SORCS1;SPTLC3;STXBP6;SYNE1;SYT4;TASP1;TBC1D5;TBX18;TBX20;THSD7B;TMCO5A;TNIK;TNPO3;TNS3;TPR;TRDN;TRIM66;TRPM3;TSHZ1;TTC28;TTTY10;UBE2R2;UHRF2;USP28;VPS41;WDFY3;WDR17;ZBBX;ZDHHC14;ZFP161;ZNF407;ZNF804A; Harvard Medical School, Boston, MA 02115, USA The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term chromoplexy, frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. GRCh37/hg19 phs000447 Yes ABCA13,FIGNL1;ABLIM1,CASC2;AMPH,VPS41;AQR,INO80;ARID1B,ZDHHC14;BRD8,HARS;C9orf150,C9orf93;C9orf46,MLANA;C9orf46,PTPRD;CCDC18,GCLM;CDH2,TTC28;CDS1,ARHGAP24;CELF4,PIK3C3;CHL1,CNTN6;CNBD1,MMP16;CYB5R4,TBX18;DDX10,SKA3;DOK6,NETO1;DOPEY2,DYRK1A;DPY19L1,POU6F2;EEPD1,ELMO1;EEPD1,POU6F2;ELMO1,C7orf10;EXOC3,CEP72;EYS,ARID1B;EYS,SYNE1;FNBP1L,BCAR3;GHR,PRKD1;GLRA3,WDR17;GRIN2B,PIK3C2G;HECW1,ABCA13;HERPUD2,POU6F2;KCND2,SPTLC3;KCNJ6,DSCR4;KDM4C,PTPRD;KIAA0895,AMPH;KIAA0895,POU6F2;KIAA1328,RIT2;KIAA1712,GLRA3;MLANA,KDM4C;MYL1,CPS1;NCAM1,USP28;NHSL2,NCRNA00182;PLXNC1,NTN4;POU6F2,C7orf10;PRIM2,EYS;PRSS3,UBE2R2;PTPRD,NFIB;RFTN1,CADM2;RFX3,IL33;RFX3,INSL6;RIC3,TRIM66;RIT2,ZNF407;SLC23A2,SPTLC3;TBC1D5,CADM2;WDFY3,ARHGAP24 CTDB0278 Research 23622249 Baca SC, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, Van Allen E, Kryukov GV, Sboner A, Theurillat JP, Soong TD, Nickerson E, Auclair D, Tewari A, Beltran H, Onofrio RC, Boysen G, Guiducci C, Barbieri CE, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Ramos AH, Winckler W, Cipicchio M, Ardlie K, Kantoff PW, Berger MF, Gabriel SB, Golub TR, Meyerson M, Lander ES, Elemento O, Getz G, Demichelis F, Rubin MA, Garraway LA Punctuated evolution of prostate cancer genomes Cell 2013 Apr 1,2,3,4,5,6,7,8,10,11,12,13,18,X Prostate cancer Next Generation Sequencing Homo sapiens PR-3042 Illumina GAIIx chr10:0-25454692:0;chr10:110382241-110533895:-1;chr10:110533896-128896722:0;chr10:128896723-128901020:-1;chr10:128901021-134772725:0;chr10:134772726-134798521:-1;chr10:134798522-135534747:0;chr10:25454693-26134606:1;chr10:26134607-57123245:0;chr10:57123246-57153847:-1;chr10:57153848-58707392:0;chr10:58707393-58730327:-1;chr10:58730328-66878927:0;chr10:66878928-66929888:-1;chr10:66929889-110382240:0;chr11:0-91196261:0;chr11:106288702-106883908:-1;chr11:106883909-135006516:0;chr11:91196262-91217942:-1;chr11:91217943-106288701:0;chr12:0-22101860:0;chr12:127149458-127368094:-1;chr12:127368095-133851895:0;chr12:22101861-22107746:-1;chr12:22107747-61369674:0;chr12:61369675-61378699:-1;chr12:61378700-127149457:0;chr13:0-86949078:0;chr13:104423736-104805136:1;chr13:104805137-105211568:0;chr13:105211569-105410130:1;chr13:105410131-106904221:0;chr13:106904222-106906687:-1;chr13:106906688-115169878:0;chr13:86949079-86955460:-1;chr13:86955461-104423735:0;chr14:0-38047503:0;chr14:38047504-38408940:1;chr14:38408941-107349540:0;chr15:0-102531392:0;chr16:0-34448047:0;chr16:34448048-34467358:-1;chr16:34467359-90354753:0;chr17:0-81195210:0;chr18:0-25712896:0;chr18:25712897-25719640:-1;chr18:25719641-50415806:0;chr18:50415807-51315778:-1;chr18:51315779-61557581:0;chr18:61557582-61645698:-1;chr18:61645699-63069258:0;chr18:63069259-63089466:-1;chr18:63089467-65028428:0;chr18:65028429-65033616:-1;chr18:65033617-66422587:0;chr18:66422588-66441293:-1;chr18:66441294-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-139626096:0;chr2:139626097-139660580:-1;chr2:139660581-140356212:0;chr2:140356213-140362386:-1;chr2:140362387-141122718:0;chr2:141122719-141139084:-1;chr2:141139085-143912059:0;chr2:143912060-143921160:-1;chr2:143921161-163801167:0;chr2:163801168-163842011:-1;chr2:163842012-185203286:0;chr2:185203287-185206583:-1;chr2:185206584-185621785:0;chr2:185621786-185665148:-1;chr2:185665149-186929410:0;chr2:186929411-186939324:-1;chr2:186939325-196314961:0;chr2:196314962-196318364:-1;chr2:196318365-198719578:0;chr2:198719579-199633053:-1;chr2:199633054-221349035:0;chr2:221349036-221357571:-1;chr2:221357572-221894861:0;chr2:221894862-221896492:-1;chr2:221896493-243199373:0;chr3:0-53682501:0;chr3:116670867-117405142:-1;chr3:117190405-118116083:1;chr3:118116084-145670647:0;chr3:145670648-145682265:-1;chr3:145682266-146776104:0;chr3:146776105-147270982:-1;chr3:147270983-160274971:0;chr3:160274972-160893871:1;chr3:160421142-160912745:-1;chr3:160912746-162773503:0;chr3:162773504-162785085:-1;chr3:162785086-168698429:0;chr3:168698430-169220179:-1;chr3:168723458-169210633:1;chr3:168724386-169408170:-1;chr3:169408171-198022430:0;chr3:53682502-53684481:-1;chr3:53684482-75504717:0;chr3:75504718-75522878:-1;chr3:75522879-78361553:0;chr3:78361554-78990380:-1;chr3:78990381-95065081:0;chr3:95065082-95264557:1;chr3:95264558-116670866:0;chr4:0-46206781:0;chr4:100843081-100852463:-1;chr4:100852464-101079926:0;chr4:101079927-101090181:-1;chr4:101090182-113934948:0;chr4:113934949-114663708:-1;chr4:114663709-117754970:0;chr4:117754971-117760575:-1;chr4:117760576-137157838:0;chr4:137157839-137343754:-1;chr4:137343755-168528726:0;chr4:168528727-169318875:-1;chr4:169318876-170003985:0;chr4:170003986-170994628:1;chr4:170994629-171994712:0;chr4:171994713-171996934:-1;chr4:171996935-175726469:0;chr4:175726470-175728854:-1;chr4:175728855-187288939:0;chr4:187288940-187291308:-1;chr4:187291309-191154276:0;chr4:46206782-46213993:-1;chr4:46213994-46768843:0;chr4:46768844-46781686:-1;chr4:46781687-61637778:0;chr4:61637779-61639778:-1;chr4:61639779-63156116:0;chr4:63156117-63159632:-1;chr4:63159633-63645458:0;chr4:63645459-63664104:-1;chr4:63664105-64517775:0;chr4:64517776-64526606:-1;chr4:64526607-65391105:0;chr4:65391106-66300936:-1;chr4:66300937-67845919:0;chr4:67845920-68082508:-1;chr4:68082509-100843080:0;chr5:0-25807894:0;chr5:103114892-103153557:-1;chr5:103153558-104265669:0;chr5:104265670-104282304:-1;chr5:104282305-121789305:0;chr5:121789306-122484893:-1;chr5:122484894-127554609:0;chr5:127554610-127593216:-1;chr5:127593217-145937070:0;chr5:145937071-145951887:-1;chr5:145951888-158780222:0;chr5:158780223-158803186:-1;chr5:158803187-161440105:0;chr5:161440106-161446003:-1;chr5:161446004-178085328:0;chr5:178085329-178097441:-1;chr5:178097442-180915260:0;chr5:25807895-25820637:-1;chr5:25820638-91525113:0;chr5:91525114-91526254:-1;chr5:91526255-98137604:0;chr5:98137605-98308518:-1;chr5:98308519-103114891:0;chr6:0-85392925:0;chr6:85392926-85614671:-1;chr6:85614672-89079558:0;chr6:89079559-89104617:-1;chr6:89104618-171115067:0;chr7:0-57473577:0;chr7:57473578-57483160:-1;chr7:57483161-159138663:0;chr8:0-4126512:0;chr8:105493729-105499843:-1;chr8:105499844-127451031:0;chr8:127451032-127589423:1;chr8:127589424-146364022:0;chr8:4126513-4199023:-1;chr8:4199024-54319742:0;chr8:54319743-54649618:-1;chr8:54649619-55599018:0;chr8:55599019-56088347:-1;chr8:56088348-59529633:0;chr8:59529634-59542547:-1;chr8:59542548-65683657:0;chr8:65683658-66162090:1;chr8:66162091-73846961:0;chr8:73846962-73849486:-1;chr8:73849487-76160552:0;chr8:76160553-76166603:-1;chr8:76166604-78710497:0;chr8:78710498-78713895:-1;chr8:78713896-82272290:0;chr8:82272291-82278112:-1;chr8:82278113-84066903:0;chr8:84066904-84068544:-1;chr8:84068545-88134875:0;chr8:88134876-88141413:-1;chr8:88141414-88604324:0;chr8:88604325-88613225:-1;chr8:88613226-105493728:0;chr9:0-26666039:0;chr9:26666040-26670489:-1;chr9:26670490-141213431:0;chrX:0-25869599:0;chrX:142657250-142661549:-1;chrX:142661550-145090901:0;chrX:145090902-145105563:-1;chrX:145105564-155270560:0;chrX:25869600-26266151:-1;chrX:26266152-65314921:0;chrX:65314922-65320368:-1;chrX:65320369-90080139:0;chrX:90080140-91006527:-1;chrX:91006528-92504931:0;chrX:92504932-92505894:-1;chrX:92505895-142657249:0;chrY:0-59373566:0 hs3:115803858-115803858,hs3:119782994-119782994;hs8:65380698-65380698,hs8:67243448-67243448;hs8:55231731-55231731,hs8:65253509-65253509;hs8:54325675-54325675,hs8:57739326-57739326;hs8:56250627-56250627,hs8:62222354-62222354;hs8:64600820-64600820,hs8:66798087-66798087;hs8:53932943-53932943,hs8:57216646-57216646;hs8:56425962-56425962,hs8:62269658-62269658;hs13:41261914-41261914,hs13:104375292-104375292;hs4:171617153-171617153,hs4:173054022-173054022;hs8:54329084-54329084,hs8:56384037-56384037;hs8:55838961-55838961,hs8:62361313-62361313;hs8:31493507-31493507,hs8:79566762-79566762;hs8:59530449-59530449,hs8:61284178-61284178;hs8:63760036-63760036,hs8:63765351-63765351;hs8:84338979-84338979,hs8:84907102-84907102;hs8:75867853-75867853,hs11:134660389-134660389;hs8:91453364-91453364,hs11:132545826-132545826;hsX:33312499-33312499,hsX:82311507-82311507;hs3:103473443-103473443,hs3:163725208-163725208;hs8:55268641-55268641,hs8:61227247-61227247;hs8:56385004-56385004,hs8:65669009-65669009;hs8:57767446-57767446,hs8:59533685-59533685;hs8:54330275-54330275,hs8:67326858-67326858;hs8:56561747-56561747,hs8:65336224-65336224;hs8:86109269-86109269,hs11:123887876-123887876;hs3:103934508-103934508,hs3:115020345-115020345;hs4:30745170-30745170,hs4:35239709-35239709;hs5:106198977-106198977,hs5:129545320-129545320;hs6:66896854-66896854,hs6:122612911-122612911;hs6:124582381-124582381,hs6:129613851-129613851;hs8:55429253-55429253,hs8:56777668-56777668;hs8:64297363-64297363,hs8:66699413-66699413;hs8:64330250-64330250,hs8:65060111-65060111;hs8:65949673-65949673,hs8:67040332-67040332;hs8:56148696-56148696,hs8:63699937-63699937;hs8:84870817-84870817,hs11:124347074-124347074;hs8:80393603-80393603,hs11:104506231-104506231;hs2:49418442-49418442,hs2:51368692-51368692;hs3:94610925-94610925,hs3:94978611-94978611;hs3:160094726-160094726,hs3:161776532-161776532;hs8:13962427-13962427,hs8:79502475-79502475;hs8:53934185-53934185,hs8:56382646-56382646;hs8:57740356-57740356,hs8:59850518-59850518;hs3:76739651-76739651,hs3:147265508-147265508;hs3:79648937-79648937,hs6:122826643-122826643;hs3:77493657-77493657,hs11:38461255-38461255;hs4:63525336-63525336,hs4:67816538-67816538;hs4:66230265-66230265,hs4:118124501-118124501;hs10:25390567-25390567,hs10:50673223-50673223;hs1:217134531-217134531,hs1:238169411-238169411;hs2:51364316-51364316,hs2:51594415-51594415;hs3:159369077-159369077,hs3:159628554-159628554;hs3:116662259-116662259,hs3:166808301-166808301;hs3:156928365-156928365,hs6:123201920-123201920;hs4:58688184-58688184,hs5:24474191-24474191;hs8:54629264-54629264,hs8:57396320-57396320;hs8:55805279-55805279,hs8:64224739-64224739;hs8:57739541-57739541,hs8:65963971-65963971;hs8:83667886-83667886,hs11:133060044-133060044;hs12:17746531-17746531,hs12:23999608-23999608;hs12:18310290-18310290,hs12:25545464-25545464;hsX:112026227-112026227,hsX:118319308-118319308;hs1:86862038-86862038,hs1:88171079-88171079;hs3:115871821-115871821,hs3:117917555-117917555;hs3:120748096-120748096,hs3:165361905-165361905;hs3:146745762-146745762,hs6:128950759-128950759;hs3:147293494-147293494,hs11:48106303-48106303;hs4:35047957-35047957,hs4:38470529-38470529;hs4:137328555-137328555,hs4:169884708-169884708;hs4:36741171-36741171,hs10:116803835-116803835;hs5:99541527-99541527,hs5:110334271-110334271;hs5:101209011-101209011,hs5:111500413-111500413;hs5:142616670-142616670,hs5:168735722-168735722;hs8:75238415-75238415,hs8:84397806-84397806;hs10:113771062-113771062,hs10:121042883-121042883;hs12:21818298-21818298,hs12:25443171-25443171;hsX:23827578-23827578,hsX:24657376-24657376;hsX:78667487-78667487,hsX:81074947-81074947;hs2:137665267-137665267,hs2:141177469-141177469;hs2:198737472-198737472,hs2:198800457-198800457;hs3:76351234-76351234,hs3:76355474-76355474;hs3:78107089-78107089,hs3:150737540-150737540;hs3:95589588-95589588,hs3:164203073-164203073;hs3:103225362-103225362,hs3:161937421-161937421;hs3:115760367-115760367,hs3:117221413-117221413;hs3:160248272-160248272,hs3:163726170-163726170;hs3:317943-317943,hs4:183508345-183508345;hs4:64533781-64533781,hs4:65651175-65651175;hs4:165578484-165578484,hs5:152247797-152247797;hs5:23191107-23191107,hs5:44548798-44548798;hs5:80772858-80772858,hs5:106473001-106473001;hs5:98925684-98925684,hs5:109703134-109703134;hs12:127350660-127350660,hs12:130166612-130166612;hs13:40310828-40310828,hs13:41368329-41368329;hs13:56820406-56820406,hs13:105381250-105381250;hs13:57010346-57010346,hs13:105970124-105970124;hsX:109621525-109621525,hsX:112031984-112031984;hs3:75828994-75828994,hs3:78093335-78093335;hs3:116667407-116667407,hs3:118082242-118082242;hs3:155161652-155161652,hs6:126926037-126926037;hs3:79839964-79839964,hs6:123247909-123247909;hs3:77038594-77038594,hs11:38440992-38440992;hs4:64532563-64532563,hs4:65652201-65652201;hs4:58301048-58301048,hs5:45757532-45757532;hs5:76763194-76763194,hs5:78112821-78112821;hs5:101125118-101125118,hs5:102842612-102842612;hs5:75343880-75343880,hs5:92739200-92739200;hs6:64306312-64306312,hs6:129622557-129622557;hs7:32592689-32592689,hs7:50671491-50671491;hs7:32144140-32144140,hs7:49924196-49924196;hs8:90142065-90142065,hs11:132525788-132525788;hs10:38639681-38639681,hs10:66405881-66405881;hs11:87887096-87887096,hs11:89889147-89889147;hs13:41522909-41522909,hs13:81337746-81337746;hs13:40359952-40359952,hs13:103955106-103955106;hs13:41767353-41767353,hs13:57249916-57249916;hsX:82330908-82330908,hsX:143885300-143885300;hsX:109623198-109623198,hsX:118307576-118307576;hsX:92514146-92514146,hsX:142422552-142422552;hs2:118631594-118631594,hs2:132794589-132794589;hs3:75271564-75271564,hs3:147302004-147302004;hs3:77124475-77124475,hs3:154249388-154249388;hs3:94433783-94433783,hs3:95643181-95643181;hs3:99491667-99491667,hs3:100112505-100112505;hs3:116677073-116677073,hs3:166807481-166807481;hs3:145667700-145667700,hs3:149295667-149295667;hs3:159581244-159581244,hs3:161194569-161194569;hs3:161770275-161770275,hs3:164661415-164661415;hs3:115859818-115859818,hs3:165689976-165689976;hs3:79315718-79315718,hs6:124561730-124561730;hs3:146441954-146441954,hs6:64354732-64354732;hs3:156887171-156887171,hs6:64769220-64769220;hs3:79620754-79620754,hs11:36958610-36958610;hs3:79632011-79632011,hs11:37495497-37495497;hs4:112897314-112897314,hs4:126787639-126787639;hs4:137168066-137168066,hs4:171010043-171010043;hs4:170976540-170976540,hs4:171075668-171075668;hs4:64531201-64531201,hs4:66302181-66302181;hs4:58690825-58690825,hs5:24788834-24788834;hs4:59477478-59477478,hs5:24504304-24504304;hs4:112795042-112795042,hs5:126672193-126672193;hs4:146192392-146192392,hs5:103768510-103768510;hs4:137452747-137452747,hs10:110001123-110001123;hs5:27090897-27090897,hs5:31108074-31108074;hs5:107708686-107708686,hs5:110489050-110489050;hs10:67103425-67103425,hs10:83034305-83034305;hs11:90042361-90042361,hs11:91073888-91073888;hs12:17668815-17668815,hs12:23925210-23925210;hs12:17670314-17670314,hs12:24232952-24232952;hsX:77878072-77878072,hsX:114810694-114810694;hsX:82275059-82275059,hsX:146629017-146629017;hsX:63953324-63953324,hsX:78616169-78616169;hs3:100320756-100320756,hs3:163924279-163924279;hs3:103428939-103428939,hs3:160604128-160604128;hs3:103785751-103785751,hs3:165314814-165314814;hs3:114978385-114978385,hs3:120818118-120818118;hs3:116454570-116454570,hs3:165782625-165782625;hs3:117912837-117912837,hs3:120595790-120595790;hs3:120149825-120149825,hs3:168414662-168414662;hs3:120022120-120022120,hs3:167252817-167252817;hs3:100321832-100321832,hs3:161260185-161260185;hs3:161936593-161936593,hs3:164149929-164149929;hs3:75502060-75502060,hs17:22189653-22189653;hs4:169307282-169307282,hs4:173945797-173945797;hs4:58292579-58292579,hs5:24001175-24001175;hs5:91498786-91498786,hs5:112638923-112638923;hs6:96511917-96511917,hs6:115933194-115933194;hs6:124821086-124821086,hs6:126790196-126790196;hs7:48922675-48922675,hs7:50673984-50673984;hs8:76672871-76672871,hs8:78430765-78430765;hs11:124374093-124374093,hs11:133088045-133088045;hs12:17391666-17391666,hs12:25523150-25523150;hs12:25445764-25445764,hs12:26935455-26935455;hs13:81335892-81335892,hs13:82469631-82469631;hs13:40795848-40795848,hs13:106173013-106173013;hs13:81366207-81366207,hs13:103958693-103958693;hsX:30954054-30954054,hsX:88383742-88383742;hs1:73615241-73615241,hs1:238602682-238602682;hs3:162282705-162282705,hs3:163359115-163359115;hs3:95093371-95093371,hs4:183518348-183518348;hs3:120122865-120122865,hs4:144661396-144661396;hs3:80404752-80404752,hs6:123549472-123549472;hs3:155532127-155532127,hs11:48465721-48465721;hs4:59477306-59477306,hs4:59487565-59487565;hs4:64576114-64576114,hs4:158485572-158485572;hs4:109948755-109948755,hs4:111690650-111690650;hs4:117710986-117710986,hs4:158458850-158458850;hs4:170973072-170973072,hs4:173056766-173056766;hs4:171074705-171074705,hs4:173950007-173950007;hs4:65652169-65652169,hs4:117614336-117614336;hs4:30728523-30728523,hs10:116764749-116764749;hs4:126757501-126757501,hs10:110411808-110411808;hs4:130498679-130498679,hs10:110765885-110765885;hs5:75322739-75322739,hs5:94641006-94641006;hs5:77456412-77456412,hs5:99234361-99234361;hs5:101429229-101429229,hs5:153130535-153130535;hs5:108863344-108863344,hs5:161387086-161387086;hs5:162733564-162733564,hs5:167531194-167531194;hs5:122488154-122488154,hs5:126588445-126588445;hs8:54665372-54665372,hs8:61332068-61332068;hs8:56162877-56162877,hs8:56486496-56486496;hs8:90493075-90493075,hs8:90841680-90841680;hs8:89183893-89183893,hs8:91316323-91316323;hs10:83024810-83024810,hs10:113605502-113605502;hs11:89999390-89999390,hs11:90488837-90488837;hs12:21432374-21432374,hs12:45375328-45375328;hs13:81702392-81702392,hs13:82319483-82319483;hsX:114794541-114794541,hsX:118317638-118317638;hs1:86861781-86861781,hs1:88171064-88171064;hs2:132518282-132518282,hs2:163142818-163142818;hs2:140387040-140387040,hs11:105869444-105869444;hs3:99542247-99542247,hs3:160437164-160437164;hs3:160142460-160142460,hs3:163288378-163288378;hs3:161251297-161251297,hs3:163899170-163899170;hs3:77482151-77482151,hs3:145644364-145644364;hs3:159937750-159937750,hs3:161235937-161235937;hs3:159965863-159965863,hs3:164110305-164110305;hs3:159338257-159338257,hs3:159778895-159778895;hs3:146817931-146817931,hs6:125915261-125915261;hs3:150322674-150322674,hs6:125091054-125091054;hs3:80266360-80266360,hs6:64532240-64532240;hs4:35249463-35249463,hs4:36870795-36870795;hs4:131959500-131959500,hs4:133716722-133716722;hs4:165573687-165573687,hs5:104452349-104452349;hs5:24480506-24480506,hs5:45356826-45356826;hs5:81712028-81712028,hs5:104677744-104677744;hs5:106401204-106401204,hs5:109395266-109395266;hs5:109394595-109394595,hs5:110583120-110583120;hs5:122491415-122491415,hs5:162514743-162514743;hs5:97571860-97571860,hs5:106402878-106402878;hs5:92747939-92747939,hs5:107918164-107918164;hs5:107407890-107407890,hs10:133073821-133073821;hs7:49699154-49699154,hs7:49949354-49949354;hs8:34061467-34061467,hs8:50099460-50099460;hs8:90508815-90508815,hs8:91494393-91494393;hs8:80676526-80676526,hs11:126853630-126853630;hs10:25305875-25305875,hs10:83015119-83015119;hs11:102415906-102415906,hs11:105907697-105907697;hs12:18341439-18341439,hs12:21443679-21443679;hsX:77991776-77991776,hsX:79474465-79474465;hsX:79445709-79445709,hsX:108846627-108846627;hs2:199629281-199629281,hs2:210103065-210103065;hs3:159800292-159800292,hs3:163328310-163328310;hs3:120528986-120528986,hs3:120540104-120540104;hs3:95074505-95074505,hs4:182252327-182252327;hs4:59585011-59585011,hs4:110764648-110764648;hs4:63355932-63355932,hs4:118185646-118185646;hs4:110529968-110529968,hs4:111697024-111697024;hs4:122342536-122342536,hs4:123426512-123426512;hs4:122765374-122765374,hs4:130692599-130692599;hs4:146186942-146186942,hs5:103777486-103777486;hs5:26860464-26860464,hs5:28681961-28681961;hs5:31010166-31010166,hs5:31251056-31251056;hs5:100367418-100367418,hs5:102802614-102802614;hs5:122489382-122489382,hs5:126611614-126611614;hs5:161393780-161393780,hs5:162514839-162514839;hs5:100986145-100986145,hs5:153046655-153046655;hs6:123038740-123038740,hs11:36960359-36960359;hs8:34027530-34027530,hs8:50099023-50099023;hs8:54329104-54329104,hs8:66812848-66812848;hs8:58244654-58244654,hs11:124106190-124106190;hs10:66958337-66958337,hs10:83061923-83061923;hs11:87634861-87634861,hs11:88081155-88081155;hs11:102413719-102413719,hs11:104328373-104328373;hs12:17562977-17562977,hs12:26435098-26435098;hs12:17568744-17568744,hs12:24231983-24231983;hs12:127167496-127167496,hs12:130203064-130203064;hs13:81885912-81885912,hs13:104445546-104445546;hs13:104973515-104973515,hs13:105768778-105768778;hsX:28574488-28574488,hsX:144175133-144175133;hs2:138345512-138345512,hs2:141186625-141186625;hs3:116717493-116717493,hs3:117751015-117751015;hs3:120047316-120047316,hs3:169385363-169385363;hs3:120224480-120224480,hs3:167192189-167192189;hs3:146781469-146781469,hs3:154257559-154257559;hs3:146919152-146919152,hs3:150739999-150739999;hs3:364144-364144,hs4:180354462-180354462;hs3:120124300-120124300,hs4:144656174-144656174;hs4:109957244-109957244,hs4:111412698-111412698;hs4:113076841-113076841,hs4:125249736-125249736;hs4:133838159-133838159,hs4:135580477-135580477;hs4:137429794-137429794,hs10:110018850-110018850;hs5:24005647-24005647,hs5:45836553-45836553;hs5:31089305-31089305,hs5:31231890-31231890;hs5:78737041-78737041,hs5:110301706-110301706;hs5:128032505-128032505,hs10:130165930-130165930;hs8:89981913-89981913,hs8:90700892-90700892;hs8:84921305-84921305,hs11:124810627-124810627;hs10:25389699-25389699,hs10:50656655-50656655;hs11:50169328-50169328,hs11:50542211-50542211;hs13:40987763-40987763,hs13:82500216-82500216;hs13:57003180-57003180,hs13:105950784-105950784;hsX:92524917-92524917,hsX:142424948-142424948;hs3:94635301-94635301,hs3:95273220-95273220;hs3:160590744-160590744,hs3:162311059-162311059;hs3:161402344-161402344,hs3:162603146-162603146;hs3:163342135-163342135,hs3:164698827-164698827;hs4:112469857-112469857,hs10:130889783-130889783;hs5:76832359-76832359,hs5:107620499-107620499;hs5:104451172-104451172,hs5:152251593-152251593;hs5:157293154-157293154,hs5:160205336-160205336;hs5:106183041-106183041,hs10:133249138-133249138;hs7:31741789-31741789,hs7:48876007-48876007;hs7:32565822-32565822,hs7:49671241-49671241;hs8:86128006-86128006,hs11:123872374-123872374;hs10:27170073-27170073,hs10:66333655-66333655;hs12:16934737-16934737,hs12:38714903-38714903;hs12:38645015-38645015,hs12:38715641-38715641;hs16:50879237-50879237,hs16:85963558-85963558;hsX:28576942-28576942,hsX:144198068-144198068;hs2:157085050-157085050,hs2:167502737-167502737;hs2:198789157-198789157,hs2:199944999-199944999;hs3:77123280-77123280,hs3:78524644-78524644;hs3:102983709-102983709,hs3:162787566-162787566;hs3:120032266-120032266,hs3:167314584-167314584;hs3:120529003-120529003,hs3:120748275-120748275;hs3:168413056-168413056,hs3:168416564-168416564;hs3:77053503-77053503,hs11:48090479-48090479;hs4:112588203-112588203,hs4:129833482-129833482;hs4:113093651-113093651,hs4:123407192-123407192;hs4:122492103-122492103,hs4:123616212-123616212;hs4:122778330-122778330,hs4:136428713-136428713;hs4:123613565-123613565,hs4:127953355-127953355;hs4:124624780-124624780,hs4:126973711-126973711;hs4:60165596-60165596,hs4:111511942-111511942;hs4:129836465-129836465,hs5:21934544-21934544;hs5:126636684-126636684,hs10:130560347-130560347;hs5:128727950-128727950,hs10:130210596-130210596;hs10:128821547-128821547,hs10:130550145-130550145;hs11:104509186-104509186,hs11:126888779-126888779;hs2:200101344-200101344,hs2:209181236-209181236;hs2:140416895-140416895,hs11:104337243-104337243;hs3:76351051-76351051,hs3:76354886-76354886;hs3:103928902-103928902,hs3:120768924-120768924;hs4:36323105-36323105,hs4:38520509-38520509;hs4:110832312-110832312,hs4:124252278-124252278;hs4:112543323-112543323,hs4:128338844-128338844;hs4:114806564-114806564,hs4:126985180-126985180;hs4:126993532-126993532,hs4:135932856-135932856;hs4:127935573-127935573,hs4:127995480-127995480;hs4:110550370-110550370,hs5:46343229-46343229;hs4:110844245-110844245,hs5:21959442-21959442;hs4:111192634-111192634,hs10:134438072-134438072;hs5:143103546-143103546,hs5:169678124-169678124;hs5:129550165-129550165,hs10:134422454-134422454;hs6:123545009-123545009,hs6:128325325-128325325;hsX:108850811-108850811,hsX:118305350-118305350;hs4:114769182-114769182,hs4:122467758-122467758;hs4:121439341-121439341,hs4:126967346-126967346;hs4:124284303-124284303,hs4:124624248-124624248;hs4:128368405-128368405,hs4:136420975-136420975;hs4:121410629-121410629,hs4:122340189-122340189;hs4:36349471-36349471,hs10:113778516-113778516;hs4:135946319-135946319,hs10:110533797-110533797;hs5:157292642-157292642,hs5:160188651-160188651;hs8:80723051-80723051,hs8:80920235-80920235;hs13:105109913-105109913,hs13:105247498-105247498;hs13:105964061-105964061,hs13:106071882-106071882;hs13:96689784-96689784,hs14:83833625-83833625;hs13:96285985-96285985,hs21:44524274-44524274;hsX:62571634-62571634,hsX:84183647-84183647;hs1:222748063-222748063,hs2:203617057-203617057;hs2:17880963-17880963,hs7:73379503-73379503;hs3:120124044-120124044,hs3:168724380-168724380;hs4:112979945-112979945,hs4:126965471-126965471;hs4:112911938-112911938,hs10:111299781-111299781;hs4:170515243-170515243,hs20:54970301-54970301;hs5:142616714-142616714,hs5:168745745-168745745;hs6:123256601-123256601,hs11:37552474-37552474;hs12:21842642-21842642,hs12:23991197-23991197;hs14:98423572-98423572,hs17:64654974-64654974;hs15:98000467-98000467,hs18:12346965-12346965;hs18:27242096-27242096,hs18:27248915-27248915;hs1:248749448-248749448,hs7:133712447-133712447;hs2:220667388-220667388,hs3:26133874-26133874;hs2:5920102-5920102,hs7:100040509-100040509;hs2:64200385-64200385,hs8:141445171-141445171;hs3:46767017-46767017,hs5:32034442-32034442;hs4:30864023-30864023,hs4:32773056-32773056;hs4:21423750-21423750,hs5:24663502-24663502;hs4:162782343-162782343,hs7:6699870-6699870;hs4:89167105-89167105,hs8:82680320-82680320;hs5:79926480-79926480,hs5:161964981-161964981;hs5:75803881-75803881,hs19:34769615-34769615;hs5:86439553-86439553,hsX:51381386-51381386;hs6:164969640-164969640,hs7:142025397-142025397;hs6:33102865-33102865,hs11:4613692-4613692;hs6:160840732-160840732,hs12:32731886-32731886;hs6:104195978-104195978,hs15:51206950-51206950;hs7:68199039-68199039,hs13:45690872-45690872;hs8:133506091-133506091,hs11:133085495-133085495;hs8:113362608-113362608,hs15:95714904-95714904;hs10:128799277-128799277,hs10:133179776-133179776;hs10:82540444-82540444,hs14:89092876-89092876;hs10:44292335-44292335,hs16:57369910-57369910;hs10:119986618-119986618,hsX:35728541-35728541;hs12:73579822-73579822,hs17:17493733-17493733;hs22:38015725-38015725,hs22:42157226-42157226 AADAT;AFG3L2;ALG10B;AMMECR1;AMOT;ANK2;AP3B1;AP4E1;ARHGAP15;ARSB;ATP10B;ATP6V1H;AVL9;BBS7;C14orf64;C2orf27A;C3orf26;C4orf32;C7orf16;C8orf59;CACNA1D;CAMK2D;CAMK4;CCDC102B;CCDC109B;CDH10;CDH12;CDH2;CDH6;CHL1;CLRN1OS;CLVS1;CNBD1;COG6;COL25A1;COX7B2;CSMD1;CSMD3;CSTF1;CYP7B1;DCC;DDX60L;DHFR;DMD;DNAJB14;DOCK1;DTHD1;DZIP1;E2F5;EGF;ELF1;EML5;ENPEP;EPB41L4A;EPHA5;ERCC6;ESRRG;EXOC4;EYS;FAM117B;FBXL17;FGD4;FLJ42709;FSTL1;FSTL5;FUT9;GALNTL6;GGA1;GLRA3;GRB10;GRIA1;GRK5;GSK3B;GUCY1A2;HCN1;HEY1;HOMER1;IFIH1;IFT80;INPP5A;IQGAP2;ITM2A;ITPR2;KBTBD7;KCNB2;KIAA0355;KIRREL3;KPNA4;LAMA2;LCP2;LOC100128811;LOC285419;LOC646982;LRP1B;LRRC58;LSAMP;MCC;MECOM;MEGF10;MEI1;MIR548A3;MIR548G;MMP16;MRPS28;NAALAD2;NCRNA00259;NEK1;NKAIN2;NKAIN3;NSMAF;ODF2L;ODZ2;ODZ3;OPCML;OR52I1;PCDH7;PCYT1B;PDE7A;PDZD2;PEMT;PHF3;PIKFYVE;PKIA;PKIB;PLCL1;PLS3;PPM1L;PRDM6;PRKCA;PTPRJ;RAB38;ROBO1;ROBO2;RRH;SCHIP1;SCLT1;SDR16C5;SELT;SERPINB2;SERPINB8;SERPINI2;SGCZ;SI;SLC22A3;SLC25A15;SLCO1A2;SMC4;SMC6;SNCAIP;SOX5;SPIN4;SSBP2;STXBP5L;TAF1A;TCERG1L;THNSL1;THSD7B;TMEM132D;TOMM70A;TOX;TRAPPC9;TRDN;TRIM55;U2AF1;UGGT2;VPS54;VWC2;WDR41;WDR49;WWTR1;XKR4;ZNF717;ZNF804A; Harvard Medical School, Boston, MA 02115, USA The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term chromoplexy, frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. GRCh37/hg19 phs000447 Yes TAF1A,FAM117B;C2orf27A,IFIH1;THSD7B,LRP1B;VPS54,TRAPPC9;LSAMP,GSK3B;ROBO1,PKIB;CHL1,ODZ3;MIR548G,TOMM70A;ROBO1,NKAIN2;FSTL1,NCRNA00259;SELT,NKAIN2;MIR548A3,STXBP5L;DDX60L,GALNTL6;ANK2,CAMK2D;COL25A1,ENPEP;SCLT1,CDH12;EGF,CDH12;NEK1,CSTF1;WDR41,ARSB;FBXL17,TCERG1L;SNCAIP,PRDM6;IQGAP2,KIAA0355;NKAIN2,LAMA2;TRDN,PTPRK;SLC22A3,FGD4;AVL9,GRB10;XKR4,CLVS1;XKR4,CLVS1;XKR4,CYP7B1;XKR4,NKAIN3;SGCZ,PKIA;HEY1,KIRREL3;RAB38,NAALAD2;COG6,SLC25A15;DZIP1,U2AF1;SERPINB2,SERPINB8;AMMECR1,AMOT CTDB0279 Methodology 23940299 Sanborn JZ, Salama SR, Grifford M, Brennan CW, Mikkelsen T, Jhanwar S, Katzman S, Chin L, Haussler D Double minute chromosomes in glioblastoma multiforme are revealed by precise reconstruction of oncogenic amplicons Cancer Research 2013 Oct 9,12 Glioblastoma Next Generation Sequencing Homo sapiens TCGA-06-0648 chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-65837944:0;chr12:65837945-66055069:1;chr12:66055070-66055380:0;chr12:66055381-66072676:1;chr12:66072677-66075067:0;chr12:66075068-66100528:1;chr12:66100529-66344990:0;chr12:66344991-66358803:1;chr12:66358804-66359378:0;chr12:66359379-66448933:1;chr12:66448934-66681859:0;chr12:66681860-66764263:1;chr12:66764264-67035467:0;chr12:67035468-67050196:1;chr12:67050197-67051074:0;chr12:67051075-67085451:1;chr12:67085452-67316332:0;chr12:67316333-67368167:1;chr12:67368168-67451017:0;chr12:67451018-67459422:1;chr12:67459423-67472942:0;chr12:67472943-67530895:1;chr12:67530896-67531675:0;chr12:67531676-67537257:1;chr12:67537177-67628514:1;chr12:67628515-67770598:0;chr12:67770599-67890243:1;chr12:67890244-67960817:0;chr12:67960818-68022264:1;chr12:68022265-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-146364022:0;chr9:0-135834391:0;chr9:135834392-135834618:1;chr9:135834619-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs12:66358555-66358803,hs12:66763926-66764263;hs12:67810680-67810853,hsX:54320719-54320744;hs12:66350731-66350875,hsX:101299719-101299730;hs12:66650577-66650728,hs12:68023553-68023715;hs12:67053755-67053878,hs3:185454999-185455012;hs12:66054835-66055069,hs9:135834530-135834618;hs12:67363426-67363508,hs12:67528856-67528980;hs12:66687266-66687380,hs12:67533819-67533978;hs12:66398631-66398792,hs13:99673601-99673672;hs12:66074586-66074631,hs12:66681079-66681202;hs12:65957502-65957622,hs22:48775252-48775370;hs12:66055381-66055730,hs12:67537177-67537541;hs12:66344991-66345249,hs12:68021986-68022264;hs12:66054950-66055111,hs12:67472904-67473224;hs12:66733983-66734166,hs12:67580167-67580368;hs12:67051075-67051320,hs12:67451018-67451391;hs12:65837945-65838144,hs12:66448613-66448929;hs12:67815282-67815471,hs5:136666111-136666114;hs12:67527252-67527522,hs8:97167579-97167625;hs12:66748792-66748921,hs22:48937381-48937494;hs12:66100207-66100528,hs12:66681860-66682114;hs12:66420984-66421144,hs22:48835485-48835755;hs12:65929775-65929897,hs16:72726677-72726693;hs12:66073329-66073520,hs12:68065659-68065870;hs12:65896905-65897114,hs22:48637321-48637414;hs12:67073429-67073694,hs2:210642752-210642758;hs12:65839551-65839775,hs12:67825318-67825523;hs12:66075068-66075262,hs12:66359379-66359603;hs12:66700571-66700720,hs12:67072869-67072995;hs12:67530575-67530895,hs12:67770599-67770946;hs12:66072398-66072676,hs12:67889923-67890243;hs12:67085146-67085451,hs12:67536855-67537257;hs12:66050493-66050661,hs12:67577290-67577451;hs12:67531676-67531994,hs12:67628278-67628514;hs12:65887474-65887619,hs12:66694681-66694764;hs12:67818920-67819049,hs12:67980392-67980597;hs12:66732589-66732838,hs12:67580851-67581048;hs12:65837358-65837535,hs12:66164005-66164163;hs12:67367906-67368167,hs12:67960818-67961176;hs12:66687038-66687251,hs12:66754719-66754944;hs12:66683943-66684150,hs12:67805028-67805235;hs12:66755375-66755599,hs22:48635052-48635262;hs12:66025353-66025516,hs12:67554147-67554310;hs12:66016636-66016807,hs12:67058039-67058166;hs12:77803075-77803262,hs12:77803962-77804154;hs12:66243020-66243174,hs12:68065211-68065389;hs12:67049932-67050196,hs12:67316333-67316622;hs12:67515167-67515368,hs22:48690695-48690822;hs12:67321187-67321363,hs12:67843584-67843723;hs12:66400478-66400626,hs12:66412238-66412335;hs12:67035468-67035754,hs12:67459177-67459422;hs12:67074005-67074173,hs12:67844346-67844539;hs12:67472943-67473166,hs9:135834392-135834455;hs12:66401802-66401926,hs22:48848404-48848491;hs11:79450674-79450830,hs11:80247904-80248042;hs11:79425728-79425819,hs11:79447098-79447288;hs10:41728216-41728245,hs12:34745551-34745589;hs10:89516908-89517093,hs10:90653020-90653202;hs17:38912647-38912708,hs18:22227376-22227382;hs17:53013168-53013311,hs9:133612391-133612402;hs16:33857992-33859041,hsY:10627235-10628113;hs16:44958667-44959283,hs16:44960910-44961126;hs18:23217516-23217616,hs18:23218933-23219067;hs18:9228780-9228918,hs18:28596414-28596522;hs18:6736317-6736424,hs18:9345292-9345390;hs18:23989851-23990016,hs18:25650633-25650732;hs22:43109344-43109475,hs22:47708183-47708278;hs22:16885769-16885970,hs22:27523748-27523905;hs22:32763567-32763679,hs22:34393075-34393220;hs22:48678833-48678909,hs22:48852675-48852853;hs22:22015300-22015539,hs22:47777107-47777218;hs22:48673340-48673445,hs22:48722186-48722353;hs22:24929222-24929428,hs22:40784068-40784160;hs21:9720926-9720996,hs22:31454215-31454364;hs4:19998865-19999046,hs4:23433162-23433339;hs4:20191878-20192072,hs4:24068204-24068405;hs4:132809659-132809830,hs9:46294195-46294249;hs4:23137392-23137577,hs4:23888373-23888532;hs3:189740345-189740559,hs3:189876644-189876856;hs3:189738944-189739176,hs3:189742505-189742694;hs2:34557918-34557933,hs8:1416822-1416965;hs2:90966487-90967031,hs2:90977116-90978255;hs2:132762009-132762204,hs4:49210357-49210657;hs9:26048012-26048215,hs9:26536336-26536547;hs9:26539731-26539905,hs9:26732158-26732349;hs9:21475882-21476028,hs9:24304363-24304486;hs9:22220584-22220728,hs9:26095687-26095879;hs9:22507025-22507200,hs9:23373840-23374045;hs9:22452340-22452487,hs9:26944351-26944522;hs9:26694112-26694315,hs9:27403094-27403295;hs9:26695268-26695371,hs9:26949108-26949215;hs9:21383845-21383945,hs9:22047421-22047481;hs9:23562681-23562871,hs9:25540621-25540790;hs9:25539461-25539653,hs9:26725709-26725925;hs9:25461325-25461478,hs9:26047803-26047970;hs9:23648745-23648896,hs9:26108310-26108481;hs9:22601786-22601913,hs9:27291204-27291405 AK127888;ALG10;ALG10B;ANKRD20A2;BC022082;C4orf33;C8orf37;C9orf11;C9orf82;CAND1;CDKN2B;CPM;CPSF6;DMRTA1;DQ575272;DYRK2;ELAVL2;FAM75A7;GRIP1;IFNA2;IFNA8;IFNE;IFNG;IFT74;LYZ;MDM1;MDM2;MED27;MGC50273;MOBKL2B;MTAP;NAV3;NUP107;PLAA;RAP1B;RAPGEF1;SLC35E3;SYT1;tmp_locus_39;TUSC1;VAV2;YEATS4; Five3 Genomics, LLC, Santa Cruz, CA, 9506 DNA sequencing offers a powerful tool in oncology based on the precise definition of structural rearrangements and copy number in tumor genomes. Here, we describe the development of methods to compute copy number and detect structural variants to locally reconstruct highly rearranged regions of the tumor genome with high precision from standard, short-read, paired-end sequencing datasets. We find that circular assemblies are the most parsimonious explanation for a set of highly amplified tumor regions in a subset of glioblastoma multiforme samples sequenced by The Cancer Genome Atlas (TCGA) consortium, revealing evidence for double minute chromosomes in these tumors. Further, we find that some samples harbor multiple circular amplicons and, in some cases, further rearrangements occurred after the initial amplicon-generating event. Fluorescence in situ hybridization analysis offered an initial confirmation of the presence of double minute chromosomes. Gene content in these assemblies helps identify likely driver oncogenes for these amplicons. RNA-seq data available for one double minute chromosome offered additional support for our local tumor genome assemblies, and identified the birth of a novel exon made possible through rearranged sequences present in the double minute chromosomes. Our method was also useful for analysis of a larger set of glioblastoma multiforme tumors for which exome sequencing data are available, finding evidence for oncogenic double minute chromosomes in more than 20% of clinical specimens examined, a frequency consistent with previous estimates. Yes NA CTDB0282 Methodology 23972288 Chen K, Navin NE, Wang Y, Schmidt HK, Wallis JW, Niu B, Fan X, Zhao H, McLellan MD, Hoadley KA, Mardis ER, Ley TJ, Perou CM, Wilson RK, Ding L BreakTrans: uncovering the genomic architecture of gene fusions Genome Biology 2013 Aug 2 Breast cancer Next Generation Sequencing Homo sapiens A0YG PPP3R1;USP34;LTBP1;TTC27; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas 77030, USA Producing gene fusions through genomic structural rearrangements is a major mechanism for tumor evolution. Therefore, accurately detecting gene fusions and the originating rearrangements is of great importance for personalized cancer diagnosis and targeted therapy. We present a tool, BreakTrans, that systematically maps predicted gene fusions to structural rearrangements. Thus, BreakTrans not only validates both types of predictions, but also provides mechanistic interpretations. BreakTrans effectively validates known fusions and discovers novel events in a breast cancer cell line. Applying BreakTrans to 43 breast cancer samples in The Cancer Genome Atlas identifies 90 genomically validated gene fusions. BreakTrans is available at http://bioinformatics.mdanderson.org/main/BreakTrans. NCBI 36/hg18 phs000178 Yes PPP3R1,TTC27 CTDB0284 Research 24055055 Li S, Shen D, Shao J, Crowder R, Liu W, Prat A, He X, Liu S, Hoog J, Lu C, Ding L, Griffith OL, Miller C, Larson D, Fulton RS, Harrison M, Mooney T, McMichael JF, Luo J, Tao Y, Goncalves R, Schlosberg C, Hiken JF, Saied L, Sanchez C, Giuntoli T, Bumb C, Cooper C, Kitchens RT, Lin A, Phommaly C, Davies SR, Zhang J, Kavuri MS, McEachern D, Dong YY, Ma C, Pluard T, Naughton M, Bose R, Suresh R, McDowell R, Michel L, Aft R, Gillanders W, DeSchryver K, Wilson RK, Wang S, Mills GB, Gonzalez-Angulo A, Edwards JR, Maher C, Perou CM, Mardis ER, Ellis MJ Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts Cell Reports 2013 Sep 1,2,3,4,6,7,9,10,11,12,13,14,15,16,17,18,19,20,21,X Breast cancer Next Generation Sequencing Homo sapiens WHIM8 Illumina chr10:0-76919999:0;chr10:101490001-111219999:0;chr10:111220000-112660000:-1;chr10:112660001-135374737:0;chr10:76920000-80910000:1;chr10:76920000-80950000:1;chr10:80950001-80969999:0;chr10:80970000-81220000:1;chr10:81220001-81259999:0;chr10:81260000-81540000:1;chr10:81540001-81559999:0;chr10:81560000-82430000:1;chr10:82430001-82759999:0;chr10:82760000-83840000:-1;chr10:83840001-83849999:0;chr10:83850000-84890000:1;chr10:83860000-84890000:1;chr10:84890001-85149999:0;chr10:85150000-86220000:1;chr10:86220001-86239999:0;chr10:86240000-91130000:-1;chr10:91130001-91139999:0;chr10:91140000-93900000:1;chr10:91150000-94310000:1;chr10:94310001-94329999:0;chr10:94330000-101490000:-1;chr11:0-69999:0;chr11:14810000-16990000:-1;chr11:16990001-24279999:0;chr11:24280000-31320000:-1;chr11:270000-2010000:-1;chr11:31320001-36759999:0;chr11:3220001-3329999:0;chr11:3330000-4200000:-1;chr11:36760000-37290000:-1;chr11:37290001-37549999:0;chr11:37550000-42910000:-1;chr11:4200001-4299999:0;chr11:42910001-45329999:0;chr11:4300000-9660000:-1;chr11:45330000-47190000:-1;chr11:47190001-55219999:0;chr11:55220000-55550000:1;chr11:55550001-55569999:0;chr11:55570000-61310000:-1;chr11:61310001-134452384:0;chr11:70000-3220000:-1;chr11:9660001-14809999:0;chr12:0-64969999:0;chr12:120360000-121510000:-1;chr12:130830000-131990000:-1;chr12:132260001-132349534:0;chr12:64970000-74360000:-1;chr12:74360001-74369999:0;chr12:74370000-78630000:-1;chr12:74380000-78630000:-1;chr12:78630001-78649999:0;chr12:78650000-132260000:-1;chr13:0-17929999:0;chr13:17930000-55570000:-1;chr13:55570001-60399999:0;chr13:60400000-67060000:1;chr13:67060001-114142980:0;chr14:0-19499999:0;chr14:101400001-101799999:0;chr14:101800000-102780000:1;chr14:102780001-105609999:0;chr14:105610000-106340000:1;chr14:105640000-106340000:1;chr14:106340001-106368585:0;chr14:19500000-26220000:-1;chr14:26220001-26229999:0;chr14:26230000-32930000:1;chr14:26240000-32930000:1;chr14:32930001-32949999:0;chr14:32950000-36740000:-1;chr14:36740001-36749999:0;chr14:36750000-38780000:1;chr14:36760000-38790000:1;chr14:38790001-38809999:0;chr14:38810000-42880000:-1;chr14:42880001-42899999:0;chr14:42900000-43310000:-1;chr14:43310001-43329999:0;chr14:43330000-69720000:-1;chr14:69720001-70579999:0;chr14:70580000-78330000:-1;chr14:78330001-94499999:0;chr14:94500000-95010000:-1;chr14:95010001-97739999:0;chr14:97740000-101230000:1;chr14:97740000-101400000:1;chr15:0-18279999:0;chr15:100250001-100338915:0;chr15:18280000-18640000:-1;chr15:18640001-20219999:0;chr15:20220000-21060000:-1;chr15:21060001-21199999:0;chr15:21200000-26230000:-1;chr15:26230001-26619999:0;chr15:26620000-32470000:-1;chr15:32470001-32639999:0;chr15:32640000-41630000:-1;chr15:41630001-41779999:0;chr15:41780000-57200000:-1;chr15:57200001-57829999:0;chr15:57830000-62470000:-1;chr15:62470001-65219999:0;chr15:65220000-67050000:-1;chr15:67050001-74479999:0;chr15:74480000-80360000:-1;chr15:80360001-81019999:0;chr15:81020000-84910000:-1;chr15:84910001-84989999:0;chr15:84990000-86580000:-1;chr15:86580001-86729999:0;chr15:86730000-88020000:-1;chr15:88020001-88029999:0;chr15:88030000-88920000:1;chr15:88040000-88920000:1;chr15:88920001-90249999:0;chr15:90250000-91680000:1;chr15:90250000-91700000:1;chr15:91700001-92579999:0;chr15:92580000-94710000:1;chr15:94710001-95529999:0;chr15:95530000-97040000:1;chr15:97040001-98279999:0;chr15:98280000-100250000:1;chr15:98290000-100250000:1;chr16:0-3249999:0;chr16:3250000-3800000:-1;chr16:3800001-49069999:0;chr16:49070000-51800000:1;chr16:49080000-51700000:1;chr16:51800001-51819999:0;chr16:51820000-69390000:-1;chr16:69390001-69769999:0;chr16:69770000-72940000:-1;chr16:72940001-73029999:0;chr16:73030000-88800000:-1;chr16:86930000-88560000:-1;chr16:88800001-88827254:0;chr17:0-59999:0;chr17:16590001-16689999:0;chr17:16690000-18280000:-1;chr17:18280001-18419999:0;chr17:18420000-18860000:-1;chr17:18860001-19079999:0;chr17:19080000-21120000:-1;chr17:21120001-21139999:0;chr17:21140000-21290000:-1;chr17:21290001-21709999:0;chr17:2150000-2700000:-1;chr17:21710000-22150000:-1;chr17:21720000-22150000:-1;chr17:22150001-24659999:0;chr17:24660000-25940000:1;chr17:25940001-26079999:0;chr17:26080000-29200000:-1;chr17:29200001-29209999:0;chr17:29210000-30680000:1;chr17:29220000-30700000:1;chr17:30700001-30719999:0;chr17:30720000-31500000:-1;chr17:31500001-31899999:0;chr17:31900000-33350000:-1;chr17:33350001-33919999:0;chr17:33920000-35830000:1;chr17:34750000-35450000:1;chr17:35830001-35849999:0;chr17:35850000-36340000:-1;chr17:36340001-36549999:0;chr17:36550000-38590000:-1;chr17:38590001-38779999:0;chr17:38780000-40490000:-1;chr17:40490001-40499999:0;chr17:40500000-41150000:1;chr17:40510000-41150000:1;chr17:41150001-41169999:0;chr17:41170000-41510000:-1;chr17:41510001-41529999:0;chr17:41530000-41710000:-1;chr17:41710001-42149999:0;chr17:4190000-4920000:-1;chr17:42150000-44610000:-1;chr17:44610001-44719999:0;chr17:44720000-45050000:-1;chr17:45050001-45069999:0;chr17:45070000-46360000:1;chr17:46360001-48339999:0;chr17:48340000-48630000:1;chr17:48630001-49829999:0;chr17:49830000-50140000:1;chr17:50140001-52279999:0;chr17:52280000-57180000:1;chr17:52490000-56180000:1;chr17:57180001-57449999:0;chr17:57450000-58390000:-1;chr17:58390001-59199999:0;chr17:59200000-63420000:-1;chr17:60000-16590000:-1;chr17:63420001-64019999:0;chr17:640000-1900000:-1;chr17:64020000-64570000:-1;chr17:64030000-64570000:-1;chr17:64570001-64649999:0;chr17:64650000-65910000:-1;chr17:65910001-65929999:0;chr17:65930000-66390000:-1;chr17:66390001-66409999:0;chr17:66410000-68280000:-1;chr17:66420000-68280000:-1;chr17:68280001-69379999:0;chr17:69380000-74960000:-1;chr17:7000000-7690000:-1;chr17:70550000-71640000:-1;chr17:74960001-75239999:0;chr17:75240000-77300000:-1;chr17:76550000-77300000:-1;chr17:77300001-77539999:0;chr17:77540000-78620000:-1;chr17:78620001-78774742:0;chr18:0-18229999:0;chr18:18230000-24500000:-1;chr18:24500001-24519999:0;chr18:24520000-27170000:1;chr18:24540000-27170000:1;chr18:27170001-27189999:0;chr18:27190000-37320000:-1;chr18:37320001-37329999:0;chr18:37330000-38000000:1;chr18:37340000-38000000:1;chr18:38000001-38019999:0;chr18:38020000-38460000:-1;chr18:38460001-38479999:0;chr18:38480000-41890000:1;chr18:38480000-41960000:1;chr18:41960001-42279999:0;chr18:42280000-45170000:1;chr18:45170001-45189999:0;chr18:45190000-48610000:-1;chr18:48610001-48689999:0;chr18:48690000-51560000:-1;chr18:51560001-51569999:0;chr18:51570000-54220000:1;chr18:51580000-56330000:1;chr18:55310000-56330000:1;chr18:56330001-56839999:0;chr18:56840000-70260000:-1;chr18:70260001-72919999:0;chr18:72920000-76090000:1;chr18:72930000-75600000:1;chr18:75670000-76090000:1;chr18:76090001-76117153:0;chr19:0-439999:0;chr19:1230001-37639999:0;chr19:37640000-43850000:1;chr19:43850001-43869999:0;chr19:43870000-53090000:-1;chr19:43890000-44500000:-1;chr19:440000-1230000:-1;chr19:45340000-46000000:-1;chr19:49860000-51210000:-1;chr19:51490000-53090000:-1;chr19:53090001-53109999:0;chr19:53110000-53150000:-1;chr19:53150001-53169999:0;chr19:53170000-55980000:-1;chr19:53170000-63780000:-1;chr19:58730000-59410000:-1;chr19:59920000-60910000:-1;chr19:63780001-63811651:0;chr1:0-609999:0;chr1:1240001-1449999:0;chr1:144110000-144530000:1;chr1:144530001-144669999:0;chr1:144670000-145880000:1;chr1:144810000-145870000:1;chr1:1450000-3690000:-1;chr1:145880001-145969999:0;chr1:145970000-146290000:1;chr1:146290001-147309999:0;chr1:147310000-147460000:1;chr1:147460001-148029999:0;chr1:148030000-150100000:1;chr1:148030000-159710000:1;chr1:156470000-158100000:1;chr1:159710001-159769999:0;chr1:159770000-194900000:1;chr1:194900001-195089999:0;chr1:195090000-197900000:1;chr1:197900001-198039999:0;chr1:198040000-214280000:1;chr1:214280001-232309999:0;chr1:232310000-247170000:1;chr1:247170001-247249719:0;chr1:3690001-144109999:0;chr1:610000-1240000:-1;chr20:0-49009999:0;chr20:49010000-62410000:1;chr20:50280000-51500000:1;chr20:51910000-54340000:1;chr20:54970000-59500000:1;chr20:62410001-62435964:0;chr21:0-13379999:0;chr21:13380000-23200000:-1;chr21:23200001-34959999:0;chr21:34960000-46920000:1;chr21:34970000-36280000:1;chr21:37670000-39540000:1;chr21:39810000-41750000:1;chr21:42270000-42870000:1;chr21:46920001-46944323:0;chr22:0-49691432:0;chr2:0-121949999:0;chr2:121950000-130930000:-1;chr2:130930001-131029999:0;chr2:131030000-132470000:-1;chr2:132470001-132849999:0;chr2:132850000-231060000:-1;chr2:231060001-232129999:0;chr2:232130000-242160000:-1;chr2:242160001-242369999:0;chr2:242370000-242730000:-1;chr2:242730001-242951149:0;chr3:0-49999:0;chr3:101630001-102079999:0;chr3:102080000-102700000:-1;chr3:102700001-111079999:0;chr3:10300000-12550000:1;chr3:111080000-112730000:-1;chr3:112730001-117459999:0;chr3:117460000-121750000:-1;chr3:121750001-121909999:0;chr3:121910000-143150000:-1;chr3:12930000-17430000:1;chr3:143150001-143959999:0;chr3:143960000-147530000:-1;chr3:147530001-149039999:0;chr3:149040000-157470000:-1;chr3:157470001-160649999:0;chr3:160650000-163980000:-1;chr3:163980001-164119999:0;chr3:164120000-169700000:-1;chr3:169700001-169709999:0;chr3:169710000-170850000:1;chr3:169720000-171210000:1;chr3:171210001-171229999:0;chr3:171230000-180530000:-1;chr3:17430001-17449999:0;chr3:17450000-46320000:-1;chr3:180530001-180659999:0;chr3:180660000-196830000:-1;chr3:196830001-196889999:0;chr3:196890000-196950000:-1;chr3:196950001-196969999:0;chr3:196970000-199420000:-1;chr3:199420001-199501827:0;chr3:46320001-46479999:0;chr3:46480000-68000000:-1;chr3:48640000-49490000:-1;chr3:50000-17430000:1;chr3:50000-9510000:1;chr3:68000001-68159999:0;chr3:68160000-75750000:-1;chr3:75750001-75959999:0;chr3:75960000-76300000:-1;chr3:76300001-76489999:0;chr3:76490000-85260000:-1;chr3:85260001-85409999:0;chr3:85410000-90580000:-1;chr3:90580001-96099999:0;chr3:96100000-101630000:-1;chr4:0-639999:0;chr4:17180001-18929999:0;chr4:18930000-48770000:-1;chr4:190760001-191273063:0;chr4:3530001-3549999:0;chr4:3550000-3600000:-1;chr4:3600001-3619999:0;chr4:3620000-17180000:-1;chr4:48770001-52379999:0;chr4:52380000-68900000:-1;chr4:640000-3530000:-1;chr4:650000-1840000:-1;chr4:68900001-69639999:0;chr4:69640000-70150000:-1;chr4:70150001-70279999:0;chr4:70280000-190760000:-1;chr5:0-180857866:0;chr6:0-38029999:0;chr6:109910001-111279999:0;chr6:111280000-112780000:1;chr6:111770000-112770000:1;chr6:112780001-113149999:0;chr6:113150000-113620000:1;chr6:113620001-116319999:0;chr6:116320000-122850000:1;chr6:116320000-122860000:1;chr6:122860001-127069999:0;chr6:127070000-127980000:1;chr6:127980001-132309999:0;chr6:132310000-133500000:1;chr6:133500001-134419999:0;chr6:134420000-136680000:1;chr6:134700000-136680000:1;chr6:136680001-136699999:0;chr6:136700000-157500000:-1;chr6:157500001-157999999:0;chr6:158000000-167740000:-1;chr6:167740001-168349999:0;chr6:168350000-170790000:-1;chr6:170790001-170899992:0;chr6:38030000-39720000:-1;chr6:39720001-57729999:0;chr6:57730000-58190000:-1;chr6:58190001-70589999:0;chr6:70590000-88850000:-1;chr6:88850001-88859999:0;chr6:88860000-89530000:1;chr6:88870000-89530000:1;chr6:89530001-89549999:0;chr6:89550000-94070000:-1;chr6:94070001-94079999:0;chr6:94080000-109910000:1;chr6:94090000-109910000:1;chr7:0-15839999:0;chr7:121470000-122000000:1;chr7:121480000-121990000:1;chr7:122000001-136699999:0;chr7:136700000-137070000:1;chr7:137070001-140019999:0;chr7:140020000-141670000:1;chr7:140430000-141660000:1;chr7:141670001-142819999:0;chr7:142820000-143200000:1;chr7:143200001-144099999:0;chr7:144100000-146750000:1;chr7:146750001-146769999:0;chr7:146770000-151550000:-1;chr7:151550001-151629999:0;chr7:151630000-153760000:-1;chr7:153760001-153769999:0;chr7:153770000-155560000:1;chr7:153780000-155560000:1;chr7:155560001-155579999:0;chr7:155580000-158610000:-1;chr7:15840000-44950000:1;chr7:158610001-158821424:0;chr7:44950001-121469999:0;chr8:0-146274826:0;chr9:0-39999:0;chr9:117540001-133109999:0;chr9:133110000-135440000:-1;chr9:135440001-140273252:0;chr9:38790001-41889999:0;chr9:40000-38790000:-1;chr9:41890000-41970000:-1;chr9:41970001-41989999:0;chr9:41990000-42980000:-1;chr9:42980001-43339999:0;chr9:43340000-43790000:-1;chr9:43790001-67379999:0;chr9:67380000-67810000:-1;chr9:67810001-69139999:0;chr9:69140000-69470000:-1;chr9:69470001-69609999:0;chr9:69610000-117540000:-1;chrX:0-109999:0;chrX:110000-940000:-1;chrX:114850001-114869999:0;chrX:114870000-114910000:-1;chrX:114910001-114929999:0;chrX:114930000-119880000:-1;chrX:1150000-2240000:-1;chrX:1150000-3680000:-1;chrX:119880001-119959999:0;chrX:119960000-153060000:-1;chrX:152560000-153060000:-1;chrX:153060001-153179999:0;chrX:153180000-153710000:-1;chrX:153710001-153719999:0;chrX:153720000-154890000:1;chrX:153730000-154890000:1;chrX:154890001-154913754:0;chrX:3680001-3969999:0;chrX:3970000-49080000:-1;chrX:49080001-49099999:0;chrX:49100000-49250000:-1;chrX:49250001-49269999:0;chrX:49270000-52110000:-1;chrX:52110001-52589999:0;chrX:52590000-58570000:-1;chrX:58570001-61659999:0;chrX:61660000-66740000:-1;chrX:66740001-67159999:0;chrX:67160000-70600000:-1;chrX:70600001-72539999:0;chrX:72540000-76140000:-1;chrX:76140001-77339999:0;chrX:77340000-114850000:-1;chrX:940001-1149999:0;chrY:0-57772954:0 Section of Breast Oncology, Division of Oncology, Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation. NCBI 36/hg18 phs000611 Yes NA CTDB0285 Research 24055055 Li S, Shen D, Shao J, Crowder R, Liu W, Prat A, He X, Liu S, Hoog J, Lu C, Ding L, Griffith OL, Miller C, Larson D, Fulton RS, Harrison M, Mooney T, McMichael JF, Luo J, Tao Y, Goncalves R, Schlosberg C, Hiken JF, Saied L, Sanchez C, Giuntoli T, Bumb C, Cooper C, Kitchens RT, Lin A, Phommaly C, Davies SR, Zhang J, Kavuri MS, McEachern D, Dong YY, Ma C, Pluard T, Naughton M, Bose R, Suresh R, McDowell R, Michel L, Aft R, Gillanders W, DeSchryver K, Wilson RK, Wang S, Mills GB, Gonzalez-Angulo A, Edwards JR, Maher C, Perou CM, Mardis ER, Ellis MJ Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts Cell Reports 2013 Sep 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,X Breast cancer Next Generation Sequencing Homo sapiens WHIM18 Illumina chr10:0-32509999:0;chr10:109100000-109680000:1;chr10:109680001-117179999:0;chr10:117180000-117690000:1;chr10:117690001-135374737:0;chr10:32510000-38840000:-1;chr10:35070000-35660000:-1;chr10:38840001-42109999:0;chr10:42110000-45590000:-1;chr10:45590001-55739999:0;chr10:55740000-59390000:1;chr10:59390001-62499999:0;chr10:62500000-63190000:1;chr10:63190001-66119999:0;chr10:66120000-66780000:1;chr10:66780001-90109999:0;chr10:90110000-90710000:1;chr10:90710001-109099999:0;chr11:0-15949999:0;chr11:101360000-101820000:-1;chr11:101820001-106949999:0;chr11:106950000-108060000:-1;chr11:108060001-108339999:0;chr11:108340000-109010000:-1;chr11:109010001-111079999:0;chr11:111080000-111750000:-1;chr11:111750001-113009999:0;chr11:113010000-113510000:-1;chr11:113510001-115869999:0;chr11:115870000-124290000:-1;chr11:116380000-116960000:-1;chr11:117690000-119170000:-1;chr11:121930000-122990000:-1;chr11:124290001-124709999:0;chr11:124710000-125930000:-1;chr11:125930001-128679999:0;chr11:128680000-129820000:-1;chr11:129820001-132999999:0;chr11:133000000-134430000:-1;chr11:134430001-134452384:0;chr11:15950000-16450000:1;chr11:16450001-23519999:0;chr11:23520000-24620000:1;chr11:24620001-28509999:0;chr11:28510000-29610000:1;chr11:29610001-36879999:0;chr11:36880000-38690000:1;chr11:38690001-40749999:0;chr11:40750000-41400000:1;chr11:41400001-75519999:0;chr11:75520000-78090000:-1;chr11:76860000-77600000:-1;chr11:78090001-85239999:0;chr11:85240000-85740000:-1;chr11:85740001-86209999:0;chr11:86210000-87180000:-1;chr11:87180001-92799999:0;chr11:92800000-93800000:-1;chr11:93800001-97009999:0;chr11:97010000-98260000:-1;chr11:98260001-101359999:0;chr12:0-1679999:0;chr12:100880000-102650000:1;chr12:10130001-10299999:0;chr12:10300000-11960000:1;chr12:10320000-11970000:1;chr12:103680000-106220000:1;chr12:106770000-107210000:1;chr12:109270001-109859999:0;chr12:109860000-110160000:1;chr12:110160001-110779999:0;chr12:110780000-111270000:1;chr12:111270001-111499999:0;chr12:111500000-111960000:1;chr12:111960001-112399999:0;chr12:112400000-113540000:1;chr12:112950000-113290000:1;chr12:113540001-113749999:0;chr12:113750000-116850000:1;chr12:113830000-115180000:1;chr12:116850001-117069999:0;chr12:117070000-118770000:1;chr12:117580000-118030000:1;chr12:118770001-122859999:0;chr12:11970001-12989999:0;chr12:122860000-123980000:1;chr12:123980001-124149999:0;chr12:124150000-127860000:1;chr12:124380000-127060000:1;chr12:127860001-128089999:0;chr12:128090000-130820000:1;chr12:128180000-128820000:1;chr12:12990000-14150000:1;chr12:13050000-14160000:1;chr12:130820001-132349534:0;chr12:14160001-14409999:0;chr12:14410000-19300000:1;chr12:14410000-19310000:1;chr12:1680000-2760000:1;chr12:1830000-2590000:1;chr12:19300001-19679999:0;chr12:19680000-24920000:1;chr12:19710000-31250000:1;chr12:25080000-30990000:1;chr12:2760001-3289999:0;chr12:31250001-33029999:0;chr12:3290000-6020000:1;chr12:33030000-34230000:1;chr12:33290000-34080000:1;chr12:3350000-3880000:1;chr12:34230001-36679999:0;chr12:36680000-47790000:1;chr12:36850000-40810000:1;chr12:41280000-45840000:1;chr12:4430000-5980000:1;chr12:46030000-46400000:1;chr12:46690000-47190000:1;chr12:47790001-48029999:0;chr12:48030000-48940000:1;chr12:48940001-49189999:0;chr12:49190000-109270000:1;chr12:51010000-51450000:1;chr12:53270000-54300000:1;chr12:56630000-62800000:1;chr12:6020001-7149999:0;chr12:63510000-67210000:1;chr12:67580000-91780000:1;chr12:7150000-7540000:1;chr12:7210000-7620000:1;chr12:7620001-9029999:0;chr12:9030000-9430000:1;chr12:9050000-9430000:1;chr12:92500000-93390000:1;chr12:9430001-9629999:0;chr12:95460000-97300000:1;chr12:9630000-10130000:1;chr12:97640000-98970000:1;chr12:99120000-100750000:1;chr13:0-18349999:0;chr13:100900001-109169999:0;chr13:109170000-113650000:-1;chr13:112320000-113650000:-1;chr13:113650001-114142980:0;chr13:18350000-25010000:-1;chr13:25010001-25299999:0;chr13:25300000-28870000:-1;chr13:28870001-28889999:0;chr13:28890000-29810000:1;chr13:28890000-33380000:1;chr13:30350000-33380000:1;chr13:33380001-39739999:0;chr13:39740000-41050000:-1;chr13:41050001-43969999:0;chr13:43970000-44980000:-1;chr13:44980001-46779999:0;chr13:46780000-47800000:-1;chr13:47800001-48649999:0;chr13:48650000-49640000:-1;chr13:49640001-51479999:0;chr13:51480000-52320000:-1;chr13:52320001-93889999:0;chr13:93890000-96060000:-1;chr13:96060001-97019999:0;chr13:97020000-100900000:-1;chr13:97370000-98230000:-1;chr13:99010000-99560000:-1;chr14:0-18219999:0;chr14:18220000-19050000:1;chr14:18400000-19050000:1;chr14:19050001-19129999:0;chr14:19130000-20400000:1;chr14:20400001-21439999:0;chr14:21440000-22070000:1;chr14:21450000-22020000:1;chr14:22070001-24969999:0;chr14:24970000-27640000:1;chr14:27640001-29219999:0;chr14:29220000-30710000:1;chr14:29220000-31060000:1;chr14:31060001-32729999:0;chr14:32730000-33280000:1;chr14:33280001-39709999:0;chr14:39710000-42310000:1;chr14:42310001-43239999:0;chr14:43240000-43940000:1;chr14:43940001-45449999:0;chr14:45450000-46630000:1;chr14:46630001-81609999:0;chr14:81610000-83600000:1;chr14:83600001-106368585:0;chr15:0-20309999:0;chr15:100270001-100338915:0;chr15:20310000-20900000:-1;chr15:20900001-21199999:0;chr15:21200000-21930000:-1;chr15:21930001-22279999:0;chr15:22280000-26360000:-1;chr15:26360001-26639999:0;chr15:26640000-30640000:-1;chr15:30640001-31739999:0;chr15:31740000-32450000:-1;chr15:32450001-32649999:0;chr15:32650000-33180000:-1;chr15:33180001-35169999:0;chr15:35170000-35630000:-1;chr15:35630001-38129999:0;chr15:38130000-44240000:-1;chr15:38310000-40090000:-1;chr15:40460000-41980000:-1;chr15:42260000-43780000:-1;chr15:44240001-48219999:0;chr15:48220000-49170000:-1;chr15:48400000-49000000:-1;chr15:49170001-49659999:0;chr15:49660000-50660000:-1;chr15:50660001-52489999:0;chr15:52490000-55500000:-1;chr15:55500001-56419999:0;chr15:56420000-58510000:-1;chr15:56820000-57700000:-1;chr15:58510001-60239999:0;chr15:60240000-67050000:-1;chr15:61910000-63640000:-1;chr15:63850000-64950000:-1;chr15:67050001-69779999:0;chr15:69780000-73310000:-1;chr15:71740000-73310000:-1;chr15:73310001-73379999:0;chr15:73380000-78260000:-1;chr15:75600000-77110000:-1;chr15:78260001-79669999:0;chr15:79670000-80360000:-1;chr15:80360001-80999999:0;chr15:81000000-81570000:-1;chr15:81000000-82370000:-1;chr15:82370001-82679999:0;chr15:82680000-83540000:-1;chr15:83540001-83609999:0;chr15:83610000-84380000:-1;chr15:84380001-86559999:0;chr15:86560000-89570000:-1;chr15:86880000-89400000:-1;chr15:89570001-90939999:0;chr15:90940000-93640000:-1;chr15:93640001-94669999:0;chr15:94670000-97050000:-1;chr15:97050001-97299999:0;chr15:97300000-100270000:-1;chr16:0-480000:1;chr16:1040000-1440000:1;chr16:10850000-11160000:1;chr16:12130000-12680000:1;chr16:12910000-14270000:1;chr16:1440001-1929999:0;chr16:14930001-15039999:0;chr16:15040000-16300000:1;chr16:16300001-16389999:0;chr16:16390000-22470000:1;chr16:16530000-18280000:1;chr16:18410000-18810000:1;chr16:19040000-21250000:1;chr16:1930000-2230000:1;chr16:21340000-22030000:1;chr16:2230001-2249999:0;chr16:22470001-22629999:0;chr16:2250000-2940000:1;chr16:22630000-23180000:1;chr16:22630000-28250000:1;chr16:23760000-24480000:1;chr16:24850000-27050000:1;chr16:28250001-29079999:0;chr16:29080000-29480000:1;chr16:2940001-3059999:0;chr16:29480001-31409999:0;chr16:3060000-14930000:1;chr16:31410000-31940000:1;chr16:31490000-31940000:1;chr16:31940001-34059999:0;chr16:34060000-35020000:1;chr16:34060000-35070000:1;chr16:35020001-45069999:0;chr16:45070000-50120000:-1;chr16:480001-1039999:0;chr16:48210000-48900000:-1;chr16:50120001-51519999:0;chr16:51520000-52210000:-1;chr16:52210001-52779999:0;chr16:5240000-8560000:1;chr16:52780000-53670000:-1;chr16:53670001-54909999:0;chr16:54910000-58920000:-1;chr16:55110000-57390000:-1;chr16:58920001-60879999:0;chr16:60880000-61850000:-1;chr16:61850001-64799999:0;chr16:64800000-69390000:-1;chr16:64850000-69390000:-1;chr16:69390001-69769999:0;chr16:69770000-74840000:-1;chr16:69930000-70650000:-1;chr16:72850000-74300000:-1;chr16:74840001-75679999:0;chr16:75680000-78190000:-1;chr16:78190001-79439999:0;chr16:79440000-80630000:-1;chr16:79610000-80500000:-1;chr16:80630001-81429999:0;chr16:81430000-84170000:-1;chr16:82390000-84170000:-1;chr16:84170001-84269999:0;chr16:84270000-86920000:-1;chr16:86920001-88827254:0;chr16:9220000-10200000:1;chr17:0-59999:0;chr17:12980001-78774742:0;chr17:3350000-8280000:-1;chr17:60000-12980000:-1;chr17:60000-2890000:-1;chr17:8470000-10200000:-1;chr18:0-69999:0;chr18:1140001-2479999:0;chr18:24330000-26920000:1;chr18:2480000-3780000:-1;chr18:26920001-28749999:0;chr18:28750000-30370000:1;chr18:30370001-33919999:0;chr18:33920000-35170000:1;chr18:35170001-35399999:0;chr18:35400000-37630000:1;chr18:37630001-38579999:0;chr18:3780001-24329999:0;chr18:38580000-40110000:1;chr18:40110001-60649999:0;chr18:60650000-64110000:1;chr18:64110001-64579999:0;chr18:64580000-65160000:1;chr18:65160001-76117153:0;chr18:70000-1140000:-1;chr19:0-9749999:0;chr19:11610001-16039999:0;chr19:16040000-19720000:-1;chr19:19720001-43259999:0;chr19:43260000-44440000:-1;chr19:44440001-49879999:0;chr19:49880000-51210000:-1;chr19:51210001-53459999:0;chr19:53460000-55270000:-1;chr19:55270001-63811651:0;chr19:9750000-11610000:-1;chr1:0-3649999:0;chr1:100660001-108579999:0;chr1:10610001-10689999:0;chr1:10690000-12250000:-1;chr1:10690000-13250000:-1;chr1:108580000-109320000:-1;chr1:109320001-109509999:0;chr1:109510000-110320000:-1;chr1:110320001-112489999:0;chr1:112490000-115310000:-1;chr1:112800000-113490000:-1;chr1:115310001-144109999:0;chr1:12470000-13250000:-1;chr1:13250001-13669999:0;chr1:13670000-16690000:-1;chr1:144110000-144530000:1;chr1:144530001-144669999:0;chr1:144670000-145880000:1;chr1:144810000-145870000:1;chr1:145880001-148029999:0;chr1:148030000-152050000:1;chr1:14910000-16690000:-1;chr1:150150000-151660000:1;chr1:152050001-152389999:0;chr1:152390000-159790000:1;chr1:155200000-156210000:1;chr1:156380000-158310000:1;chr1:159790001-159889999:0;chr1:159890000-173520000:1;chr1:159970000-160640000:1;chr1:160850000-163850000:1;chr1:164190000-165650000:1;chr1:166480000-169570000:1;chr1:16690001-17109999:0;chr1:169940000-171910000:1;chr1:17110000-18080000:-1;chr1:17110000-24120000:-1;chr1:172440000-172980000:1;chr1:173190000-173520000:1;chr1:173520001-174029999:0;chr1:174030000-194980000:1;chr1:174040000-176710000:1;chr1:177730000-178350000:1;chr1:178510000-179120000:1;chr1:179480000-180470000:1;chr1:180680000-181380000:1;chr1:181670000-194980000:1;chr1:19400000-20080000:-1;chr1:194980001-195089999:0;chr1:195090000-197900000:1;chr1:197900001-198039999:0;chr1:198040000-222370000:1;chr1:204980000-205750000:1;chr1:205820000-209390000:1;chr1:211230000-218250000:1;chr1:21270000-22610000:-1;chr1:218380000-220690000:1;chr1:220790000-221700000:1;chr1:222370001-222529999:0;chr1:222530000-233520000:1;chr1:222770000-223670000:1;chr1:226810000-227280000:1;chr1:22720000-24120000:-1;chr1:227900000-228430000:1;chr1:228640000-229210000:1;chr1:229850000-233050000:1;chr1:233520001-233669999:0;chr1:233670000-240120000:1;chr1:235460000-238250000:1;chr1:239010000-240070000:1;chr1:240120001-240289999:0;chr1:240290000-242940000:1;chr1:240350000-241080000:1;chr1:24120001-24249999:0;chr1:241350000-242430000:1;chr1:24250000-25450000:-1;chr1:242940001-243059999:0;chr1:243060000-247170000:1;chr1:243950000-244580000:1;chr1:245690000-246960000:1;chr1:247170001-247249719:0;chr1:25450001-25549999:0;chr1:25550000-29750000:-1;chr1:25550000-33580000:-1;chr1:30880000-33560000:-1;chr1:33580001-34969999:0;chr1:34970000-41820000:-1;chr1:35070000-36860000:-1;chr1:3650000-6390000:-1;chr1:37620000-38370000:-1;chr1:39040000-41260000:-1;chr1:41820001-42599999:0;chr1:42600000-47690000:-1;chr1:42940000-44480000:-1;chr1:44710000-46850000:-1;chr1:47690001-49489999:0;chr1:49490000-50210000:-1;chr1:50210001-50569999:0;chr1:50570000-55290000:-1;chr1:52080000-55140000:-1;chr1:55290001-61839999:0;chr1:61840000-63050000:-1;chr1:61890000-62670000:-1;chr1:63050001-67359999:0;chr1:6390001-6499999:0;chr1:6500000-10610000:-1;chr1:6500000-7130000:-1;chr1:67360000-67870000:-1;chr1:67870001-77679999:0;chr1:7400000-8340000:-1;chr1:77680000-78590000:-1;chr1:78590001-90939999:0;chr1:8740000-10610000:-1;chr1:90940000-93740000:-1;chr1:93740001-99989999:0;chr1:99990000-100660000:-1;chr20:0-19999:0;chr20:13930000-17530000:1;chr20:18600000-19780000:1;chr20:19910000-21140000:1;chr20:20000-2960000:1;chr20:21240000-24680000:1;chr20:25800001-29719999:0;chr20:2960001-3199999:0;chr20:29720000-30620000:1;chr20:30620001-30999999:0;chr20:31000000-31430000:1;chr20:31430001-31589999:0;chr20:31590000-32260000:1;chr20:3200000-3650000:1;chr20:32260001-32439999:0;chr20:32440000-34350000:1;chr20:34350001-35219999:0;chr20:35220000-41490000:1;chr20:3650001-3839999:0;chr20:37200000-38960000:1;chr20:3840000-4880000:1;chr20:39470000-41310000:1;chr20:41490001-41779999:0;chr20:41780000-45410000:1;chr20:45410001-45629999:0;chr20:45630000-47150000:1;chr20:47150001-47289999:0;chr20:47290000-47920000:1;chr20:47920001-48269999:0;chr20:48270000-49650000:1;chr20:4880001-5039999:0;chr20:49650001-50179999:0;chr20:50180000-51500000:1;chr20:50310000-51340000:1;chr20:5040000-5520000:1;chr20:51500001-51829999:0;chr20:51830000-54510000:1;chr20:51910000-54320000:1;chr20:54510001-54719999:0;chr20:54720000-59920000:1;chr20:5520001-5739999:0;chr20:5740000-25800000:1;chr20:57690000-59020000:1;chr20:59920001-60309999:0;chr20:60310000-60930000:1;chr20:6080000-13530000:1;chr20:60930001-62435964:0;chr20:990000-1720000:1;chr21:0-13379999:0;chr21:13380000-14010000:-1;chr21:14010001-17389999:0;chr21:17390000-18320000:-1;chr21:18320001-31229999:0;chr21:31230000-34360000:-1;chr21:31600000-32320000:-1;chr21:33310000-34280000:-1;chr21:34360001-36079999:0;chr21:36080000-37660000:-1;chr21:36280000-37330000:-1;chr21:37660001-39009999:0;chr21:39010000-44460000:-1;chr21:41660000-44460000:-1;chr21:44460001-44589999:0;chr21:44590000-45640000:-1;chr21:45640001-45809999:0;chr21:45810000-46920000:-1;chr21:46920001-46944323:0;chr22:0-15889999:0;chr22:15890000-17140000:-1;chr22:15910000-17140000:-1;chr22:17140001-17269999:0;chr22:17270000-18070000:-1;chr22:18070001-19019999:0;chr22:19020000-19800000:-1;chr22:19020000-19890000:-1;chr22:19890001-20249999:0;chr22:20250000-20920000:-1;chr22:20920001-20999999:0;chr22:21000000-22660000:-1;chr22:21730000-22660000:-1;chr22:22660001-22739999:0;chr22:22740000-24210000:-1;chr22:22740000-44640000:-1;chr22:27310000-28680000:-1;chr22:28920000-31380000:-1;chr22:34750000-38450000:-1;chr22:38670000-42290000:-1;chr22:42520000-44440000:-1;chr22:44640001-44769999:0;chr22:44770000-46170000:-1;chr22:44770000-48680000:-1;chr22:47070000-48680000:-1;chr22:48680001-49691432:0;chr2:0-269999:0;chr2:100300000-101750000:-1;chr2:10050000-11220000:-1;chr2:101010000-101720000:-1;chr2:101750001-104699999:0;chr2:104700000-107900000:-1;chr2:107900001-108379999:0;chr2:108380000-109810000:-1;chr2:109810001-112289999:0;chr2:112290000-113320000:-1;chr2:113320001-114089999:0;chr2:114090000-114880000:-1;chr2:114880001-116279999:0;chr2:116280000-118400000:-1;chr2:118400001-119309999:0;chr2:119310000-122640000:-1;chr2:12000001-15579999:0;chr2:120690000-121820000:-1;chr2:122640001-127239999:0;chr2:127240000-131050000:-1;chr2:128000000-129160000:-1;chr2:131050001-131139999:0;chr2:131140000-132020000:-1;chr2:132020001-134979999:0;chr2:134980000-136830000:-1;chr2:136830001-151739999:0;chr2:151740000-152910000:-1;chr2:152910001-159369999:0;chr2:15580000-16170000:-1;chr2:159370000-160410000:-1;chr2:160410001-169889999:0;chr2:16170001-23189999:0;chr2:169890000-170550000:-1;chr2:170550001-171169999:0;chr2:171170000-173300000:-1;chr2:173300001-197159999:0;chr2:197160000-198350000:-1;chr2:198350001-201379999:0;chr2:201380000-204330000:-1;chr2:202520000-204230000:-1;chr2:204330001-206429999:0;chr2:206430000-207010000:-1;chr2:207010001-208009999:0;chr2:208010000-208890000:-1;chr2:208890001-218359999:0;chr2:218360000-220470000:-1;chr2:218470000-220210000:-1;chr2:220470001-227579999:0;chr2:227580000-237090000:-1;chr2:231750000-232540000:-1;chr2:23190000-27920000:-1;chr2:237090001-238109999:0;chr2:238110000-242130000:-1;chr2:238430000-239140000:-1;chr2:239420000-240540000:-1;chr2:240690000-242130000:-1;chr2:242130001-242951149:0;chr2:24850000-27870000:-1;chr2:270000-4980000:-1;chr2:27920001-28289999:0;chr2:28290000-29380000:-1;chr2:28410000-29140000:-1;chr2:29380001-31649999:0;chr2:31650000-34730000:-1;chr2:34730001-36839999:0;chr2:36840000-37310000:-1;chr2:37310001-38379999:0;chr2:38380000-39700000:-1;chr2:38400000-38970000:-1;chr2:39700001-42039999:0;chr2:42040000-45200000:-1;chr2:42450000-43380000:-1;chr2:45200001-46839999:0;chr2:46840000-48730000:-1;chr2:46960000-47940000:-1;chr2:48730001-53729999:0;chr2:4980001-5719999:0;chr2:53730000-54340000:-1;chr2:54340001-55129999:0;chr2:55130000-55750000:-1;chr2:55750001-60629999:0;chr2:5720000-6510000:-1;chr2:60630000-63710000:-1;chr2:60730000-61260000:-1;chr2:61450000-62490000:-1;chr2:63710001-64879999:0;chr2:64880000-65740000:-1;chr2:65090000-65660000:-1;chr2:6510001-9059999:0;chr2:65740001-67959999:0;chr2:67960000-68620000:-1;chr2:68620001-69319999:0;chr2:69320000-71690000:-1;chr2:71690001-72699999:0;chr2:72700000-74630000:-1;chr2:73830000-74630000:-1;chr2:74630001-84819999:0;chr2:84820000-87410000:-1;chr2:84950000-86240000:-1;chr2:87410001-88029999:0;chr2:88030000-88840000:-1;chr2:88840001-95989999:0;chr2:9060000-12000000:-1;chr2:9150000-9870000:-1;chr2:95990000-97040000:-1;chr2:96110000-97030000:-1;chr2:97040001-97499999:0;chr2:97500000-99720000:-1;chr2:99720001-100299999:0;chr3:0-49999:0;chr3:103380000-106100000:1;chr3:106100001-106319999:0;chr3:106320000-106770000:1;chr3:106770001-111289999:0;chr3:111290000-112080000:1;chr3:112080001-115559999:0;chr3:115560000-116330000:1;chr3:116330001-117749999:0;chr3:117750000-119500000:1;chr3:119500001-145419999:0;chr3:145420000-148540000:1;chr3:148540001-149189999:0;chr3:149190000-150030000:1;chr3:150030001-162579999:0;chr3:162580000-163980000:1;chr3:163980001-164729999:0;chr3:164730000-166450000:1;chr3:1650001-17969999:0;chr3:166450001-167239999:0;chr3:167240000-170660000:1;chr3:170660001-174659999:0;chr3:174660000-175530000:1;chr3:175530001-176059999:0;chr3:176060000-177840000:1;chr3:177840001-179159999:0;chr3:179160000-179710000:1;chr3:17970000-18920000:1;chr3:179710001-191529999:0;chr3:18920001-21779999:0;chr3:191530000-192050000:1;chr3:192050001-199501827:0;chr3:21780000-22370000:1;chr3:22370001-24309999:0;chr3:24310000-25140000:1;chr3:25140001-29849999:0;chr3:29850000-30380000:1;chr3:30380001-35319999:0;chr3:35320000-35980000:1;chr3:35980001-70149999:0;chr3:50000-1650000:1;chr3:70150000-70760000:1;chr3:70760001-76489999:0;chr3:76490000-77030000:1;chr3:77030001-77549999:0;chr3:77550000-80890000:1;chr3:80890001-81119999:0;chr3:81120000-81720000:1;chr3:81720001-81949999:0;chr3:81950000-84670000:1;chr3:84670001-85099999:0;chr3:85100000-87430000:1;chr3:87430001-88439999:0;chr3:88440000-89860000:1;chr3:89860001-95519999:0;chr3:95520000-96810000:1;chr3:96810001-97099999:0;chr3:97100000-99350000:1;chr3:99350001-103379999:0;chr4:0-27149999:0;chr4:115830000-118730000:1;chr4:118730001-125529999:0;chr4:125530000-126670000:1;chr4:126670001-130279999:0;chr4:130280000-132180000:1;chr4:132180001-133539999:0;chr4:133540000-138450000:1;chr4:138450001-157659999:0;chr4:157660000-158610000:1;chr4:158610001-178029999:0;chr4:178030000-180900000:-1;chr4:180900001-182709999:0;chr4:182710000-190760000:-1;chr4:189070000-189600000:-1;chr4:190760001-191273063:0;chr4:27150000-27980000:1;chr4:27980001-28149999:0;chr4:28150000-29230000:1;chr4:29230001-31739999:0;chr4:31740000-32830000:1;chr4:32830001-33079999:0;chr4:33080000-34900000:1;chr4:34900001-35089999:0;chr4:35090000-35910000:1;chr4:35910001-59079999:0;chr4:59080000-59840000:1;chr4:59840001-65419999:0;chr4:65420000-66230000:1;chr4:66230001-69639999:0;chr4:69640000-70350000:1;chr4:70350001-80509999:0;chr4:80510000-81060000:1;chr4:81060001-93329999:0;chr4:93330000-94670000:1;chr4:94670001-96969999:0;chr4:96970000-97510000:1;chr4:97510001-97799999:0;chr4:97800000-98340000:1;chr4:98340001-115829999:0;chr5:0-1359999:0;chr5:10040000-10730000:-1;chr5:10730001-14489999:0;chr5:118200000-118810000:-1;chr5:118810001-125779999:0;chr5:125780000-126240000:-1;chr5:126240001-129509999:0;chr5:129510000-132580000:-1;chr5:132580001-133219999:0;chr5:133220000-134510000:-1;chr5:133280000-134430000:-1;chr5:134510001-136859999:0;chr5:1360000-7350000:-1;chr5:136860000-137890000:-1;chr5:137360000-137890000:-1;chr5:137890001-137959999:0;chr5:137960000-138800000:-1;chr5:138800001-138969999:0;chr5:138970000-142530000:1;chr5:140120000-140740000:1;chr5:142050000-142530000:1;chr5:142530001-147329999:0;chr5:14490000-15070000:-1;chr5:147330000-147870000:1;chr5:147870001-148999999:0;chr5:149000000-153240000:1;chr5:15070001-16649999:0;chr5:151150000-153230000:1;chr5:153240001-158589999:0;chr5:158590000-159310000:1;chr5:158590000-159450000:1;chr5:159450001-159609999:0;chr5:159610000-176310000:1;chr5:159730000-166090000:1;chr5:166300000-167580000:1;chr5:16650000-17290000:-1;chr5:16650000-17560000:-1;chr5:168140000-170630000:1;chr5:172780000-173800000:1;chr5:174300000-174790000:1;chr5:17560001-25009999:0;chr5:176310001-176879999:0;chr5:176880000-177210000:1;chr5:177210001-177539999:0;chr5:177540000-178290000:1;chr5:178290001-180857866:0;chr5:25010000-26430000:-1;chr5:26430001-31529999:0;chr5:31530000-33590000:-1;chr5:31560000-32620000:-1;chr5:33590001-34239999:0;chr5:34240000-35070000:-1;chr5:35070001-37049999:0;chr5:37050000-37720000:-1;chr5:37720001-40539999:0;chr5:40540000-41280000:-1;chr5:41280001-42919999:0;chr5:42920000-43550000:-1;chr5:43550001-45709999:0;chr5:45710000-46440000:-1;chr5:46440001-49459999:0;chr5:49460000-49990000:-1;chr5:49990001-52809999:0;chr5:52810000-53990000:-1;chr5:53990001-54459999:0;chr5:54460000-55570000:-1;chr5:55570001-59859999:0;chr5:59860000-60330000:-1;chr5:60330001-61489999:0;chr5:61490000-62310000:-1;chr5:62310001-64699999:0;chr5:64700000-65470000:-1;chr5:65470001-68249999:0;chr5:68250000-68890000:-1;chr5:68360000-68890000:-1;chr5:68890001-72039999:0;chr5:72040000-72900000:-1;chr5:72900001-73909999:0;chr5:7350001-10039999:0;chr5:73910000-80740000:-1;chr5:80740001-118199999:0;chr6:0-47839999:0;chr6:105210000-105820000:-1;chr6:105820001-106459999:0;chr6:106460000-112090000:-1;chr6:112090001-134389999:0;chr6:134390000-135300000:-1;chr6:135300001-136649999:0;chr6:136650000-137460000:-1;chr6:137460001-138629999:0;chr6:138630000-139960000:-1;chr6:139960001-144079999:0;chr6:144080000-144890000:-1;chr6:144890001-147759999:0;chr6:147760000-151950000:-1;chr6:149790000-150560000:-1;chr6:151060000-151890000:-1;chr6:151950001-154439999:0;chr6:154440000-155620000:-1;chr6:155620001-156329999:0;chr6:156330000-157500000:-1;chr6:157500001-157999999:0;chr6:158000000-164340000:-1;chr6:158290000-159290000:-1;chr6:164340001-165929999:0;chr6:165930000-167740000:-1;chr6:167740001-168049999:0;chr6:168050000-170630000:-1;chr6:170630001-170899992:0;chr6:47840000-49120000:1;chr6:49120001-49889999:0;chr6:49890000-50680000:1;chr6:50680001-51199999:0;chr6:51200000-51800000:1;chr6:51800001-56719999:0;chr6:56720000-57300000:-1;chr6:57300001-57939999:0;chr6:57940000-58880000:-1;chr6:58880001-61949999:0;chr6:61950000-62380000:-1;chr6:62380001-71079999:0;chr6:71080000-71740000:-1;chr6:71740001-73929999:0;chr6:73930000-75280000:-1;chr6:73960000-74470000:-1;chr6:75280001-76299999:0;chr6:76300000-77150000:-1;chr6:77150001-78459999:0;chr6:78460000-79700000:-1;chr6:79700001-84009999:0;chr6:84010000-90820000:-1;chr6:90820001-105209999:0;chr7:0-8449999:0;chr7:101900001-102119999:0;chr7:102120000-105660000:-1;chr7:10350001-11089999:0;chr7:105660001-106079999:0;chr7:106080000-106530000:-1;chr7:106530001-111189999:0;chr7:11090000-12400000:1;chr7:111190000-127440000:1;chr7:111200000-123850000:1;chr7:12400001-14079999:0;chr7:124370000-127880000:1;chr7:127880001-128009999:0;chr7:128010000-129340000:1;chr7:129340001-129509999:0;chr7:129510000-137460000:1;chr7:131080000-132410000:1;chr7:132600000-134770000:1;chr7:135260000-137300000:1;chr7:137460001-138149999:0;chr7:138150000-139660000:1;chr7:139660001-139999999:0;chr7:140000000-141290000:1;chr7:140430000-141290000:1;chr7:14080000-15780000:1;chr7:141290001-143209999:0;chr7:143210000-147570000:1;chr7:143210000-148280000:1;chr7:148280001-148529999:0;chr7:148530000-150260000:1;chr7:150260001-150429999:0;chr7:150430000-151380000:1;chr7:151380001-152089999:0;chr7:152090000-154920000:1;chr7:152460000-153200000:1;chr7:154920001-155799999:0;chr7:155800000-156360000:1;chr7:156360001-157359999:0;chr7:157360000-158610000:1;chr7:15780001-16979999:0;chr7:158610001-158821424:0;chr7:16980000-17550000:1;chr7:17550001-18199999:0;chr7:18200000-18960000:1;chr7:18960001-19259999:0;chr7:19260000-19830000:1;chr7:19830001-53109999:0;chr7:53110000-53980000:1;chr7:53980001-72239999:0;chr7:72240000-73710000:-1;chr7:73710001-77829999:0;chr7:77830000-79320000:1;chr7:79320001-79609999:0;chr7:79610000-80140000:1;chr7:80140001-80709999:0;chr7:80710000-81700000:1;chr7:81700001-82129999:0;chr7:82130000-85580000:1;chr7:8450000-10350000:1;chr7:85580001-87799999:0;chr7:87800000-89520000:1;chr7:89520001-92629999:0;chr7:92630000-94110000:1;chr7:94110001-98389999:0;chr7:98390000-98990000:-1;chr7:98400000-101900000:-1;chr7:99380000-101900000:-1;chr8:0-149999:0;chr8:102220000-103440000:1;chr8:104110000-120880000:1;chr8:11940001-12509999:0;chr8:121210000-123850000:1;chr8:124640000-125430000:1;chr8:12510000-16300000:1;chr8:125930000-126340000:1;chr8:126710000-127470000:1;chr8:127670000-128750000:1;chr8:129110000-130990000:1;chr8:13100000-16300000:1;chr8:131610000-134520000:1;chr8:134750000-139900000:1;chr8:140050000-140680000:1;chr8:141490001-141719999:0;chr8:141720000-142140000:1;chr8:142140001-142529999:0;chr8:142530000-143510000:1;chr8:143510001-143699999:0;chr8:143700000-143980000:1;chr8:143980001-146274826:0;chr8:150000-2170000:1;chr8:16300001-16379999:0;chr8:16380000-20120000:1;chr8:16380000-21940000:1;chr8:20300000-21550000:1;chr8:2170001-2279999:0;chr8:21940001-22329999:0;chr8:22330000-30620000:1;chr8:2280000-5970000:1;chr8:2280000-6030000:1;chr8:23500000-24900000:1;chr8:25330000-25940000:1;chr8:26600000-27330000:1;chr8:29450000-29940000:1;chr8:30620001-30769999:0;chr8:30770000-33390000:1;chr8:30970000-33330000:1;chr8:33390001-33639999:0;chr8:33640000-37750000:1;chr8:33720000-37480000:1;chr8:37750001-38179999:0;chr8:38180000-42560000:1;chr8:38980000-39880000:1;chr8:40040000-40840000:1;chr8:42560001-42819999:0;chr8:42820000-43600000:1;chr8:43200000-43900000:1;chr8:43900001-47089999:0;chr8:47090000-48240000:1;chr8:47480000-48150000:1;chr8:48240001-48409999:0;chr8:48410000-70890000:1;chr8:49270000-54900000:1;chr8:55570000-56780000:1;chr8:57200000-66590000:1;chr8:6030001-6239999:0;chr8:6240000-7000000:1;chr8:66790000-67490000:1;chr8:68520000-70890000:1;chr8:7000001-8019999:0;chr8:70890001-71179999:0;chr8:71180000-86730000:1;chr8:71200000-74750000:1;chr8:75130000-81200000:1;chr8:8020000-11940000:1;chr8:81570000-86730000:1;chr8:86730001-86919999:0;chr8:86920000-95540000:1;chr8:86920000-98710000:1;chr8:96190000-98610000:1;chr8:98710001-98889999:0;chr8:9880000-10350000:1;chr8:98890000-141490000:1;chr8:99270000-101660000:1;chr9:0-39999:0;chr9:100800001-101839999:0;chr9:101840000-102790000:-1;chr9:102790001-106429999:0;chr9:106430000-107700000:-1;chr9:107700001-109049999:0;chr9:109050000-109700000:-1;chr9:109700001-110799999:0;chr9:110800000-114810000:-1;chr9:114810001-114899999:0;chr9:114900000-116560000:-1;chr9:116560001-122279999:0;chr9:1200001-4379999:0;chr9:122280000-125320000:-1;chr9:125320001-125709999:0;chr9:125710000-135370000:-1;chr9:126570000-127240000:-1;chr9:129160000-133740000:-1;chr9:133990000-135370000:-1;chr9:135370001-136509999:0;chr9:136510000-137700000:-1;chr9:137700001-139489999:0;chr9:139490000-140160000:-1;chr9:140160001-140273252:0;chr9:14830000-15810000:-1;chr9:15810001-16679999:0;chr9:16680000-17360000:-1;chr9:17360001-18869999:0;chr9:18870000-19560000:-1;chr9:19560001-23839999:0;chr9:23840000-25150000:-1;chr9:25150001-26739999:0;chr9:26740000-27350000:-1;chr9:27350001-32439999:0;chr9:32440000-38810000:-1;chr9:33790000-34710000:-1;chr9:36090000-36650000:-1;chr9:38810001-66509999:0;chr9:40000-1200000:-1;chr9:4380000-6860000:-1;chr9:66510000-66670000:-1;chr9:66670001-70679999:0;chr9:6860001-14829999:0;chr9:70680000-71340000:-1;chr9:71340001-71969999:0;chr9:71970000-72540000:-1;chr9:72540001-73379999:0;chr9:73380000-74440000:-1;chr9:74440001-76559999:0;chr9:76560000-80250000:-1;chr9:80250001-83269999:0;chr9:83270000-83780000:-1;chr9:83780001-85129999:0;chr9:85130000-86340000:-1;chr9:86340001-87469999:0;chr9:87470000-91660000:-1;chr9:89710000-90380000:-1;chr9:91660001-92829999:0;chr9:92830000-100800000:-1;chr9:94440000-95150000:-1;chr9:98020000-98530000:-1;chrX:0-269999:0;chrX:100130000-100730000:-1;chrX:100730001-104529999:0;chrX:104530000-105080000:1;chrX:105080001-106789999:0;chrX:106790000-109090000:1;chrX:106920000-109090000:1;chrX:109090001-111969999:0;chrX:111970000-114850000:-1;chrX:114850001-114929999:0;chrX:114930000-118280000:-1;chrX:118280001-118989999:0;chrX:118990000-119880000:1;chrX:119040000-119470000:1;chrX:119880001-119959999:0;chrX:119960000-120280000:1;chrX:120280001-120789999:0;chrX:120790000-122600000:1;chrX:120790000-122680000:1;chrX:122680001-122929999:0;chrX:122930000-123270000:1;chrX:123270001-123569999:0;chrX:123570000-128540000:1;chrX:123890000-134710000:1;chrX:1290000-1430000:-1;chrX:129280000-132340000:1;chrX:132520000-133280000:1;chrX:133970000-134710000:1;chrX:134710001-134749999:0;chrX:134750000-141460000:1;chrX:135220000-135660000:1;chrX:135930000-136440000:1;chrX:136690000-138750000:1;chrX:139010000-140380000:1;chrX:140480000-141460000:1;chrX:141460001-142819999:0;chrX:142820000-147270000:-1;chrX:1430001-1509999:0;chrX:147270001-148139999:0;chrX:148140000-149660000:1;chrX:148140000-152350000:1;chrX:149990000-151730000:1;chrX:1510000-3680000:-1;chrX:152350001-153469999:0;chrX:153470000-154890000:1;chrX:153550000-154890000:1;chrX:154890001-154913754:0;chrX:25240000-30960000:-1;chrX:270000-810000:-1;chrX:27440000-30960000:-1;chrX:30960001-31869999:0;chrX:31870000-32430000:1;chrX:32430001-32599999:0;chrX:32600000-38510000:-1;chrX:32610000-38510000:-1;chrX:3680001-3969999:0;chrX:38510001-40189999:0;chrX:3970000-6500000:-1;chrX:40190000-42790000:-1;chrX:40570000-42790000:-1;chrX:42790001-43479999:0;chrX:43480000-45230000:1;chrX:43590000-44170000:1;chrX:44640000-45230000:1;chrX:45230001-51699999:0;chrX:51700000-52110000:-1;chrX:52110001-53119999:0;chrX:53120000-54090000:1;chrX:54090001-54519999:0;chrX:54520000-57320000:-1;chrX:57320001-67859999:0;chrX:6500001-25239999:0;chrX:67860000-76140000:-1;chrX:69960000-71000000:-1;chrX:76140001-77339999:0;chrX:77340000-82140000:1;chrX:810001-829999:0;chrX:82140001-83239999:0;chrX:830000-940000:-1;chrX:83240000-85170000:1;chrX:83320000-85170000:1;chrX:85170001-86689999:0;chrX:86690000-93490000:1;chrX:93490001-93509999:0;chrX:93510000-97890000:-1;chrX:940001-1289999:0;chrX:97890001-100129999:0;chrY:0-57772954:0 Section of Breast Oncology, Division of Oncology, Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation. NCBI 36/hg18 phs000611 Yes C1orf182,MLL3;ESR1,YAP1 CTDB0288 Methodology 25938371 Chen X, Gupta P, Wang J, Nakitandwe J, Roberts K, Dalton JD, Parker M, Patel S, Holmfeldt L, Payne D, Easton J, Ma J, Rusch M, Wu G, Patel A, Baker SJ, Dyer MA, Shurtleff S, Espy S, Pounds S, Downing JR, Ellison DW, Mullighan CG, Zhang J CONSERTING: integrating copy-number analysis with structural-variation detection Nature methods 2015 Jun 7,12 Glioblastoma Next Generation Sequencing Homo sapiens 06-0152-01A EGFR;CDK4;MDM2 Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), an algorithm for detecting somatic copy-number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation on the basis of changes in read depth and the detection of localized structural variations, with high accuracy and sensitivity. Analysis of 43 cancer genomes from both pediatric and adult patients revealed novel oncogenic CNAs, complex rearrangements and subclonal CNAs missed by alternative approaches. GRCh37/hg19 phs000340;phs000352;phs000218;phs000178 Yes NA CTDB0289 Methodology 25938371 Chen X, Gupta P, Wang J, Nakitandwe J, Roberts K, Dalton JD, Parker M, Patel S, Holmfeldt L, Payne D, Easton J, Ma J, Rusch M, Wu G, Patel A, Baker SJ, Dyer MA, Shurtleff S, Espy S, Pounds S, Downing JR, Ellison DW, Mullighan CG, Zhang J CONSERTING: integrating copy-number analysis with structural-variation detection Nature methods 2015 Jun 1,2 Glioblastoma Next Generation Sequencing Homo sapiens 06-0210-01A MDM4 Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), an algorithm for detecting somatic copy-number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation on the basis of changes in read depth and the detection of localized structural variations, with high accuracy and sensitivity. Analysis of 43 cancer genomes from both pediatric and adult patients revealed novel oncogenic CNAs, complex rearrangements and subclonal CNAs missed by alternative approaches. GRCh37/hg19 phs000340;phs000352;phs000218;phs000178 Yes NA CTDB0290 Methodology 25938371 Chen X, Gupta P, Wang J, Nakitandwe J, Roberts K, Dalton JD, Parker M, Patel S, Holmfeldt L, Payne D, Easton J, Ma J, Rusch M, Wu G, Patel A, Baker SJ, Dyer MA, Shurtleff S, Espy S, Pounds S, Downing JR, Ellison DW, Mullighan CG, Zhang J CONSERTING: integrating copy-number analysis with structural-variation detection Nature methods 2015 Jun 4,7 Glioblastoma Next Generation Sequencing Homo sapiens 06-0211-01A EGFR;PDGFRA Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), an algorithm for detecting somatic copy-number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation on the basis of changes in read depth and the detection of localized structural variations, with high accuracy and sensitivity. Analysis of 43 cancer genomes from both pediatric and adult patients revealed novel oncogenic CNAs, complex rearrangements and subclonal CNAs missed by alternative approaches. GRCh37/hg19 phs000340;phs000352;phs000218;phs000178 Yes NA CTDB0291 Methodology 25938371 Chen X, Gupta P, Wang J, Nakitandwe J, Roberts K, Dalton JD, Parker M, Patel S, Holmfeldt L, Payne D, Easton J, Ma J, Rusch M, Wu G, Patel A, Baker SJ, Dyer MA, Shurtleff S, Espy S, Pounds S, Downing JR, Ellison DW, Mullighan CG, Zhang J CONSERTING: integrating copy-number analysis with structural-variation detection Nature methods 2015 Jun 4,7 Glioblastoma Next Generation Sequencing Homo sapiens 06-0211-02A EGFR;PDGFRA Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), an algorithm for detecting somatic copy-number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation on the basis of changes in read depth and the detection of localized structural variations, with high accuracy and sensitivity. Analysis of 43 cancer genomes from both pediatric and adult patients revealed novel oncogenic CNAs, complex rearrangements and subclonal CNAs missed by alternative approaches. GRCh37/hg19 phs000340;phs000352;phs000218;phs000178 Yes NA CTDB0292 Methodology 25938371 Chen X, Gupta P, Wang J, Nakitandwe J, Roberts K, Dalton JD, Parker M, Patel S, Holmfeldt L, Payne D, Easton J, Ma J, Rusch M, Wu G, Patel A, Baker SJ, Dyer MA, Shurtleff S, Espy S, Pounds S, Downing JR, Ellison DW, Mullighan CG, Zhang J CONSERTING: integrating copy-number analysis with structural-variation detection Nature methods 2015 Jun 12 Glioblastoma Next Generation Sequencing Homo sapiens 06-0648-01A CAND1;MDM2;CPM Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), an algorithm for detecting somatic copy-number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation on the basis of changes in read depth and the detection of localized structural variations, with high accuracy and sensitivity. Analysis of 43 cancer genomes from both pediatric and adult patients revealed novel oncogenic CNAs, complex rearrangements and subclonal CNAs missed by alternative approaches. GRCh37/hg19 phs000340;phs000352;phs000218;phs000178 Yes NA CTDB0293 Methodology 25938371 Chen X, Gupta P, Wang J, Nakitandwe J, Roberts K, Dalton JD, Parker M, Patel S, Holmfeldt L, Payne D, Easton J, Ma J, Rusch M, Wu G, Patel A, Baker SJ, Dyer MA, Shurtleff S, Espy S, Pounds S, Downing JR, Ellison DW, Mullighan CG, Zhang J CONSERTING: integrating copy-number analysis with structural-variation detection Nature methods 2015 Jun 7 Glioblastoma Next Generation Sequencing Homo sapiens 14-1402-01A EGFR Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), an algorithm for detecting somatic copy-number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation on the basis of changes in read depth and the detection of localized structural variations, with high accuracy and sensitivity. Analysis of 43 cancer genomes from both pediatric and adult patients revealed novel oncogenic CNAs, complex rearrangements and subclonal CNAs missed by alternative approaches. GRCh37/hg19 phs000340;phs000352;phs000218;phs000178 Yes NA CTDB0294 Methodology 25938371 Chen X, Gupta P, Wang J, Nakitandwe J, Roberts K, Dalton JD, Parker M, Patel S, Holmfeldt L, Payne D, Easton J, Ma J, Rusch M, Wu G, Patel A, Baker SJ, Dyer MA, Shurtleff S, Espy S, Pounds S, Downing JR, Ellison DW, Mullighan CG, Zhang J CONSERTING: integrating copy-number analysis with structural-variation detection Nature methods 2015 Jun 7 Glioblastoma Next Generation Sequencing Homo sapiens 14-1402-02A EGFR Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), an algorithm for detecting somatic copy-number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation on the basis of changes in read depth and the detection of localized structural variations, with high accuracy and sensitivity. Analysis of 43 cancer genomes from both pediatric and adult patients revealed novel oncogenic CNAs, complex rearrangements and subclonal CNAs missed by alternative approaches. GRCh37/hg19 phs000340;phs000352;phs000218;phs000178 Yes NA CTDB0295 Methodology 25938371 Chen X, Gupta P, Wang J, Nakitandwe J, Roberts K, Dalton JD, Parker M, Patel S, Holmfeldt L, Payne D, Easton J, Ma J, Rusch M, Wu G, Patel A, Baker SJ, Dyer MA, Shurtleff S, Espy S, Pounds S, Downing JR, Ellison DW, Mullighan CG, Zhang J CONSERTING: integrating copy-number analysis with structural-variation detection Nature methods 2015 Jun 4,12 Glioblastoma Next Generation Sequencing Homo sapiens 19-5960-01A CDK4 Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), an algorithm for detecting somatic copy-number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation on the basis of changes in read depth and the detection of localized structural variations, with high accuracy and sensitivity. Analysis of 43 cancer genomes from both pediatric and adult patients revealed novel oncogenic CNAs, complex rearrangements and subclonal CNAs missed by alternative approaches. GRCh37/hg19 phs000340;phs000352;phs000218;phs000178 Yes NA CTDB0296 Methodology 25938371 Chen X, Gupta P, Wang J, Nakitandwe J, Roberts K, Dalton JD, Parker M, Patel S, Holmfeldt L, Payne D, Easton J, Ma J, Rusch M, Wu G, Patel A, Baker SJ, Dyer MA, Shurtleff S, Espy S, Pounds S, Downing JR, Ellison DW, Mullighan CG, Zhang J CONSERTING: integrating copy-number analysis with structural-variation detection Nature methods 2015 Jun 7 Glioblastoma Next Generation Sequencing Homo sapiens 27-1831-01A EGFR Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), an algorithm for detecting somatic copy-number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation on the basis of changes in read depth and the detection of localized structural variations, with high accuracy and sensitivity. Analysis of 43 cancer genomes from both pediatric and adult patients revealed novel oncogenic CNAs, complex rearrangements and subclonal CNAs missed by alternative approaches. GRCh37/hg19 phs000340;phs000352;phs000218;phs000178 Yes NA CTDB0300 Research 22267523 Jiang Z, Jhunjhunwala S, Liu J, Haverty PM, Kennemer MI, Guan Y, Lee W, Carnevali P, Stinson J, Johnson S, Diao J, Yeung S, Jubb A, Ye W, Wu TD, Kapadia SB, de Sauvage FJ, Gentleman RC, Stern HM, Seshagiri S, Pant KP, Modrusan Z, Ballinger DG, Zhang Z The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients Genome Research 2012 Apr 11 Hepatocellular carcinoma Next Generation Sequencing Homo sapiens H384 hs1:237459374-237459731,hs11:69326266-69326793;hs1:237803220-237803554,hs11:69030220-69030519;hs11:68174928-68175207,hs11:111576997-111577265;hs11:68263776-68263934,hs11:111568063-111568201;hs11:68834611-68835103,hs11:69063232-69063535;hs11:69455238-69455748,hs11:99220072-99220607;hs11:69462705-69463095,hs11:99264863-99265121;hs11:69463061-69463415,hs11:69520345-69520543;hs11:69463944-69464292,hs13:111314565-111314959;hs11:69488929-69489325,hs11:99528987-99529335;hs11:99100510-99100897,hsX:1907040-1907618;hs12:7177879-7178352,hs12:7299289-7299792;hs13:107169509-107169692,hs13:108423879-108424078;hs13:107183258-107183591,hs13:107213137-107213501;hs13:108210800-108211323,hs13:109282898-109283336 CCND1;CNTN5;FGF19;LRP5;MYEOV;ORAOV1;PPP6R3;SIK2;TPCN2; Department of Bioinformatics and Computational Biology, Genentech Inc, South San Francisco, California 94080, USA Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC). HBV integration into the host genome has been reported, but its scale, impact and contribution to HCC development is not clear. Here, we sequenced the tumor and nontumor genomes (>80X coverage) and transcriptomes of four HCC patients and identified 255 HBV integration sites. Increased sequencing to 240X coverage revealed a proportionally higher number of integration sites. Clonal expansion of HBV-integrated hepatocytes was found specifically in tumor samples. We observe a diverse collection of genomic perturbations near viral integration sites, including direct gene disruption, viral promoter-driven human transcription, viral-human transcript fusion, and DNA copy number alteration. Thus, we report the most comprehensive characterization of HBV integration in hepatocellular carcinoma patients. Such widespread random viral integration will likely increase carcinogenic opportunities in HBV-infected individuals. GRCh37/hg19 phs000384 Yes CCND1,CARS2;CCND1,CNTN5;CCND1,FGF19;LRP5,SIK2;ORAOV1,CNTN5;PPP6R3,SIK2;TPCN2,MYEOV CTDB0301 Research 23496902 Jiao X, Hooper SD, Djureinovic T, Larsson C, Warnberg F, Tellgren-Roth C, Botling J, Sjoblom T Gene rearrangements in hormone receptor negative breast cancers revealed by mate pair sequencing BMC Genomics 2013 Mar 1,2,3,7,8,11,15,16,17,20,21,X,Y Breast cancer Next Generation Sequencing Homo sapiens 118T SOLiD3 chr10:0-135374737:0;chr11:0-134452384:0;chr12:0-132349534:0;chr13:0-114142980:0;chr14:0-106368585:0;chr15:0-55004818:0;chr15:55004819-58879386:-1;chr15:58879387-100338915:0;chr16:0-88827254:0;chr17:0-78774742:0;chr18:0-76117153:0;chr19:0-63811651:0;chr1:0-63476667:0;chr1:195690043-195690469:1;chr1:195690470-230523907:0;chr1:230523908-230528509:-1;chr1:230528510-247249719:0;chr1:63476668-63482030:-1;chr1:63482031-195690042:0;chr20:0-36255835:0;chr20:36255836-36257151:1;chr20:36257152-62435964:0;chr21:0-25220500:0;chr21:25220501-31517907:-1;chr21:31517908-46944323:0;chr22:0-49691432:0;chr2:0-70513576:0;chr2:70513577-70517836:-1;chr2:70517837-242951149:0;chr3:0-108519519:0;chr3:108519520-108524650:-1;chr3:108524651-134804179:0;chr3:134804180-134808444:-1;chr3:134808445-199501827:0;chr4:0-191273063:0;chr5:0-180857866:0;chr6:0-170899992:0;chr7:0-158821424:0;chr8:0-92600482:0;chr8:131918874-131923624:-1;chr8:131923625-141235875:0;chr8:141235876-141237150:1;chr8:141237151-143351438:0;chr8:143351439-143352831:1;chr8:143352832-146274826:0;chr8:92600483-92611590:-1;chr8:92611591-131918873:0;chr9:0-140273252:0;chrX:0-135125055:0;chrX:135125056-135131089:-1;chrX:135131090-154913754:0;chrY:0-57772954:0 hs2:172601516-172601516,hs2:175539159-175539159;hs15:57988348-57988348,hs15:58249409-58249409;hs15:59317692-59317692,hs15:67919721-67919721;hs21:27096176-27096176,hs21:40613558-40613558;hs21:27644155-27644155,hs21:30032969-30032969;hs21:30027728-30027728,hs21:45978888-45978888;hs11:55961514-55961514,hs11:70335355-70335355;hs21:26319139-26319139,hs21:34978397-34978397;hs11:55962145-55962145,hs11:70334660-70334660;hs15:58018756-58018756,hs21:45973422-45973422;hs15:58619373-58619373,hs21:34837891-34837891;hs15:59163813-59163813,hs21:26902586-26902586;hs15:69536585-69536585,hs21:16947278-16947278;hs7:89920909-89920909,hs17:22927514-22927514;hs15:58070776-58070776,hs21:40545794-40545794;hs15:71192826-71192826,hs21:18664764-18664764;hs15:67813088-67813088,hs21:17096313-17096313;hs1:203406073-203406073,hs17:67941744-67941744;hs15:56785572-56785572,hs21:35493037-35493037;hs15:56819851-56819851,hs21:26290149-26290149;hs15:56825407-56825407,hs21:35138237-35138237;hs15:57924318-57924318,hs21:36836122-36836122;hs15:58970133-58970133,hs21:28088365-28088365;hs15:58983956-58983956,hs21:46011615-46011615;hs15:59145037-59145037,hs21:40791222-40791222;hs15:63964813-63964813,hs21:30497263-30497263;hs15:64142747-64142747,hs21:34848420-34848420;hs15:69312660-69312660,hs21:28871349-28871349;hs15:70901061-70901061,hs21:38513266-38513266;hs16:33846095-33846095,hs24:10617572-10617572 ADAM10;ADCY8;APP;C15orf50;CHN1;CLDN14;CLIC6;CRB1;DSCAM;DSTYK;GRIK1;KSR1;LOC344595;MAP1D;NEO1;PRSS7;RAB11A;RCAN1;RORA;RUNX1;SHANK2;TCF12;THSD4;TIAM1;TOPBP1;TRAPPC9;TSNARE1; Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, SE 751 85, Sweden BACKGROUND: Chromosomal rearrangements in the form of deletions, insertions, inversions and translocations are frequently observed in breast cancer genomes, and a subset of these rearrangements may play a crucial role in tumorigenesis. To identify novel somatic chromosomal rearrangements, we determined the genome structures of 15 hormone-receptor negative breast tumors by long-insert mate pair massively parallel sequencing. RESULTS: We identified and validated 40 somatic structural alterations, including the recurring fusion between genes DDX10 and SKA3 and translocations involving the EPHA5 gene. Other rearrangements were found to affect genes in pathways involved in epigenetic regulation, mitosis and signal transduction, underscoring their potential role in breast tumorigenesis. RNA interference-mediated suppression of five candidate genes (DDX10, SKA3, EPHA5, CLTC and TNIK) led to inhibition of breast cancer cell growth. Moreover, downregulation of DDX10 in breast cancer cells lead to an increased frequency of apoptotic nuclear morphology. CONCLUSIONS: Using whole genome mate pair sequencing and RNA interference assays, we have discovered a number of novel gene rearrangements in breast cancer genomes and identified DDX10, SKA3, EPHA5, CLTC and TNIK as potential cancer genes with impact on the growth and proliferation of breast cancer cells. NCBI 36/hg18 Yes ADAM10,APP;ADAM10,RUNX1;MEGF11,RCAN1;RORA,DSCAM CTDB0319 Research 23796897 Zheng S, Fu J, Vegesna R, Mao Y, Heathcock LE, Torres-Garcia W, Ezhilarasan R, Wang S, McKenna A, Chin L, Brennan CW, Yung WK, Weinstein JN, Aldape KD, Sulman EP, Chen K, Koul D, Verhaak RG A survey of intragenic breakpoints in glioblastoma identifies a distinct subset associated with poor survival Genes & Development 2013 Jul 12 Glioblastoma Next Generation Sequencing Homo sapiens TCGA-06-0129 hs12:32552893-32552893,hs12:40619357-40619357;hs12:6954966-6954966,hs12:95869847-95869847;hs12:51386593-hs12:48501148-48516550;hs6:3410422-3410422,hs6:47221257-47221257;hs12:69864310-69885431,hs12:57957222-57957222;hs12:56663345-56664102,hs12:6964565-6964565;hs12:53861077-53861077,hs12:100482873-100482873;hs12:27156169-27156169,hs12:103670988-103670988;hs6:33393680-33393680,hs6:44220782-44220782;hs12:81929201-82147752,hs12:63954442-63954442;hs12:40345059-40345059,hs12:110834257-110834257;hs6:34791125-34791125,hs12:91358103-91358103;hs12:105538650-105538650,hs12:71928895-71928895;hs12:132630210-132629150,hs12:113837515-113837515;hs6:37623476-37626021,hs6:43126555-43126555;hs4:140222985-140222985,hs9:113638002-113638002;hs12:69756687-69756687,hs12:132522227-132527849 ANAPC7;C12orf42;COQ10A;DPY19L2;EP400;EPYC;FGD4;FRS2;Gene_B;GNB3;KIAA1033;KIF5A;LGR5;LRRK2;METAP2;NOC4L;PCBP2;PFKM;PPFIA2;SDS;SLC11A2;SLC2A13;TM7SF3;UHRF1BP1L;USP5;YEATS4; Department of Bioinformatics and Computational Biology With the advent of high-throughput sequencing technologies, much progress has been made in the identification of somatic structural rearrangements in cancer genomes. However, characterization of the complex alterations and their associated mechanisms remains inadequate. Here, we report a comprehensive analysis of whole-genome sequencing and DNA copy number data sets from The Cancer Genome Atlas to relate chromosomal alterations to imbalances in DNA dosage and describe the landscape of intragenic breakpoints in glioblastoma multiforme (GBM). Gene length, guanine-cytosine (GC) content, and local presence of a copy number alteration were closely associated with breakpoint susceptibility. A dense pattern of repeated focal amplifications involving the murine double minute 2 (MDM2)/cyclin-dependent kinase 4 (CDK4) oncogenes and associated with poor survival was identified in 5% of GBMs. Gene fusions and rearrangements were detected concomitant within the breakpoint-enriched region. At the gene level, we noted recurrent breakpoints in genes such as apoptosis regulator FAF1. Structural alterations of the FAF1 gene disrupted expression and led to protein depletion. Restoration of the FAF1 protein in glioma cell lines significantly increased the FAS-mediated apoptosis response. Our study uncovered a previously underappreciated genomic mechanism of gene deregulation that can confer growth advantages on tumor cells and may generate cancer-specific vulnerabilities in subsets of GBM. NCBI 36/hg18 Yes COQ10A,USP5;FGD4,LRRK2;FRS2,KIF5A;GNB3,METAP2;KIAA1033,LGR5;NOC4L,SDS;PCBP2,UHRF1BP1L;PPFIA2,DPY19L2;SLC11A2,PFKM;SLC2A13,ANAPC7;TM7SF3,C12orf42;UHRF1BP1,EPYC;YEATS4,EP400 CTDB0322 Research 25079552 Collisson EA, Campbell JD, Brooks AN, Berger AH, Lee W, Chmielecki J, Beer DG, Cope L, Creighton CJ, Danilova L, Ding L, Getz G, Hammerman PS, Hayes DN, Hernandez B, Herman JG, Heymach JV, Jurisica I, Kucherlapati R, Kwiatkowski D, Ladanyi M, Robertson G, Schultz N, Shen R, Sinha R, Sougnez C, Tsao MS, Travis WD, Weinstein JN, Wigle DA, Wilkerson MD, Chu A, Cherniack AD, Hadjipanayis A, Rosenberg M, Weisenberger DJ, Laird PW, Radenbaugh A, Ma S, Stuart JM, Averett Byers L, Baylin SB, Govindan R, Meyerson M, Rosenberg M, Gabriel SB, Cibulskis K, Sougnez C, Kim J, Stewart C, Lichtenstein L, Lander ES, Lawrence MS, Getz, Kandoth C, Fulton R, Fulton LL, McLellan MD, Wilson RK, Ye K, Fronick CC, Maher CA, Miller CA, Wendl MC, Cabanski C, Ding L, Mardis E, Govindan R, Creighton CJ, Wheeler D, Balasundaram M, Butterfield YS, Carlsen R, Chu A, Chuah E, Dhalla N, Guin R, Hirst C, Lee D, Li HI, Mayo M, Moore RA, Mungall AJ, Schein JE, Sipahimalani P, Tam A, Varhol R, Robertson A, Wye N, Thiessen N, Holt RA, Jones SJ, Marra MA, Campbell JD, Brooks AN, Chmielecki J, Imielinski M, Onofrio RC, Hodis E, Zack T, Sougnez C, Helman E, Sekhar Pedamallu C, Mesirov J, Cherniack AD, Saksena G, Schumacher SE, Carter SL, Hernandez B, Garraway L, Beroukhim R, Gabriel SB, Getz G, Meyerson M, Hadjipanayis A, Lee S, Mahadeshwar HS, Pantazi A, Protopopov A, Ren X, Seth S, Song X, Tang J, Yang L, Zhang J, Chen PC, Parfenov M, Wei Xu A, Santoso N, Chin L, Park PJ, Kucherlapati R, Hoadley KA, Auman JT, Meng S, Shi Y, Buda E, Waring S, Veluvolu U, Tan D, Mieczkowski PA, Jones CD, Simons JV, Soloway MG, Bodenheimer T, Jefferys SR, Roach J, Hoyle AP, Wu J, Balu S, Singh D, Prins JF, Marron JS, Parker JS, Hayes DN, Perou CM, Liu J, Cope L, Danilova L, Weisenberger DJ, Maglinte DT, Lai PH, Bootwalla MS, Van Den Berg DJ, Triche T Jr, Baylin SB, Laird PW, Rosenberg M, Chin L, Zhang J, Cho J, DiCara D, Heiman D, Lin P, Mallard W, Voet D, Zhang H, Zou L, Noble MS, Lawrence MS, Saksena G, Gehlenborg N, Thorvaldsdottir H, Mesirov J, Nazaire MD, Robinson J, Getz G, Lee W, Aksoy BA, Ciriello G, Taylor BS, Dresdner G, Gao J, Gross B, Seshan VE, Ladanyi M, Reva B, Sinha R, Sumer SO, Weinhold N, Schultz N, Shen R, Sander C, Ng S, Ma S, Zhu J, Radenbaugh A, Stuart JM, Benz CC, Yau C, Haussler D, Spellman PT, Wilkerson MD, Parker JS, Hoadley KA, Kimes PK, Hayes DN, Perou CM, Broom BM, Wang J, Lu Y, Kwok Shing Ng P, Diao L, Averett Byers L, Liu W, Heymach JV, Amos CI, Weinstein JN, Akbani R, Mills GB, Curley E, Paulauskis J, Lau K, Morris S, Shelton T, Mallery D, Gardner J, Penny R, Saller C, Tarvin K, Richards WG, Cerfolio R, Bryant A, Raymond DP, Pennell NA, Farver C, Czerwinski C, Huelsenbeck-Dill L, Iacocca M, Petrelli N, Rabeno B, Brown J, Bauer T, Dolzhanskiy O, Potapova O, Rotin D, Voronina O, Nemirovich-Danchenko E, Fedosenko KV, Gal A, Behera M, Ramalingam SS, Sica G, Flieder D, Boyd J, Weaver J, Kohl B, Huy Quoc Thinh D, Sandusky G, Juhl H, Duhig E, Illei P, Gabrielson E, Shin J, Lee B, Rodgers K, Trusty D, Brock MV, Williamson C, Burks E, Rieger-Christ K, Holway A, Sullivan T, Wigle DA, Asiedu MK, Kosari F, Travis WD, Rekhtman N, Zakowski M, Rusch VW, Zippile P, Suh J, Pass H, Goparaju C, Owusu-Sarpong Y, Bartlett JM, Kodeeswaran S, Parfitt J, Sekhon H, Albert M, Eckman J, Myers JB, Cheney R, Morrison C, Gaudioso C, Borgia JA, Bonomi P, Pool M, Liptay MJ, Moiseenko F, Zaytseva I, Dienemann H, Meister M, Schnabel PA, Muley TR, Peifer M, Gomez-Fernandez C, Herbert L, Egea S, Huang M, Thorne LB, Boice L, Hill Salazar A, Funkhouser WK, Rathmell WK, Dhir R, Yousem SA, Dacic S, Schneider F, Siegfried JM, Hajek R, Watson MA, McDonald S, Meyers B, Clarke B, Yang IA, Fong KM, Hunter L, Windsor M, Bowman RV, Peters S, Letovanec I, Khan KZ, Jensen MA, Snyder EE, Srinivasan D, Kahn AB, Baboud J, Pot DA, Mills Shaw KR, Sheth M, Davidsen T, Demchok JA, Yang L, Wang Z, Tarnuzzer R, Zenklusen JC, Ozenberger BA, Sofia HJ, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS Comprehensive molecular profiling of lung adenocarcinoma Nature 2014 Jul 1 Non Small-cell lung cancer Next Generation Sequencing Homo sapiens TCGA-05-5715 Illumina HiSeq2000 hs1:154938559-154938559,hs1:174656755-174656755;hs9:22038088-22038088,hs9:32410826-32410826;hs20:32851674-32851674,hs20:34367049-34367049;hs1:110884862-110884862,hs1:111688869-111688869;hs1:160175959-160175959,hs1:201254023-201254023 CEPT1;PEA15;PKP1;RABGAP1L;RBM15;SHC1; University of CaliforniaSan Francisco, San Francisco,California94158,USA Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis. GRCh37/hg19 Yes PEA15,PKP1;RBM15,CEPT1;SHC1,RABGAP1L CTDB0323 Research 25079552 Collisson EA, Campbell JD, Brooks AN, Berger AH, Lee W, Chmielecki J, Beer DG, Cope L, Creighton CJ, Danilova L, Ding L, Getz G, Hammerman PS, Hayes DN, Hernandez B, Herman JG, Heymach JV, Jurisica I, Kucherlapati R, Kwiatkowski D, Ladanyi M, Robertson G, Schultz N, Shen R, Sinha R, Sougnez C, Tsao MS, Travis WD, Weinstein JN, Wigle DA, Wilkerson MD, Chu A, Cherniack AD, Hadjipanayis A, Rosenberg M, Weisenberger DJ, Laird PW, Radenbaugh A, Ma S, Stuart JM, Averett Byers L, Baylin SB, Govindan R, Meyerson M, Rosenberg M, Gabriel SB, Cibulskis K, Sougnez C, Kim J, Stewart C, Lichtenstein L, Lander ES, Lawrence MS, Getz, Kandoth C, Fulton R, Fulton LL, McLellan MD, Wilson RK, Ye K, Fronick CC, Maher CA, Miller CA, Wendl MC, Cabanski C, Ding L, Mardis E, Govindan R, Creighton CJ, Wheeler D, Balasundaram M, Butterfield YS, Carlsen R, Chu A, Chuah E, Dhalla N, Guin R, Hirst C, Lee D, Li HI, Mayo M, Moore RA, Mungall AJ, Schein JE, Sipahimalani P, Tam A, Varhol R, Robertson A, Wye N, Thiessen N, Holt RA, Jones SJ, Marra MA, Campbell JD, Brooks AN, Chmielecki J, Imielinski M, Onofrio RC, Hodis E, Zack T, Sougnez C, Helman E, Sekhar Pedamallu C, Mesirov J, Cherniack AD, Saksena G, Schumacher SE, Carter SL, Hernandez B, Garraway L, Beroukhim R, Gabriel SB, Getz G, Meyerson M, Hadjipanayis A, Lee S, Mahadeshwar HS, Pantazi A, Protopopov A, Ren X, Seth S, Song X, Tang J, Yang L, Zhang J, Chen PC, Parfenov M, Wei Xu A, Santoso N, Chin L, Park PJ, Kucherlapati R, Hoadley KA, Auman JT, Meng S, Shi Y, Buda E, Waring S, Veluvolu U, Tan D, Mieczkowski PA, Jones CD, Simons JV, Soloway MG, Bodenheimer T, Jefferys SR, Roach J, Hoyle AP, Wu J, Balu S, Singh D, Prins JF, Marron JS, Parker JS, Hayes DN, Perou CM, Liu J, Cope L, Danilova L, Weisenberger DJ, Maglinte DT, Lai PH, Bootwalla MS, Van Den Berg DJ, Triche T Jr, Baylin SB, Laird PW, Rosenberg M, Chin L, Zhang J, Cho J, DiCara D, Heiman D, Lin P, Mallard W, Voet D, Zhang H, Zou L, Noble MS, Lawrence MS, Saksena G, Gehlenborg N, Thorvaldsdottir H, Mesirov J, Nazaire MD, Robinson J, Getz G, Lee W, Aksoy BA, Ciriello G, Taylor BS, Dresdner G, Gao J, Gross B, Seshan VE, Ladanyi M, Reva B, Sinha R, Sumer SO, Weinhold N, Schultz N, Shen R, Sander C, Ng S, Ma S, Zhu J, Radenbaugh A, Stuart JM, Benz CC, Yau C, Haussler D, Spellman PT, Wilkerson MD, Parker JS, Hoadley KA, Kimes PK, Hayes DN, Perou CM, Broom BM, Wang J, Lu Y, Kwok Shing Ng P, Diao L, Averett Byers L, Liu W, Heymach JV, Amos CI, Weinstein JN, Akbani R, Mills GB, Curley E, Paulauskis J, Lau K, Morris S, Shelton T, Mallery D, Gardner J, Penny R, Saller C, Tarvin K, Richards WG, Cerfolio R, Bryant A, Raymond DP, Pennell NA, Farver C, Czerwinski C, Huelsenbeck-Dill L, Iacocca M, Petrelli N, Rabeno B, Brown J, Bauer T, Dolzhanskiy O, Potapova O, Rotin D, Voronina O, Nemirovich-Danchenko E, Fedosenko KV, Gal A, Behera M, Ramalingam SS, Sica G, Flieder D, Boyd J, Weaver J, Kohl B, Huy Quoc Thinh D, Sandusky G, Juhl H, Duhig E, Illei P, Gabrielson E, Shin J, Lee B, Rodgers K, Trusty D, Brock MV, Williamson C, Burks E, Rieger-Christ K, Holway A, Sullivan T, Wigle DA, Asiedu MK, Kosari F, Travis WD, Rekhtman N, Zakowski M, Rusch VW, Zippile P, Suh J, Pass H, Goparaju C, Owusu-Sarpong Y, Bartlett JM, Kodeeswaran S, Parfitt J, Sekhon H, Albert M, Eckman J, Myers JB, Cheney R, Morrison C, Gaudioso C, Borgia JA, Bonomi P, Pool M, Liptay MJ, Moiseenko F, Zaytseva I, Dienemann H, Meister M, Schnabel PA, Muley TR, Peifer M, Gomez-Fernandez C, Herbert L, Egea S, Huang M, Thorne LB, Boice L, Hill Salazar A, Funkhouser WK, Rathmell WK, Dhir R, Yousem SA, Dacic S, Schneider F, Siegfried JM, Hajek R, Watson MA, McDonald S, Meyers B, Clarke B, Yang IA, Fong KM, Hunter L, Windsor M, Bowman RV, Peters S, Letovanec I, Khan KZ, Jensen MA, Snyder EE, Srinivasan D, Kahn AB, Baboud J, Pot DA, Mills Shaw KR, Sheth M, Davidsen T, Demchok JA, Yang L, Wang Z, Tarnuzzer R, Zenklusen JC, Ozenberger BA, Sofia HJ, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS Comprehensive molecular profiling of lung adenocarcinoma Nature 2014 Jul 1 Non Small-cell lung cancer Next Generation Sequencing Homo sapiens TCGA-50-5932 Illumina HiSeq2000 hs1:147129126-147129126,hs1:157775887-157775887;hs12:26133210-26133210,hs12:29769974-29769974;hs2:73751972-73751972,hs19:43017249-43017249;hs12:49216189-49216189,hs12:49334831-49334831 ACP6;FCRL1; University of CaliforniaSan Francisco, San Francisco,California94158,USA Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis. GRCh37/hg19 Yes ACP6,FCRL1 CTDB0324 Research 25079552 Collisson EA, Campbell JD, Brooks AN, Berger AH, Lee W, Chmielecki J, Beer DG, Cope L, Creighton CJ, Danilova L, Ding L, Getz G, Hammerman PS, Hayes DN, Hernandez B, Herman JG, Heymach JV, Jurisica I, Kucherlapati R, Kwiatkowski D, Ladanyi M, Robertson G, Schultz N, Shen R, Sinha R, Sougnez C, Tsao MS, Travis WD, Weinstein JN, Wigle DA, Wilkerson MD, Chu A, Cherniack AD, Hadjipanayis A, Rosenberg M, Weisenberger DJ, Laird PW, Radenbaugh A, Ma S, Stuart JM, Averett Byers L, Baylin SB, Govindan R, Meyerson M, Rosenberg M, Gabriel SB, Cibulskis K, Sougnez C, Kim J, Stewart C, Lichtenstein L, Lander ES, Lawrence MS, Getz, Kandoth C, Fulton R, Fulton LL, McLellan MD, Wilson RK, Ye K, Fronick CC, Maher CA, Miller CA, Wendl MC, Cabanski C, Ding L, Mardis E, Govindan R, Creighton CJ, Wheeler D, Balasundaram M, Butterfield YS, Carlsen R, Chu A, Chuah E, Dhalla N, Guin R, Hirst C, Lee D, Li HI, Mayo M, Moore RA, Mungall AJ, Schein JE, Sipahimalani P, Tam A, Varhol R, Robertson A, Wye N, Thiessen N, Holt RA, Jones SJ, Marra MA, Campbell JD, Brooks AN, Chmielecki J, Imielinski M, Onofrio RC, Hodis E, Zack T, Sougnez C, Helman E, Sekhar Pedamallu C, Mesirov J, Cherniack AD, Saksena G, Schumacher SE, Carter SL, Hernandez B, Garraway L, Beroukhim R, Gabriel SB, Getz G, Meyerson M, Hadjipanayis A, Lee S, Mahadeshwar HS, Pantazi A, Protopopov A, Ren X, Seth S, Song X, Tang J, Yang L, Zhang J, Chen PC, Parfenov M, Wei Xu A, Santoso N, Chin L, Park PJ, Kucherlapati R, Hoadley KA, Auman JT, Meng S, Shi Y, Buda E, Waring S, Veluvolu U, Tan D, Mieczkowski PA, Jones CD, Simons JV, Soloway MG, Bodenheimer T, Jefferys SR, Roach J, Hoyle AP, Wu J, Balu S, Singh D, Prins JF, Marron JS, Parker JS, Hayes DN, Perou CM, Liu J, Cope L, Danilova L, Weisenberger DJ, Maglinte DT, Lai PH, Bootwalla MS, Van Den Berg DJ, Triche T Jr, Baylin SB, Laird PW, Rosenberg M, Chin L, Zhang J, Cho J, DiCara D, Heiman D, Lin P, Mallard W, Voet D, Zhang H, Zou L, Noble MS, Lawrence MS, Saksena G, Gehlenborg N, Thorvaldsdottir H, Mesirov J, Nazaire MD, Robinson J, Getz G, Lee W, Aksoy BA, Ciriello G, Taylor BS, Dresdner G, Gao J, Gross B, Seshan VE, Ladanyi M, Reva B, Sinha R, Sumer SO, Weinhold N, Schultz N, Shen R, Sander C, Ng S, Ma S, Zhu J, Radenbaugh A, Stuart JM, Benz CC, Yau C, Haussler D, Spellman PT, Wilkerson MD, Parker JS, Hoadley KA, Kimes PK, Hayes DN, Perou CM, Broom BM, Wang J, Lu Y, Kwok Shing Ng P, Diao L, Averett Byers L, Liu W, Heymach JV, Amos CI, Weinstein JN, Akbani R, Mills GB, Curley E, Paulauskis J, Lau K, Morris S, Shelton T, Mallery D, Gardner J, Penny R, Saller C, Tarvin K, Richards WG, Cerfolio R, Bryant A, Raymond DP, Pennell NA, Farver C, Czerwinski C, Huelsenbeck-Dill L, Iacocca M, Petrelli N, Rabeno B, Brown J, Bauer T, Dolzhanskiy O, Potapova O, Rotin D, Voronina O, Nemirovich-Danchenko E, Fedosenko KV, Gal A, Behera M, Ramalingam SS, Sica G, Flieder D, Boyd J, Weaver J, Kohl B, Huy Quoc Thinh D, Sandusky G, Juhl H, Duhig E, Illei P, Gabrielson E, Shin J, Lee B, Rodgers K, Trusty D, Brock MV, Williamson C, Burks E, Rieger-Christ K, Holway A, Sullivan T, Wigle DA, Asiedu MK, Kosari F, Travis WD, Rekhtman N, Zakowski M, Rusch VW, Zippile P, Suh J, Pass H, Goparaju C, Owusu-Sarpong Y, Bartlett JM, Kodeeswaran S, Parfitt J, Sekhon H, Albert M, Eckman J, Myers JB, Cheney R, Morrison C, Gaudioso C, Borgia JA, Bonomi P, Pool M, Liptay MJ, Moiseenko F, Zaytseva I, Dienemann H, Meister M, Schnabel PA, Muley TR, Peifer M, Gomez-Fernandez C, Herbert L, Egea S, Huang M, Thorne LB, Boice L, Hill Salazar A, Funkhouser WK, Rathmell WK, Dhir R, Yousem SA, Dacic S, Schneider F, Siegfried JM, Hajek R, Watson MA, McDonald S, Meyers B, Clarke B, Yang IA, Fong KM, Hunter L, Windsor M, Bowman RV, Peters S, Letovanec I, Khan KZ, Jensen MA, Snyder EE, Srinivasan D, Kahn AB, Baboud J, Pot DA, Mills Shaw KR, Sheth M, Davidsen T, Demchok JA, Yang L, Wang Z, Tarnuzzer R, Zenklusen JC, Ozenberger BA, Sofia HJ, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS Comprehensive molecular profiling of lung adenocarcinoma Nature 2014 Jul 3 Non Small-cell lung cancer Next Generation Sequencing Homo sapiens TCGA-67-3771 Illumina HiSeq2000 University of CaliforniaSan Francisco, San Francisco,California94158,USA Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis. GRCh37/hg19 Yes NA CTDB0325 Research 25079552 Collisson EA, Campbell JD, Brooks AN, Berger AH, Lee W, Chmielecki J, Beer DG, Cope L, Creighton CJ, Danilova L, Ding L, Getz G, Hammerman PS, Hayes DN, Hernandez B, Herman JG, Heymach JV, Jurisica I, Kucherlapati R, Kwiatkowski D, Ladanyi M, Robertson G, Schultz N, Shen R, Sinha R, Sougnez C, Tsao MS, Travis WD, Weinstein JN, Wigle DA, Wilkerson MD, Chu A, Cherniack AD, Hadjipanayis A, Rosenberg M, Weisenberger DJ, Laird PW, Radenbaugh A, Ma S, Stuart JM, Averett Byers L, Baylin SB, Govindan R, Meyerson M, Rosenberg M, Gabriel SB, Cibulskis K, Sougnez C, Kim J, Stewart C, Lichtenstein L, Lander ES, Lawrence MS, Getz, Kandoth C, Fulton R, Fulton LL, McLellan MD, Wilson RK, Ye K, Fronick CC, Maher CA, Miller CA, Wendl MC, Cabanski C, Ding L, Mardis E, Govindan R, Creighton CJ, Wheeler D, Balasundaram M, Butterfield YS, Carlsen R, Chu A, Chuah E, Dhalla N, Guin R, Hirst C, Lee D, Li HI, Mayo M, Moore RA, Mungall AJ, Schein JE, Sipahimalani P, Tam A, Varhol R, Robertson A, Wye N, Thiessen N, Holt RA, Jones SJ, Marra MA, Campbell JD, Brooks AN, Chmielecki J, Imielinski M, Onofrio RC, Hodis E, Zack T, Sougnez C, Helman E, Sekhar Pedamallu C, Mesirov J, Cherniack AD, Saksena G, Schumacher SE, Carter SL, Hernandez B, Garraway L, Beroukhim R, Gabriel SB, Getz G, Meyerson M, Hadjipanayis A, Lee S, Mahadeshwar HS, Pantazi A, Protopopov A, Ren X, Seth S, Song X, Tang J, Yang L, Zhang J, Chen PC, Parfenov M, Wei Xu A, Santoso N, Chin L, Park PJ, Kucherlapati R, Hoadley KA, Auman JT, Meng S, Shi Y, Buda E, Waring S, Veluvolu U, Tan D, Mieczkowski PA, Jones CD, Simons JV, Soloway MG, Bodenheimer T, Jefferys SR, Roach J, Hoyle AP, Wu J, Balu S, Singh D, Prins JF, Marron JS, Parker JS, Hayes DN, Perou CM, Liu J, Cope L, Danilova L, Weisenberger DJ, Maglinte DT, Lai PH, Bootwalla MS, Van Den Berg DJ, Triche T Jr, Baylin SB, Laird PW, Rosenberg M, Chin L, Zhang J, Cho J, DiCara D, Heiman D, Lin P, Mallard W, Voet D, Zhang H, Zou L, Noble MS, Lawrence MS, Saksena G, Gehlenborg N, Thorvaldsdottir H, Mesirov J, Nazaire MD, Robinson J, Getz G, Lee W, Aksoy BA, Ciriello G, Taylor BS, Dresdner G, Gao J, Gross B, Seshan VE, Ladanyi M, Reva B, Sinha R, Sumer SO, Weinhold N, Schultz N, Shen R, Sander C, Ng S, Ma S, Zhu J, Radenbaugh A, Stuart JM, Benz CC, Yau C, Haussler D, Spellman PT, Wilkerson MD, Parker JS, Hoadley KA, Kimes PK, Hayes DN, Perou CM, Broom BM, Wang J, Lu Y, Kwok Shing Ng P, Diao L, Averett Byers L, Liu W, Heymach JV, Amos CI, Weinstein JN, Akbani R, Mills GB, Curley E, Paulauskis J, Lau K, Morris S, Shelton T, Mallery D, Gardner J, Penny R, Saller C, Tarvin K, Richards WG, Cerfolio R, Bryant A, Raymond DP, Pennell NA, Farver C, Czerwinski C, Huelsenbeck-Dill L, Iacocca M, Petrelli N, Rabeno B, Brown J, Bauer T, Dolzhanskiy O, Potapova O, Rotin D, Voronina O, Nemirovich-Danchenko E, Fedosenko KV, Gal A, Behera M, Ramalingam SS, Sica G, Flieder D, Boyd J, Weaver J, Kohl B, Huy Quoc Thinh D, Sandusky G, Juhl H, Duhig E, Illei P, Gabrielson E, Shin J, Lee B, Rodgers K, Trusty D, Brock MV, Williamson C, Burks E, Rieger-Christ K, Holway A, Sullivan T, Wigle DA, Asiedu MK, Kosari F, Travis WD, Rekhtman N, Zakowski M, Rusch VW, Zippile P, Suh J, Pass H, Goparaju C, Owusu-Sarpong Y, Bartlett JM, Kodeeswaran S, Parfitt J, Sekhon H, Albert M, Eckman J, Myers JB, Cheney R, Morrison C, Gaudioso C, Borgia JA, Bonomi P, Pool M, Liptay MJ, Moiseenko F, Zaytseva I, Dienemann H, Meister M, Schnabel PA, Muley TR, Peifer M, Gomez-Fernandez C, Herbert L, Egea S, Huang M, Thorne LB, Boice L, Hill Salazar A, Funkhouser WK, Rathmell WK, Dhir R, Yousem SA, Dacic S, Schneider F, Siegfried JM, Hajek R, Watson MA, McDonald S, Meyers B, Clarke B, Yang IA, Fong KM, Hunter L, Windsor M, Bowman RV, Peters S, Letovanec I, Khan KZ, Jensen MA, Snyder EE, Srinivasan D, Kahn AB, Baboud J, Pot DA, Mills Shaw KR, Sheth M, Davidsen T, Demchok JA, Yang L, Wang Z, Tarnuzzer R, Zenklusen JC, Ozenberger BA, Sofia HJ, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS Comprehensive molecular profiling of lung adenocarcinoma Nature 2014 Jul 19 Non Small-cell lung cancer Next Generation Sequencing Homo sapiens TCGA-49-4488 Illumina HiSeq2000 hs19:34171134-34171134,hs19:54941891-54941891;hs3:183967046-183967046,hs3:183967499-183967499;hs16:337134-337134,hs16:337641-337641;hs17:79281429-79281429,hs17:79496259-79496259;hs22:18958602-18958602,hs22:20254952-20254952;hs5:176057323-176057323,hs5:176057832-176057832;hs15:27471932-27471932,hs19:54971210-54971210;hs1:40633928-40633928,hsX:73229417-73229417 CHST8; University of CaliforniaSan Francisco, San Francisco,California94158,USA Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis. GRCh37/hg19 Yes CHST8,TTYH1 CTDB0326 Research 25079552 Collisson EA, Campbell JD, Brooks AN, Berger AH, Lee W, Chmielecki J, Beer DG, Cope L, Creighton CJ, Danilova L, Ding L, Getz G, Hammerman PS, Hayes DN, Hernandez B, Herman JG, Heymach JV, Jurisica I, Kucherlapati R, Kwiatkowski D, Ladanyi M, Robertson G, Schultz N, Shen R, Sinha R, Sougnez C, Tsao MS, Travis WD, Weinstein JN, Wigle DA, Wilkerson MD, Chu A, Cherniack AD, Hadjipanayis A, Rosenberg M, Weisenberger DJ, Laird PW, Radenbaugh A, Ma S, Stuart JM, Averett Byers L, Baylin SB, Govindan R, Meyerson M, Rosenberg M, Gabriel SB, Cibulskis K, Sougnez C, Kim J, Stewart C, Lichtenstein L, Lander ES, Lawrence MS, Getz, Kandoth C, Fulton R, Fulton LL, McLellan MD, Wilson RK, Ye K, Fronick CC, Maher CA, Miller CA, Wendl MC, Cabanski C, Ding L, Mardis E, Govindan R, Creighton CJ, Wheeler D, Balasundaram M, Butterfield YS, Carlsen R, Chu A, Chuah E, Dhalla N, Guin R, Hirst C, Lee D, Li HI, Mayo M, Moore RA, Mungall AJ, Schein JE, Sipahimalani P, Tam A, Varhol R, Robertson A, Wye N, Thiessen N, Holt RA, Jones SJ, Marra MA, Campbell JD, Brooks AN, Chmielecki J, Imielinski M, Onofrio RC, Hodis E, Zack T, Sougnez C, Helman E, Sekhar Pedamallu C, Mesirov J, Cherniack AD, Saksena G, Schumacher SE, Carter SL, Hernandez B, Garraway L, Beroukhim R, Gabriel SB, Getz G, Meyerson M, Hadjipanayis A, Lee S, Mahadeshwar HS, Pantazi A, Protopopov A, Ren X, Seth S, Song X, Tang J, Yang L, Zhang J, Chen PC, Parfenov M, Wei Xu A, Santoso N, Chin L, Park PJ, Kucherlapati R, Hoadley KA, Auman JT, Meng S, Shi Y, Buda E, Waring S, Veluvolu U, Tan D, Mieczkowski PA, Jones CD, Simons JV, Soloway MG, Bodenheimer T, Jefferys SR, Roach J, Hoyle AP, Wu J, Balu S, Singh D, Prins JF, Marron JS, Parker JS, Hayes DN, Perou CM, Liu J, Cope L, Danilova L, Weisenberger DJ, Maglinte DT, Lai PH, Bootwalla MS, Van Den Berg DJ, Triche T Jr, Baylin SB, Laird PW, Rosenberg M, Chin L, Zhang J, Cho J, DiCara D, Heiman D, Lin P, Mallard W, Voet D, Zhang H, Zou L, Noble MS, Lawrence MS, Saksena G, Gehlenborg N, Thorvaldsdottir H, Mesirov J, Nazaire MD, Robinson J, Getz G, Lee W, Aksoy BA, Ciriello G, Taylor BS, Dresdner G, Gao J, Gross B, Seshan VE, Ladanyi M, Reva B, Sinha R, Sumer SO, Weinhold N, Schultz N, Shen R, Sander C, Ng S, Ma S, Zhu J, Radenbaugh A, Stuart JM, Benz CC, Yau C, Haussler D, Spellman PT, Wilkerson MD, Parker JS, Hoadley KA, Kimes PK, Hayes DN, Perou CM, Broom BM, Wang J, Lu Y, Kwok Shing Ng P, Diao L, Averett Byers L, Liu W, Heymach JV, Amos CI, Weinstein JN, Akbani R, Mills GB, Curley E, Paulauskis J, Lau K, Morris S, Shelton T, Mallery D, Gardner J, Penny R, Saller C, Tarvin K, Richards WG, Cerfolio R, Bryant A, Raymond DP, Pennell NA, Farver C, Czerwinski C, Huelsenbeck-Dill L, Iacocca M, Petrelli N, Rabeno B, Brown J, Bauer T, Dolzhanskiy O, Potapova O, Rotin D, Voronina O, Nemirovich-Danchenko E, Fedosenko KV, Gal A, Behera M, Ramalingam SS, Sica G, Flieder D, Boyd J, Weaver J, Kohl B, Huy Quoc Thinh D, Sandusky G, Juhl H, Duhig E, Illei P, Gabrielson E, Shin J, Lee B, Rodgers K, Trusty D, Brock MV, Williamson C, Burks E, Rieger-Christ K, Holway A, Sullivan T, Wigle DA, Asiedu MK, Kosari F, Travis WD, Rekhtman N, Zakowski M, Rusch VW, Zippile P, Suh J, Pass H, Goparaju C, Owusu-Sarpong Y, Bartlett JM, Kodeeswaran S, Parfitt J, Sekhon H, Albert M, Eckman J, Myers JB, Cheney R, Morrison C, Gaudioso C, Borgia JA, Bonomi P, Pool M, Liptay MJ, Moiseenko F, Zaytseva I, Dienemann H, Meister M, Schnabel PA, Muley TR, Peifer M, Gomez-Fernandez C, Herbert L, Egea S, Huang M, Thorne LB, Boice L, Hill Salazar A, Funkhouser WK, Rathmell WK, Dhir R, Yousem SA, Dacic S, Schneider F, Siegfried JM, Hajek R, Watson MA, McDonald S, Meyers B, Clarke B, Yang IA, Fong KM, Hunter L, Windsor M, Bowman RV, Peters S, Letovanec I, Khan KZ, Jensen MA, Snyder EE, Srinivasan D, Kahn AB, Baboud J, Pot DA, Mills Shaw KR, Sheth M, Davidsen T, Demchok JA, Yang L, Wang Z, Tarnuzzer R, Zenklusen JC, Ozenberger BA, Sofia HJ, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS Comprehensive molecular profiling of lung adenocarcinoma Nature 2014 Jul 20 Non Small-cell lung cancer Next Generation Sequencing Homo sapiens TCGA-75-5146 Illumina HiSeq2000 hs20:37003684-37003684,hs20:37606817-37606817;hs20:42193179-42193179,hs20:46220158-46220158 LBP;SGK2;DHX35;NCOA3; University of CaliforniaSan Francisco, San Francisco,California94158,USA Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis. GRCh37/hg19 Yes LBP,DHX35;SGK2,NCOA3 CTDB0327 Research 25079552 Collisson EA, Campbell JD, Brooks AN, Berger AH, Lee W, Chmielecki J, Beer DG, Cope L, Creighton CJ, Danilova L, Ding L, Getz G, Hammerman PS, Hayes DN, Hernandez B, Herman JG, Heymach JV, Jurisica I, Kucherlapati R, Kwiatkowski D, Ladanyi M, Robertson G, Schultz N, Shen R, Sinha R, Sougnez C, Tsao MS, Travis WD, Weinstein JN, Wigle DA, Wilkerson MD, Chu A, Cherniack AD, Hadjipanayis A, Rosenberg M, Weisenberger DJ, Laird PW, Radenbaugh A, Ma S, Stuart JM, Averett Byers L, Baylin SB, Govindan R, Meyerson M, Rosenberg M, Gabriel SB, Cibulskis K, Sougnez C, Kim J, Stewart C, Lichtenstein L, Lander ES, Lawrence MS, Getz, Kandoth C, Fulton R, Fulton LL, McLellan MD, Wilson RK, Ye K, Fronick CC, Maher CA, Miller CA, Wendl MC, Cabanski C, Ding L, Mardis E, Govindan R, Creighton CJ, Wheeler D, Balasundaram M, Butterfield YS, Carlsen R, Chu A, Chuah E, Dhalla N, Guin R, Hirst C, Lee D, Li HI, Mayo M, Moore RA, Mungall AJ, Schein JE, Sipahimalani P, Tam A, Varhol R, Robertson A, Wye N, Thiessen N, Holt RA, Jones SJ, Marra MA, Campbell JD, Brooks AN, Chmielecki J, Imielinski M, Onofrio RC, Hodis E, Zack T, Sougnez C, Helman E, Sekhar Pedamallu C, Mesirov J, Cherniack AD, Saksena G, Schumacher SE, Carter SL, Hernandez B, Garraway L, Beroukhim R, Gabriel SB, Getz G, Meyerson M, Hadjipanayis A, Lee S, Mahadeshwar HS, Pantazi A, Protopopov A, Ren X, Seth S, Song X, Tang J, Yang L, Zhang J, Chen PC, Parfenov M, Wei Xu A, Santoso N, Chin L, Park PJ, Kucherlapati R, Hoadley KA, Auman JT, Meng S, Shi Y, Buda E, Waring S, Veluvolu U, Tan D, Mieczkowski PA, Jones CD, Simons JV, Soloway MG, Bodenheimer T, Jefferys SR, Roach J, Hoyle AP, Wu J, Balu S, Singh D, Prins JF, Marron JS, Parker JS, Hayes DN, Perou CM, Liu J, Cope L, Danilova L, Weisenberger DJ, Maglinte DT, Lai PH, Bootwalla MS, Van Den Berg DJ, Triche T Jr, Baylin SB, Laird PW, Rosenberg M, Chin L, Zhang J, Cho J, DiCara D, Heiman D, Lin P, Mallard W, Voet D, Zhang H, Zou L, Noble MS, Lawrence MS, Saksena G, Gehlenborg N, Thorvaldsdottir H, Mesirov J, Nazaire MD, Robinson J, Getz G, Lee W, Aksoy BA, Ciriello G, Taylor BS, Dresdner G, Gao J, Gross B, Seshan VE, Ladanyi M, Reva B, Sinha R, Sumer SO, Weinhold N, Schultz N, Shen R, Sander C, Ng S, Ma S, Zhu J, Radenbaugh A, Stuart JM, Benz CC, Yau C, Haussler D, Spellman PT, Wilkerson MD, Parker JS, Hoadley KA, Kimes PK, Hayes DN, Perou CM, Broom BM, Wang J, Lu Y, Kwok Shing Ng P, Diao L, Averett Byers L, Liu W, Heymach JV, Amos CI, Weinstein JN, Akbani R, Mills GB, Curley E, Paulauskis J, Lau K, Morris S, Shelton T, Mallery D, Gardner J, Penny R, Saller C, Tarvin K, Richards WG, Cerfolio R, Bryant A, Raymond DP, Pennell NA, Farver C, Czerwinski C, Huelsenbeck-Dill L, Iacocca M, Petrelli N, Rabeno B, Brown J, Bauer T, Dolzhanskiy O, Potapova O, Rotin D, Voronina O, Nemirovich-Danchenko E, Fedosenko KV, Gal A, Behera M, Ramalingam SS, Sica G, Flieder D, Boyd J, Weaver J, Kohl B, Huy Quoc Thinh D, Sandusky G, Juhl H, Duhig E, Illei P, Gabrielson E, Shin J, Lee B, Rodgers K, Trusty D, Brock MV, Williamson C, Burks E, Rieger-Christ K, Holway A, Sullivan T, Wigle DA, Asiedu MK, Kosari F, Travis WD, Rekhtman N, Zakowski M, Rusch VW, Zippile P, Suh J, Pass H, Goparaju C, Owusu-Sarpong Y, Bartlett JM, Kodeeswaran S, Parfitt J, Sekhon H, Albert M, Eckman J, Myers JB, Cheney R, Morrison C, Gaudioso C, Borgia JA, Bonomi P, Pool M, Liptay MJ, Moiseenko F, Zaytseva I, Dienemann H, Meister M, Schnabel PA, Muley TR, Peifer M, Gomez-Fernandez C, Herbert L, Egea S, Huang M, Thorne LB, Boice L, Hill Salazar A, Funkhouser WK, Rathmell WK, Dhir R, Yousem SA, Dacic S, Schneider F, Siegfried JM, Hajek R, Watson MA, McDonald S, Meyers B, Clarke B, Yang IA, Fong KM, Hunter L, Windsor M, Bowman RV, Peters S, Letovanec I, Khan KZ, Jensen MA, Snyder EE, Srinivasan D, Kahn AB, Baboud J, Pot DA, Mills Shaw KR, Sheth M, Davidsen T, Demchok JA, Yang L, Wang Z, Tarnuzzer R, Zenklusen JC, Ozenberger BA, Sofia HJ, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS Comprehensive molecular profiling of lung adenocarcinoma Nature 2014 Jul 1,2,3,4,5,6,7,8,9,10,11,12,14,16,17,20,22 Non Small-cell lung cancer Next Generation Sequencing Homo sapiens TCGA-05-4422 Illumina HiSeq2000 hs1:161007168-161007168,hs1:161009255-161009255;hs1:156049319-156049319,hs1:156052448-156052448;hs1:154990699-154990699,hs1:154991513-154991513;hs1:154965365-154965365,hs1:154966421-154966421;hs2:103353077-103353077,hs2:103353554-103353554;hs2:201753339-201753339,hs2:201754297-201754297;hs2:88368320-88368320,hs10:1391209-1391209;hs3:51989997-51989997,hs3:51992691-51992691;hs3:127391515-127391515,hs3:127392399-127392399;hs3:52719331-52719331,hs3:52720165-52720165;hs3:9438808-9438808,hs3:9439548-9439548;hs3:45829795-45829795,hs3:135878615-135878615;hs3:142456234-142456234,hs8:126352258-126352258;hs3:48301781-48301781,hs8:97835494-97835494;hs4:159592226-159592226,hs4:159593516-159593516;hs4:38086202-38086202,hs9:114659622-114659622;hs5:17216875-17216875,hs5:17219098-17219098;hs5:43191913-43191913,hs5:43192395-43192395;hs6:30614332-30614332,hs6:30615447-30615447;hs6:170151151-170151151,hs6:170151981-170151981;hs6:41747251-41747251,hs6:41749859-41749859;hs6:160210358-160210358,hs6:160211341-160211341;hs6:90961006-90961006,hs8:99794696-99794696;hs7:93527147-93527147,hs7:147670389-147670389;hs7:102104835-102104835,hs7:102105579-102105579;hs8:89312455-89312455,hs8:124351930-124351930;hs8:70742683-70742683,hs8:124427162-124427162;hs8:133052468-133052468,hs8:136487430-136487430;hs8:119311455-119311455,hs8:133052468-133052468;hs8:131078448-131078448,hs14:102603255-102603255;hs10:38465547-38465547,hs10:129739835-129739835;hs10:88717373-88717373,hs10:88718937-88718937;hs11:63764678-63764678,hs11:63766671-63766671;hs12:124117996-124117996,hs12:124118881-124118881;hs12:58165400-58165400,hs12:58166447-58166447;hs16:90038817-90038817,hs16:90039486-90039486;hs16:67700346-67700346,hs16:67701307-67701307;hs16:84178105-84178105,hs16:84179473-84179473;hs17:74722148-74722148,hs17:74723192-74723192;hs17:17942214-17942214,hs17:17943112-17943112;hs20:62329265-62329265,hs20:62330803-62330803;hs20:62375143-62375143,hs20:62375980-62375980;hs22:24951444-24951444,hs22:24952108-24952108;hs22:29655456-29655456,hs22:29656535-29656535 ABTB1;ADARB2;AFG3L1;ALKBH4;ARFRP1;ASAP1;ATAD2;ATPAF2;BACH2;BASP1;C16orf48;C16orf86;C17orf39;C17orf95;C22orf13;C4orf46;C6orf136;CENPBD1;CNTNAP2;DCST2;EIF2B1;EMID1;ETFDH;F11R;FAM119B;FLAD1;FRS3;GNGT1;GNL3;GPR62;GTF2H3;HSDL1;HSP90AA1;JMJD6;KHDRBS3;LENEP;LMNA;LOC440944;LRRC50;LRWD1;MACROD1;METTL1;MEX3A;MFSD9;MGC42105;MMP16;MMRN2;MRPL18;MSL2;NIF3L1;NSMCE2;OC90;OTUB1;PBRM1;PCBP4;PGCP;PODXL2;PPIL3;PRICKLE4;PTPRE;RHBDD3;RTEL1;TNFRSF6B;SAMD12;SETD5;SLC2A4RG;SLC6A20;SLCO5A1;SMYD1;SNCG;SNRPD3;STK3;TBC1D1;TCP1;TMEM182;TRPC1;UGCG;USF1;ZBTB46;ZBTB7B;ZNF131;ZNF589; University of CaliforniaSan Francisco, San Francisco,California94158,USA Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis. GRCh37/hg19 Yes ALKBH4,LRWD1;ASAP1,HSP90AA1;ATPAF2,C17orf39;BACH2,STK3;C16orf48,C16orf86;C22orf13,SNRPD3;C4orf46,ETFDH;C6orf134,C6orf136;CENPBD1,AFG3L1;EIF2B1,GTF2H3;EMID1,RHBDD3;F11R,USF1;FLAD1,LENEP;FRS3,PRICKLE4;GNGT1,CNTNAP2;GPR62,PCBP4;HSDL1,LRRC50;JMJD6,C17orf95;LOC100129055,PTPRE;LOC285696,BASP1;LOC440944,SETD5;METTL1,FAM119B;MEX3A,LMNA;MFSD9,TMEM182;MMP16,ATAD2;MMRN2,SNCG;OC90,KHDRBS3;OTUB1,MACROD1;PBRM1,GNL3;PODXL2,ABTB1;PPIL3,NIF3L1;RTEL1;TNFRSF6B,ARFRP1;SAMD12,OC90;SLC2A4RG,ZBTB46;SLC6A20,MSL2;SLCO5A1,ATAD2;SMYD1,ADARB2;TBC1D1,UGCG;TCP1,MRPL18;TCTE3,C6orf70;TRPC1,NSMCE2;ZBTB7B,DCST2;ZNF131,MGC42105;ZNF589,PGCP CTDB0329 Research 24670920 Fernandez-Cuesta L, Peifer M, Lu X, Sun R, Ozretic L, Seidel D, Zander T, Leenders F, George J, Muller C, Dahmen I, Pinther B, Bosco G, Konrad K, Altmuller J, Nurnberg P, Achter V, Lang U, Schneider PM, Bogus M, Soltermann A, Brustugun OT, Helland A, Solberg S, Lund-Iversen M, Ansen S, Stoelben E, Wright GM, Russell P, Wainer Z, Solomon B, Field JK, Hyde R, Davies MP, Heukamp LC, Petersen I, Perner S, Lovly CM, Cappuzzo F, Travis WD, Wolf J, Vingron M, Brambilla E, Haas SA, Buettner R, Thomas RK Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids Nature Communications 2014 Mar 3,12,13 Pulmonary carcinoid Next Generation Sequencing Homo sapiens S00076 Illumina HiSeq2000 hs13:39540810-39541129,hs13:98628918-98634837;hs3:158072644-158262115,hs3:71630699-71630803;hs12:109490434-109495913,hs3:14239528-14239844;hs12:300116-304493,hs3:44490051-44492076;hs3:96706171-96706835,hs12:122243069-122244011;hs12:50571665-50575822,hs12:96679820-96683000;hs12:46123831-46125097,hs3:87299023-87302616;hs3:136581127-136647070,hs3:52156413-52159199;hs12:2906302-2913091,hs3:123550392-123550519;hs3:50471768-50513632,hs3:191047373-191047513;hs13:101707771-101712320,hs3:41268694-41268843;hs12:102517663-102517819,hs3:196678758-196678907;hs12:111057640-111066662,hs12:110002923-110011184;hs3:184684462-184711853,hs13:99908581-99908773;hs3:73651503-73673326,hs3:45707139-45714272;hs13:98086751-98087039,hs12:97303528-97306595;hs13:39917770-40175529,hs3:4725988-4726891;hs12:51818672-51818821,hs13:109817246-109817341;hs12:2102428-2113491,hs3:17447909-17448018;hs3:151597637-151598493,hs3:121544895-121547378;hs3:160783186-160783320,hs3:47956305-47956395;hs3:136471036-136471179,hs3:130744346-130744440 STOML3;1IPO5;RSRC1;1FOXP1;USP30;1LSM3;SLC6A12;1ZNF445;SETD1B;IEPHA6;CDK17;1LIMA1;ARID2;ICHMP2B;POC1A;1NCK1;FKBP4;1MYLK;CACNA2D2;1CCDC50;CTNNB1;1NALCN;C12orf48;1PIGZ;TCTN1;1MMAB;GPR18;1VPS8;PDZRN3;1LIMD1;NEDD1;1RAP2A;LHFP;1ITPR1;LOC100288040;1MYO16;TBC1D5;1DCP1B;SUCNR1;1IQCB1;PPM1L;1MAP4;STAG1;IASTE1; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50924 Cologne, Germany Pulmonary carcinoids are rare neuroendocrine tumours of the lung. The molecular alterations underlying the pathogenesis of these tumours have not been systematically studied so far. Here we perform gene copy number analysis (n=54), genome/exome (n=44) and transcriptome (n=69) sequencing of pulmonary carcinoids and observe frequent mutations in chromatin-remodelling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40 and 22.2% of the cases, respectively, with MEN1, PSIP1 and ARID1A being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine lung tumours, TP53 and RB1 mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumours but arise through independent cellular mechanisms. These data also suggest that inactivation of chromatin-remodelling genes is sufficient to drive transformation in pulmonary carcinoids. GRCh37/hg19 Yes ARID2,ICHMP2B;C12orf48,1PIGZ;CACNA2D2,1CCDC50;CDK17,1LIMA1;CTNNB1,1NALCN;FKBP4,1MYLK;GPR18,1VPS8;LHFP,1ITPR1;LOC100288040,1MYO16;NEDD1,1RAP2A;PDZRN3,1LIMD1;POC1A,1NCK1;PPM1L,1MAP4;RSRC1,1FOXP1;SETD1B,IEPHA6;SLC6A12,1ZNF445;STAG1,IASTE1;STOML3,1IPO5;SUCNR1,1IQCB1;TBC1D5,1DCP1B;TCTN1,1MMAB;USP30,1LSM3 CTDB0336 Research 25497101 van Heesch S, Simonis M, van Roosmalen MJ, Pillalamarri V, Brand H, Kuijk EW, de Luca KL, Lansu N, Braat AK, Menelaou A, Hao W, Korving J, Snijder S, van der Veken LT, Hochstenbach R, Knegt AC, Duran K, Renkens I, Alekozai N, Jager M, Vergult S, Menten B, de Bruijn E, Boymans S, Ippel E, van Binsbergen E, Talkowski ME, Lichtenbelt K, Cuppen E, Kloosterman WP Genomic and functional overlap between somatic and germline chromosomal rearrangements Cell Reports 2014 Dec 1,3,7,12 Congenital abnormality Next Generation Sequencing Homo sapiens patient 1 SOLiD V4 DPYD;FOXP1;ETV1;SNX13;TMEM106B;AHR;ARL4A; Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted. GRCh37/hg19 PRJEB5063;PRJEB3030 No DPYD,ETV1 CTDB0338 Research 24613930 Kelly LM, Barila G, Liu P, Evdokimova VN, Trivedi S, Panebianco F, Gandhi M, Carty SE, Hodak SP, Luo J, Dacic S, Yu YP, Nikiforova MN, Ferris RL, Altschuler DL, Nikiforov YE Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer Proceedings of the National Academy of Sciences of the United States of America 2014 Mar 2 Thyroid cancer Next Generation Sequencing Homo sapiens 11-14T Illumina HiSeq2000 STRN;ALK;KLHL29;MRPL33;BRE;BIRC6;LTDP1;LINC00486; Department of Pathology and Laboratory Medicine, Department of Pharmacology and Chemical Biology, Department of Otolaryngology, Department of Surgery, Division of Endocrine Surgery, and Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 Thyroid cancer is a common endocrine malignancy that encompasses well-differentiated as well as dedifferentiated cancer types. The latter tumors have high mortality and lack effective therapies. Using a paired-end RNA-sequencing approach, we report the discovery of rearrangements involving the anaplastic lymphoma kinase (ALK) gene in thyroid cancer. The most common of these involves a fusion between ALK and the striatin (STRN) gene, which is the result of a complex rearrangement involving the short arm of chromosome 2. STRN-ALK leads to constitutive activation of ALK kinase via dimerization mediated by the coiled-coil domain of STRN and to a kinase-dependent, thyroid-stimulating hormone-independent proliferation of thyroid cells. Moreover, expression of STRN-ALK transforms cells in vitro and induces tumor formation in nude mice. The kinase activity of STRN-ALK and the ALK-induced cell growth can be blocked by the ALK inhibitors crizotinib and TAE684. In addition to well-differentiated papillary cancer, STRN-ALK was found with a higher prevalence in poorly differentiated and anaplastic thyroid cancers, and it did not overlap with other known driver mutations in these tumors. Our data demonstrate that STRN-ALK fusion occurs in a subset of patients with highly aggressive types of thyroid cancer and provide initial evidence suggesting that it may represent a therapeutic target for these patients. GRCh37/hg19 Yes ALK,SRTN CTDB0339 Research 24613930 Kelly LM, Barila G, Liu P, Evdokimova VN, Trivedi S, Panebianco F, Gandhi M, Carty SE, Hodak SP, Luo J, Dacic S, Yu YP, Nikiforova MN, Ferris RL, Altschuler DL, Nikiforov YE Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer Proceedings of the National Academy of Sciences of the United States of America 2014 Mar 2 Thyroid cancer Next Generation Sequencing Homo sapiens 233323T Illumina HiSeq2000 STRN;ALK;KLHL29;MRPL33;BRE;BIRC6;LTDP1;LINC00486; Department of Pathology and Laboratory Medicine, Department of Pharmacology and Chemical Biology, Department of Otolaryngology, Department of Surgery, Division of Endocrine Surgery, and Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 Thyroid cancer is a common endocrine malignancy that encompasses well-differentiated as well as dedifferentiated cancer types. The latter tumors have high mortality and lack effective therapies. Using a paired-end RNA-sequencing approach, we report the discovery of rearrangements involving the anaplastic lymphoma kinase (ALK) gene in thyroid cancer. The most common of these involves a fusion between ALK and the striatin (STRN) gene, which is the result of a complex rearrangement involving the short arm of chromosome 2. STRN-ALK leads to constitutive activation of ALK kinase via dimerization mediated by the coiled-coil domain of STRN and to a kinase-dependent, thyroid-stimulating hormone-independent proliferation of thyroid cells. Moreover, expression of STRN-ALK transforms cells in vitro and induces tumor formation in nude mice. The kinase activity of STRN-ALK and the ALK-induced cell growth can be blocked by the ALK inhibitors crizotinib and TAE684. In addition to well-differentiated papillary cancer, STRN-ALK was found with a higher prevalence in poorly differentiated and anaplastic thyroid cancers, and it did not overlap with other known driver mutations in these tumors. Our data demonstrate that STRN-ALK fusion occurs in a subset of patients with highly aggressive types of thyroid cancer and provide initial evidence suggesting that it may represent a therapeutic target for these patients. GRCh37/hg19 Yes ALK,SRTN CTDB0340 Research 22622578 Berger MF, Hodis E, Heffernan TP, Deribe YL, Lawrence MS, Protopopov A, Ivanova E, Watson IR, Nickerson E, Ghosh P, Zhang H, Zeid R, Ren X, Cibulskis K, Sivachenko AY, Wagle N, Sucker A, Sougnez C, Onofrio R, Ambrogio L, Auclair D, Fennell T, Carter SL, Drier Y, Stojanov P, Singer MA, Voet D, Jing R, Saksena G, Barretina J, Ramos AH, Pugh TJ, Stransky N, Parkin M, Winckler W, Mahan S, Ardlie K, Baldwin J, Wargo J, Schadendorf D, Meyerson M, Gabriel SB, Golub TR, Wagner SN, Lander ES, Getz G, Chin L, Garraway LA Melanoma genome sequencing reveals frequent PREX2 mutations Nature 2012 May 6,18 Melanoma Next Generation Sequencing Homo sapiens ME020 Illumina HiSeq2000 chr10:0-106781190:0;chr10:106781191-106785684:-1;chr10:106785685-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-7272536:0;chr16:7272537-7313781:-1;chr16:7313782-90354753:0;chr17:0-13901959:0;chr17:13901960-14352662:1;chr17:14352663-81195210:0;chr18:0-30390957:0;chr18:30390958-30434395:-1;chr18:30434396-41115065:0;chr18:41115066-41137288:-1;chr18:41137289-54582240:0;chr18:54582241-54601567:-1;chr18:54601568-61151888:0;chr18:61151889-61960835:-1;chr18:61960836-78077248:0;chr19:0-59128983:0;chr1:0-216624610:0;chr1:216624611-216634039:-1;chr1:216634040-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-8612211:0;chr2:8612212-8646334:-1;chr2:8646335-243199373:0;chr3:0-15622615:0;chr3:15622616-15839069:1;chr3:15839070-198022430:0;chr4:0-177288198:0;chr4:177288199-177313813:-1;chr4:177313814-191154276:0;chr5:0-180915260:0;chr6:0-2822663:0;chr6:23340660-24176390:-1;chr6:24176391-30676240:0;chr6:2822664-2825594:-1;chr6:2825595-23340659:0;chr6:30676241-30679025:-1;chr6:30679026-32938466:0;chr6:32938467-32946578:-1;chr6:32946579-171115067:0;chr7:0-44122813:0;chr7:112684470-112965616:-1;chr7:112685216-112735909:1;chr7:112965617-159138663:0;chr7:44122814-44127168:-1;chr7:44127169-112684469:0;chr8:0-111114002:0;chr8:111114003-111115146:-1;chr8:111115147-146364022:0;chr9:0-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs1:9103916-9103916,hs1:9105932-9105932;hs1:41260951-41260951,hs1:41262403-41262403;hs1:46314569-46314569,hs1:46316968-46316968;hs1:72181667-72181667,hs1:72184200-72184200;hs1:106355204-106355204,hs1:106359919-106359919;hs1:160485624-160485624,hs1:160495808-160495808;hs1:189322814-189322814,hs1:189324518-189324518;hs1:215867806-215867806,hs1:215869113-215869113;hs1:246331007-246331007,hs1:246333198-246333198;hs2:34926198-34926198,hs2:34927805-34927805;hs2:65645820-65645820,hs2:65647159-65647159;hs2:88666373-88666373,hs2:88668047-88668047;hs2:121039959-121039959,hs2:121042150-121042150;hs2:124256294-124256294,hs2:124257977-124257977;hs2:142335927-142335927,hs2:142337316-142337316;hs2:230014680-230014680,hs2:230016584-230016584;hs3:7170392-7170392,hs3:7172139-7172139;hs3:14578606-14578606,hs3:14580585-14580585;hs3:19078063-19078063,hs3:19079225-19079225;hs3:60141928-60141928,hs3:60144283-60144283;hs3:64970323-64970323,hs3:64971706-64971706;hs3:86131944-86131944,hs17:53607639-53607639;hs3:130431512-130431512,hs3:130432525-130432525;hs3:130502238-130502238,hs3:130503796-130503796;hs3:139597755-139597755,hs3:139603775-139603775;hs3:178646484-178646484,hs3:178658686-178658686;hs3:180258303-180258303,hs3:180264172-180264172;hs4:26645648-26645648,hs4:26653984-26653984;hs4:53205731-53205731,hs4:53207716-53207716;hs4:80271113-80271113,hs4:80272412-80272412;hs4:190655481-190655481,hs18:53541704-53541704;hs5:6510129-6510129,hs5:6511947-6511947;hs5:12295358-12295358,hs5:12305745-12305745;hs5:52010150-52010150,hs6:4941869-4941869;hs5:52010187-52010187,hs5:63077745-63077745;hs5:52013478-52013478,hs18:64032844-64032844;hs5:52640908-52640908,hs6:41444152-41444152;hs5:59344334-59344334,hs5:59346298-59346298;hs5:64884778-64884778,hs6:4938688-4938688;hs5:64899153-64899153,hs6:36315354-36315354;hs5:85011971-85011971,hs5:166984875-166984875;hs5:85012160-85012160,hs5:89064338-89064338;hs5:85014203-85014203,hs5:89067723-89067723;hs5:85845011-85845011,hs5:153838798-153838798;hs5:88592503-88592503,hs5:163308447-163308447;hs5:90292079-90292079,hs5:151878477-151878477;hs5:101223742-101223742,hs5:149252355-149252355;hs5:121603274-121603274,hs5:121621910-121621910;hs5:131805363-131805363,hs5:131809549-131809549;hs5:139880940-139880940,hs5:168120778-168120778;hs5:140047467-140047467,hs5:154417681-154417681;hs5:170852697-170852697,hs5:170854057-170854057;hs5:176960992-176960992,hs18:67726295-67726295;hs6:513001-513001,hs6:15338526-15338526;hs6:546895-546895,hs6:13340396-13340396;hs6:1127207-1127207,hs18:63946292-63946292;hs6:1204014-1204014,hs6:2823453-2823453;hs6:1214543-1214543,hs6:8839757-8839757;hs6:1249900-1249900,hs6:10980571-10980571;hs6:1275263-1275263,hs6:12867018-12867018;hs6:1837394-1837394,hs18:35943205-35943205;hs6:1863588-1863588,hs6:9018016-9018016;hs6:2148808-2148808,hs17:14215274-14215274;hs6:2149610-2149610,hs6:10130581-10130581;hs6:2248141-2248141,hs18:61524007-61524007;hs6:2277706-2277706,hs6:4345725-4345725;hs6:2512715-2512715,hs18:64024570-64024570;hs6:2538540-2538540,hs6:10671096-10671096;hs6:2654722-2654722,hs6:4954365-4954365;hs6:2759788-2759788,hs6:9858332-9858332;hs6:2778803-2778803,hs18:34316615-34316615;hs6:2785247-2785247,hs18:64146744-64146744;hs6:2805455-2805455,hs6:17059886-17059886;hs6:2816055-2816055,hs6:17149712-17149712;hs6:2816432-2816432,hs6:10801356-10801356;hs6:3135468-3135468,hs18:48037065-48037065;hs6:3401978-3401978,hs18:48021817-48021817;hs6:3635376-3635376,hs6:17097292-17097292;hs6:3664407-3664407,hs6:10801530-10801530;hs6:3664611-3664611,hs6:10800990-10800990;hs6:3913413-3913413,hs6:17403414-17403414;hs6:3925618-3925618,hs18:67316513-67316513;hs6:3932251-3932251,hs6:47438862-47438862;hs6:4086270-4086270,hs6:6818933-6818933;hs6:4092731-4092731,hs6:17253704-17253704;hs6:4340953-4340953,hs18:21129135-21129135;hs6:4489604-4489604,hs6:41327397-41327397;hs6:4492282-4492282,hs18:35207259-35207259;hs6:4498713-4498713,hs18:33758143-33758143;hs6:4690146-4690146,hs6:36788444-36788444;hs6:4767017-4767017,hs18:64127839-64127839;hs6:4774222-4774222,hs6:41448919-41448919;hs6:4805949-4805949,hs18:39278596-39278596;hs6:4943196-4943196,hs18:64027937-64027937;hs6:6147024-6147024,hs18:52264657-52264657;hs6:6160814-6160814,hs6:9924179-9924179;hs6:6548260-6548260,hs6:17235081-17235081;hs6:6576934-6576934,hs18:41428831-41428831;hs6:6591137-6591137,hs18:44153300-44153300;hs6:6962379-6962379,hs18:48934659-48934659;hs6:6978611-6978611,hs6:56224654-56224654;hs6:6990139-6990139,hs6:48507254-48507254;hs6:7024146-7024146,hs6:33578065-33578065;hs6:7442708-7442708,hs6:12718225-12718225;hs6:7533800-7533800,hs6:13688938-13688938;hs6:7537824-7537824,hs6:56320042-56320042;hs6:7545781-7545781,hs6:29796841-29796841;hs6:7563834-7563834,hs6:32093161-32093161;hs6:7573964-7573964,hs18:21128464-21128464;hs6:7579830-7579830,hs18:68152901-68152901;hs6:7584000-7584000,hs6:10764994-10764994;hs6:7936108-7936108,hs18:39545422-39545422;hs6:8178573-8178573,hs18:66674466-66674466;hs6:8367985-8367985,hs6:17150104-17150104;hs6:8507441-8507441,hs6:37017653-37017653;hs6:8519674-8519674,hs6:12839720-12839720;hs6:8549665-8549665,hs18:26272812-26272812;hs6:8550923-8550923,hs18:66597853-66597853;hs6:8691401-8691401,hs18:48157490-48157490;hs6:9124648-9124648,hs18:33009022-33009022;hs6:9792664-9792664,hs18:64784923-64784923;hs6:9792921-9792921,hs18:34006760-34006760;hs6:9805862-9805862,hs18:39494971-39494971;hs6:9941600-9941600,hs6:10128565-10128565;hs6:9941610-9941610,hs6:36804961-36804961;hs6:9945918-9945918,hs18:62722104-62722104;hs6:10128572-10128572,hs6:36804848-36804848;hs6:10603303-10603303,hs18:48377620-48377620;hs6:10687608-10687608,hs18:52253377-52253377;hs6:10836142-10836142,hs18:64618044-64618044;hs6:10982675-10982675,hs18:64142773-64142773;hs6:11140102-11140102,hs6:16363836-16363836;hs6:12284339-12284339,hs18:40609665-40609665;hs6:12292452-12292452,hs18:33113948-33113948;hs6:12296546-12296546,hs18:35427544-35427544;hs6:12305068-12305068,hs6:24554367-24554367;hs6:12643184-12643184,hs18:34006029-34006029;hs6:12720840-12720840,hs18:29418331-29418331;hs6:13339977-13339977,hs6:42103041-42103041;hs6:13339983-13339983,hs18:42047004-42047004;hs6:13401781-13401781,hs21:11077039-11077039;hs6:14030522-14030522,hs18:41436912-41436912;hs6:14264329-14264329,hs6:23300922-23300922;hs6:15347515-15347515,hs6:16097207-16097207;hs6:15528174-15528174,hs18:49519946-49519946;hs6:15528190-15528190,hs18:44532581-44532581;hs6:15568848-15568848,hs18:42051548-42051548;hs6:15581542-15581542,hs18:68118495-68118495;hs6:17243945-17243945,hs6:18880726-18880726;hs6:17449961-17449961,hs18:21000001-21000001;hs6:17449963-17449963,hs6:23340680-23340680;hs6:18553834-18553834,hs6:18557069-18557069;hs6:18556608-18556608,hs18:68118512-68118512;hs6:18561466-18561466,hs18:42053468-42053468;hs6:18562995-18562995,hs6:20143366-20143366;hs6:18563751-18563751,hs18:41426615-41426615;hs6:18793817-18793817,hs18:42355590-42355590;hs6:19354865-19354865,hs6:54267477-54267477;hs6:19416962-19416962,hs18:48993053-48993053;hs6:24567468-24567468,hs18:41139138-41139138;hs6:24690948-24690948,hs18:21000784-21000784;hs6:26659449-26659449,hs18:61689520-61689520;hs6:28250022-28250022,hs6:32694537-32694537;hs6:28431190-28431190,hs6:28433446-28433446;hs6:29415499-29415499,hs21:16548400-16548400;hs6:29415805-29415805,hs6:32937601-32937601;hs6:29782640-29782640,hs6:56310078-56310078;hs6:29820098-29820098,hs17:22203716-22203716;hs6:29993791-29993791,hs6:29997639-29997639;hs6:30723411-30723411,hs6:53290708-53290708;hs6:30856921-30856921,hs6:32095933-32095933;hs6:32218497-32218497,hs6:36595745-36595745;hs6:32671049-32671049,hs6:52816360-52816360;hs6:32913001-32913001,hs18:48091438-48091438;hs6:34053659-34053659,hs18:64032956-64032956;hs6:34811257-34811257,hs6:38543206-38543206;hs6:34850327-34850327,hs6:38548848-38548848;hs6:36545374-36545374,hs17:14215211-14215211;hs6:36555515-36555515,hs18:62665458-62665458;hs6:36569864-36569864,hs18:62665614-62665614;hs6:36593952-36593952,hs18:48779826-48779826;hs6:36602163-36602163,hs18:48952388-48952388;hs6:36626445-36626445,hs6:54424940-54424940;hs6:36787936-36787936,hs18:45662200-45662200;hs6:36805920-36805920,hs18:62739260-62739260;hs6:36885770-36885770,hs18:62244509-62244509;hs6:38545325-38545325,hs18:48377914-48377914;hs6:38550592-38550592,hs18:49635373-49635373;hs6:41309523-41309523,hs18:42531608-42531608;hs6:41343108-41343108,hs6:54361064-54361064;hs6:42200351-42200351,hs18:32940550-32940550;hs6:42606290-42606290,hs18:42357917-42357917;hs6:45934080-45934080,hs18:52263713-52263713;hs6:45939573-45939573,hs18:48275695-48275695;hs6:47505936-47505936,hs18:39373569-39373569;hs6:70036272-70036272,hs18:45266821-45266821;hs6:122061343-122061343,hs6:122063570-122063570;hs7:19075502-19075502,hs7:19089750-19089750;hs7:24384107-24384107,hs7:24386944-24386944;hs7:112684676-112684676,hs7:142458015-142458015;hs7:112733754-112733754,hs7:142795423-142795423;hs7:112964285-112964285,hs7:142461627-142461627;hs7:122546377-122546377,hs7:122550538-122550538;hs7:157063925-157063925,hs7:157065295-157065295;hs8:11694038-11694038,hs13:45931392-45931392;hs8:33488710-33488710,hs8:33492785-33492785;hs8:67768321-67768321,hs8:67770619-67770619;hs8:98508900-98508900,hs8:98512955-98512955;hs8:138598771-138598771,hs8:138600791-138600791;hs9:10147758-10147758,hs9:10149846-10149846;hs9:27541369-27541369,hs9:27544011-27544011;hs9:29722862-29722862,hs9:29728205-29728205;hs9:132531501-132531501,hs9:132532658-132532658;hs9:137907335-137907335,hs21:24426716-24426716;hs10:25353948-25353948,hs10:25355821-25355821;hs11:48424239-48424239,hs11:48437561-48437561;hs12:10628595-10628595,hs12:10637266-10637266;hs12:13743557-13743557,hs12:13747156-13747156;hs12:21300733-21300733,hs12:21314009-21314009;hs12:99342748-99342748,hs12:99344097-99344097;hs12:126835571-126835571,hs12:126837578-126837578;hs13:31773700-31773700,hs21:30685042-30685042;hs14:103722909-103722909,hs14:103726612-103726612;hs15:30910648-30910648,hs15:30913364-30913364;hs15:41975519-41975519,hs15:41978718-41978718;hs15:98492163-98492163,hs15:98494245-98494245;hs16:17743375-17743375,hs16:17746952-17746952;hs16:47463497-47463497,hs16:47464702-47464702;hs17:5250161-5250161,hs22:40791207-40791207;hs17:8752495-8752495,hs21:10421908-10421908;hs17:12862155-12862155,hs17:21339094-21339094;hs17:12879572-12879572,hs17:14179274-14179274;hs17:13800355-13800355,hs21:22175490-22175490;hs17:13902407-13902407,hs17:14208839-14208839;hs17:14207538-14207538,hs18:22360643-22360643;hs17:14606026-14606026,hs17:14607211-14607211;hs17:18315072-18315072,hs18:48331377-48331377;hs17:66832262-66832262,hs17:68248789-68248789;hs18:12128495-12128495,hs18:72558553-72558553;hs18:18702081-18702081,hs18:49632157-49632157;hs18:18705752-18705752,hs18:52253772-52253772;hs18:20985936-20985936,hs18:67423420-67423420;hs18:22361544-22361544,hs18:45664172-45664172;hs18:22362689-22362689,hs18:62262990-62262990;hs18:25465970-25465970,hs18:33181204-33181204;hs18:25465975-25465975,hs18:33181163-33181163;hs18:25734109-25734109,hs18:66579983-66579983;hs18:26263158-26263158,hs18:67371940-67371940;hs18:28308853-28308853,hs18:28316571-28316571;hs18:30387488-30387488,hs18:30434037-30434037;hs18:30388860-30388860,hs18:30413459-30413459;hs18:33763301-33763301,hs18:67382340-67382340;hs18:36395249-36395249,hs18:40564047-40564047;hs18:40717519-40717519,hs18:45222623-45222623;hs18:40972177-40972177,hs18:45128142-45128142;hs18:41015621-41015621,hs18:42402244-42402244;hs18:42531324-42531324,hs18:42538819-42538819;hs18:44020788-44020788,hs18:49503410-49503410;hs18:45079932-45079932,hs18:48043702-48043702;hs18:45129635-45129635,hs18:61655199-61655199;hs18:45335456-45335456,hs18:62255937-62255937;hs18:46174137-46174137,hs18:62631948-62631948;hs18:51203471-51203471,hs18:61912855-61912855;hs18:58560884-58560884,hs18:61956795-61956795;hs18:61051094-61051094,hs18:65739243-65739243;hs18:61951148-61951148,hs18:67671324-67671324;hs19:20461593-20461593,hs19:20494575-20494575;hs21:14600261-14600261,hs21:23260852-23260852;hs21:15944462-15944462,hs21:19292512-19292512;hs21:16321017-16321017,hs21:22578442-22578442;hs21:20254895-20254895,hs21:27863211-27863211;hs21:22939475-22939475,hs21:24428479-24428479;hs22:31908766-31908766,hs22:31910435-31910435;hs22:45783656-45783656,hsX:2833611-2833611;hsX:5364354-5364354,hsX:5365626-5365626;hsX:38750549-38750549,hsX:38751978-38751978;hsY:6673036-6673036,hsY:6674295-6674295;hsY:7649419-7649419,hsY:7650749-7650749;hsY:19554866-19554866,hsY:19560448-19560448 ACOT13;ATF6B;ATXN1;BAI3;BPHL;BTBD9;C18orf20;C18orf26;C18orf34;C18orf45;C6orf10;C6orf132;C6orf138;C6orf145;C6orf195;C6orf201;C6orf52;C6orf89;C9orf72;CAP2;CCDC102B;CD2AP;CD83;CDH19;CDH2;CDH7;CDKN1A;CDYL;CELF4;CIDEA;CLIC5;CPNE5;DCC;DCDC2;DOK6;DSC3;DSP;DST;DTNBP1;EDN1;ELOVL2;ELP2;ETV7;EXOC2;F13A1;FAM50B;FGD2;FHOD3;FOXP4;FOXQ1;GALNT1;GCLC;GCNT2;GFOD1;GJA1;GMDS;GRM4;GSTA4;HDGFL1;HLA-G;HULC;ID4;INO80C;ITPR3;JARID2;KATNAL2;KC6;KIAA0319;KIAA0427;KIAA1012;KLHL14;LOC100190939;LOC221710;LOC284441;LOC285780;LOC339240;LOC401397;LOC647946;LOXHD1;LY86;MAK;MAPK4;MBD2;MBOAT1;MC4R;ME2;MEX3C;MIR548A1;MIR548A2;MOCOS;MRO;MYLIP;MYLK4;NCR2;NPC1;PECI;PGBD1;PHACTR1;PIK3C3;PIP5K1P1;RANBP9;RBM24;RIOK1;RIT2;RNF165;RNF182;ROCK1;RREB1;RTTN;SERPINB1;SERPINB2;SERPINB5;SERPINB8;SETBP1;SFRS3;SLC22A23;SLC35B3;SMAD2;SOCS6;SYT4;TAF11;TCF4;TFAP2A;TINAG;TRERF1;UBR2;UHRF1BP1;VPS4B;WDR7;WRNIP1;ZBTB7C;ZNF322A;ZNF396;ZNF407;ZNF521;ZSCAN23; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5-55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)--a PTEN-interacting protein and negative regulator of PTEN in breast cancer--as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma. GRCh37/hg19 phs000452 Yes ACOT13,C18orf45;C18orf45,DOK6;CAP2,C18orf45;CDH2,CCDC102B;CLIC5,C18orf26;DDR1,ATF6B;DSP,ATF6B;DSP,HLA;DSP,MAK;DSP,NPC1;DTNBP1,KATNAL2;EXOC2,JARID2;F13A1,C18orf26;LY86,LOXHD1;NCR2,SETBP1;PHACTR1,KIAA1012;TAF11,BTBD9;UBR2,SETBP1;UHRF1BP1,BTBD9;WRNIP1,FHOD3 CTDB0341 Research 22622578 Berger MF, Hodis E, Heffernan TP, Deribe YL, Lawrence MS, Protopopov A, Ivanova E, Watson IR, Nickerson E, Ghosh P, Zhang H, Zeid R, Ren X, Cibulskis K, Sivachenko AY, Wagle N, Sucker A, Sougnez C, Onofrio R, Ambrogio L, Auclair D, Fennell T, Carter SL, Drier Y, Stojanov P, Singer MA, Voet D, Jing R, Saksena G, Barretina J, Ramos AH, Pugh TJ, Stransky N, Parkin M, Winckler W, Mahan S, Ardlie K, Baldwin J, Wargo J, Schadendorf D, Meyerson M, Gabriel SB, Golub TR, Wagner SN, Lander ES, Getz G, Chin L, Garraway LA Melanoma genome sequencing reveals frequent PREX2 mutations Nature 2012 May 5,22 Melanoma Next Generation Sequencing Homo sapiens ME035 Illumina HiSeq2000 chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-103336094:0;chr14:103336095-103505623:1;chr14:103505624-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-58014519:0;chr17:58014520-58030611:-1;chr17:58030612-58031370:0;chr17:58031371-58033330:-1;chr17:58033331-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-9805643:0;chr1:160610796-160620905:-1;chr1:160620906-249250621:0;chr1:9805644-9983935:-1;chr1:9983936-160610795:0;chr20:0-63025520:0;chr21:0-26545901:0;chr21:26545902-26580567:-1;chr21:26580568-48129895:0;chr22:0-20927907:0;chr22:20927908-20949578:-1;chr22:20949579-23747545:0;chr22:23747546-23966618:-1;chr22:23966619-51304566:0;chr2:0-187180806:0;chr2:187180807-187183014:-1;chr2:187183015-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-54748906:0;chr5:54748907-54971031:1;chr5:54971032-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-124567394:0;chr8:124567395-124569744:-1;chr8:124569745-146364022:0;chr9:0-141213431:0;chrX:0-15409547:0;chrX:15409548-15686130:1;chrX:15668652-15686120:-1;chrX:15684400-15686346:1;chrX:15686347-155270560:0;chrY:0-59373566:0 hs1:8655029-8655029,hs1:8657168-8657168;hs1:49798993-49798993,hs1:49801451-49801451;hs1:53382625-53382625,hs1:53383890-53383890;hs1:64693342-64693342,hs1:64694621-64694621;hs1:101117401-101117401,hs1:101130085-101130085;hs1:143512806-143512806,hs5:38417994-38417994;hs1:144931335-144931335,hs2:46762281-46762281;hs1:144931335-144931335,hs2:46762281-46762281;hs1:176883763-176883763,hs1:181693108-181693108;hs1:185550047-185550047,hs1:185558527-185558527;hs1:210105649-210105649,hs1:210107267-210107267;hs1:240223859-240223859,hs1:240226433-240226433;hs2:53074337-53074337,hs2:53083656-53083656;hs2:72748919-72748919,hs2:72750717-72750717;hs2:115153642-115153642,hs2:115155467-115155467;hs3:81242-81242,hs3:1921867-1921867;hs3:35135645-35135645,hs3:35137473-35137473;hs3:57917588-57917588,hs3:57921021-57921021;hs3:106501624-106501624,hs3:106504144-106504144;hs3:113193251-113193251,hs3:113203874-113203874;hs3:146034612-146034612,hs3:146040410-146040410;hs3:177328083-177328083,hs3:177330243-177330243;hs3:180513096-180513096,hs3:180517204-180517204;hs4:154243429-154243429,hs4:154244692-154244692;hs5:485618-485618,hs22:17206980-17206980;hs5:512468-512468,hs5:28161882-28161882;hs5:518260-518260,hs5:36369866-36369866;hs5:841498-841498,hs5:35478937-35478937;hs5:1057413-1057413,hs5:21221208-21221208;hs5:1075488-1075488,hs22:48659248-48659248;hs5:1075528-1075528,hs22:18341455-18341455;hs5:1146423-1146423,hs5:2797971-2797971;hs5:1153000-1153000,hs5:21472495-21472495;hs5:1181561-1181561,hs5:31251355-31251355;hs5:1182536-1182536,hs22:50780201-50780201;hs5:1254824-1254824,hs22:40248068-40248068;hs5:1271870-1271870,hs5:3872609-3872609;hs5:1272275-1272275,hs5:53662217-53662217;hs5:1287439-1287439,hs5:49815427-49815427;hs5:1307328-1307328,hs22:37421558-37421558;hs5:1308446-1308446,hs5:23210371-23210371;hs5:1310046-1310046,hs5:28779106-28779106;hs5:1311657-1311657,hs22:37038541-37038541;hs5:1316192-1316192,hs5:23303899-23303899;hs5:1323567-1323567,hs5:20043814-20043814;hs5:1549749-1549749,hs22:18925485-18925485;hs5:1668570-1668570,hs22:21071046-21071046;hs5:1675555-1675555,hs22:40242354-40242354;hs5:1675908-1675908,hs22:20951086-20951086;hs5:1676289-1676289,hs5:36682095-36682095;hs5:1680592-1680592,hs5:36635679-36635679;hs5:1687983-1687983,hs22:20970717-20970717;hs5:1689528-1689528,hs5:23307560-23307560;hs5:1690969-1690969,hs5:9395950-9395950;hs5:1698340-1698340,hs5:23287905-23287905;hs5:1717674-1717674,hs22:18084499-18084499;hs5:1723774-1723774,hs5:53657758-53657758;hs5:1748718-1748718,hs22:33919289-33919289;hs5:2799749-2799749,hs22:49946492-49946492;hs5:3872302-3872302,hs5:5351020-5351020;hs5:3884443-3884443,hs5:4128717-4128717;hs5:3886206-3886206,hs22:20862880-20862880;hs5:3890639-3890639,hs5:5121579-5121579;hs5:3929861-3929861,hs5:32074678-32074678;hs5:4098909-4098909,hs5:21264652-21264652;hs5:4117048-4117048,hs22:51005572-51005572;hs5:4124493-4124493,hs5:19903666-19903666;hs5:5092489-5092489,hs5:9512605-9512605;hs5:5352515-5352515,hs5:31246269-31246269;hs5:5359964-5359964,hs5:9488557-9488557;hs5:5383859-5383859,hs22:17905943-17905943;hs5:5385062-5385062,hs22:20962595-20962595;hs5:5392080-5392080,hs22:19901110-19901110;hs5:5399802-5399802,hs5:35711677-35711677;hs5:5401503-5401503,hs5:28160458-28160458;hs5:5402565-5402565,hs22:49974409-49974409;hs5:5568139-5568139,hs5:31911774-31911774;hs5:9502216-9502216,hs5:53661253-53661253;hs5:9502760-9502760,hs5:21405801-21405801;hs5:9509516-9509516,hs5:23457270-23457270;hs5:9554937-9554937,hs22:37416227-37416227;hs5:11444653-11444653,hs5:11446174-11446174;hs5:13162833-13162833,hs5:44084898-44084898;hs5:13400528-13400528,hs5:32078369-32078369;hs5:13401841-13401841,hs22:20880879-20880879;hs5:13556250-13556250,hs5:32078551-32078551;hs5:13563174-13563174,hs5:49804975-49804975;hs5:13564727-13564727,hs5:26928343-26928343;hs5:13569561-13569561,hs5:43561719-43561719;hs5:13570485-13570485,hs5:28770109-28770109;hs5:13576599-13576599,hs5:23201072-23201072;hs5:13994607-13994607,hs22:49162743-49162743;hs5:13994633-13994633,hs5:23467800-23467800;hs5:20085144-20085144,hs5:32205435-32205435;hs5:20136777-20136777,hs5:23495124-23495124;hs5:20165566-20165566,hs5:38075454-38075454;hs5:20271150-20271150,hs5:28786635-28786635;hs5:21469520-21469520,hs22:49146760-49146760;hs5:21648679-21648679,hs5:25958187-25958187;hs5:21818919-21818919,hs22:35655510-35655510;hs5:22065197-22065197,hs5:36632709-36632709;hs5:22922717-22922717,hs5:28750480-28750480;hs5:23168011-23168011,hs5:27802049-27802049;hs5:23168679-23168679,hs22:33914363-33914363;hs5:23197320-23197320,hs5:32082252-32082252;hs5:23197967-23197967,hs5:26934812-26934812;hs5:23235684-23235684,hs5:53622648-53622648;hs5:23272122-23272122,hs5:26935346-26935346;hs5:23272238-23272238,hs22:20950185-20950185;hs5:23286642-23286642,hs22:20952551-20952551;hs5:23294904-23294904,hs5:36849191-36849191;hs5:23297847-23297847,hs22:19012573-19012573;hs5:23305047-23305047,hs5:36633904-36633904;hs5:23305877-23305877,hs22:49988174-49988174;hs5:23309294-23309294,hs22:16433038-16433038;hs5:23317010-23317010,hs19:24540697-24540697;hs5:23355382-23355382,hs5:29127940-29127940;hs5:23362265-23362265,hs5:27794324-27794324;hs5:23439352-23439352,hs22:17807299-17807299;hs5:23465956-23465956,hs5:36634254-36634254;hs5:24785099-24785099,hs22:37062994-37062994;hs5:25794769-25794769,hs17:25293594-25293594;hs5:25798482-25798482,hs5:37968834-37968834;hs5:25970413-25970413,hs5:38398612-38398612;hs5:25970576-25970576,hs5:36471591-36471591;hs5:26138641-26138641,hs5:36637856-36637856;hs5:26139355-26139355,hs5:44059071-44059071;hs5:26931757-26931757,hs22:20951270-20951270;hs5:26936274-26936274,hs5:38404452-38404452;hs5:27713264-27713264,hs5:32049935-32049935;hs5:27719405-27719405,hs22:20950475-20950475;hs5:27720584-27720584,hs5:36476126-36476126;hs5:27721782-27721782,hs22:19875132-19875132;hs5:27723216-27723216,hs5:49661199-49661199;hs5:27789614-27789614,hs5:38406036-38406036;hs5:27795505-27795505,hs5:38403379-38403379;hs5:27796754-27796754,hs22:37435176-37435176;hs5:27802680-27802680,hs5:30693469-30693469;hs5:28155850-28155850,hs22:22511232-22511232;hs5:28156025-28156025,hs22:20840916-20840916;hs5:28164067-28164067,hs5:35758257-35758257;hs5:28166009-28166009,hs5:36470076-36470076;hs5:28170894-28170894,hs22:19009083-19009083;hs5:28173132-28173132,hs5:36629429-36629429;hs5:28780202-28780202,hs22:20844656-20844656;hs5:28781053-28781053,hs22:33900481-33900481;hs5:29121650-29121650,hs5:37950436-37950436;hs5:29128530-29128530,hs22:50774929-50774929;hs5:29410018-29410018,hs5:31908371-31908371;hs5:30210599-30210599,hs22:20827891-20827891;hs5:30633722-30633722,hs5:43499296-43499296;hs5:30634374-30634374,hs22:37249348-37249348;hs5:30637290-30637290,hs21:11167304-11167304;hs5:30693877-30693877,hs5:36632288-36632288;hs5:30851740-30851740,hs22:50296383-50296383;hs5:31249786-31249786,hs22:20921444-20921444;hs5:31252125-31252125,hs5:32497542-32497542;hs5:31441759-31441759,hs5:35761725-35761725;hs5:31628866-31628866,hs22:51001261-51001261;hs5:31631691-31631691,hs22:37036347-37036347;hs5:32035482-32035482,hs5:49661450-49661450;hs5:32035935-32035935,hs5:38135135-38135135;hs5:32072026-32072026,hs5:49821802-49821802;hs5:32080244-32080244,hs22:33915782-33915782;hs5:32198766-32198766,hs22:20962824-20962824;hs5:35485448-35485448,hs22:40019467-40019467;hs5:35710601-35710601,hs5:43930818-43930818;hs5:35762211-35762211,hs5:49805325-49805325;hs5:35910256-35910256,hs22:17209355-17209355;hs5:35910580-35910580,hs5:49806802-49806802;hs5:35946647-35946647,hs22:17806122-17806122;hs5:36199228-36199228,hs5:42992275-42992275;hs5:36370859-36370859,hs22:20798806-20798806;hs5:36466062-36466062,hs5:38189762-38189762;hs5:36482705-36482705,hs22:18129293-18129293;hs5:36486626-36486626,hs22:35931574-35931574;hs5:36513018-36513018,hs5:43464840-43464840;hs5:36631763-36631763,hs5:49825420-49825420;hs5:36834057-36834057,hs22:50768708-50768708;hs5:36849670-36849670,hs5:53675841-53675841;hs5:37093299-37093299,hs22:49769931-49769931;hs5:37912961-37912961,hs22:29256097-29256097;hs5:37966328-37966328,hs22:40250056-40250056;hs5:38052987-38052987,hs22:40250767-40250767;hs5:38061352-38061352,hs22:48840549-48840549;hs5:38064009-38064009,hs22:18913414-18913414;hs5:38065141-38065141,hs22:49966512-49966512;hs5:38095358-38095358,hs22:22499014-22499014;hs5:38095715-38095715,hs5:43483568-43483568;hs5:38096943-38096943,hs22:33899780-33899780;hs5:38104996-38104996,hs22:40248841-40248841;hs5:38114337-38114337,hs5:43519044-43519044;hs5:38114673-38114673,hs5:42993812-42993812;hs5:38384255-38384255,hs5:38559813-38559813;hs5:38404174-38404174,hs5:49822497-49822497;hs5:38407541-38407541,hs22:18130866-18130866;hs5:38578459-38578459,hs5:43070276-43070276;hs5:38638664-38638664,hs22:19950081-19950081;hs5:38968534-38968534,hs5:42709647-42709647;hs5:42910830-42910830,hs5:43004733-43004733;hs5:42990508-42990508,hs21:11094174-11094174;hs5:43000653-43000653,hs22:19010588-19010588;hs5:43074982-43074982,hs5:43158643-43158643;hs5:43089919-43089919,hs22:20879876-20879876;hs5:43125042-43125042,hs22:40230297-40230297;hs5:43159406-43159406,hs5:53696538-53696538;hs5:43930410-43930410,hs22:20951587-20951587;hs5:44046816-44046816,hs22:18225386-18225386;hs5:49801634-49801634,hs17:25294650-25294650;hs5:53263445-53263445,hs22:36319135-36319135;hs5:53636796-53636796,hs14:19122500-19122500;hs5:53663907-53663907,hs22:18134758-18134758;hs5:53701658-53701658,hs22:20861051-20861051;hs5:54969910-54969910,hs5:141210259-141210259;hs5:107887570-107887570,hs5:107907193-107907193;hs5:161438641-161438641,hs5:161440942-161440942;hs6:3902506-3902506,hs6:3903968-3903968;hs6:11401430-11401430,hs6:12917201-12917201;hs6:11401431-11401431,hs6:12917202-12917202;hs6:40821523-40821523,hs6:50011491-50011491;hs6:40821523-40821523,hs6:50011491-50011491;hs6:82761285-82761285,hs6:90092933-90092933;hs6:134529553-134529553,hs6:146347793-146347793;hs6:134529584-134529584,hs6:146347760-146347760;hs7:140150627-140150627,hs7:140152136-140152136;hs7:140751433-140751433,hs7:140754562-140754562;hs8:38232337-38232337,hs8:38234117-38234117;hs9:14360794-14360794,hs9:14362652-14362652;hs10:7661118-7661118,hs10:7682910-7682910;hs10:45075972-45075972,hs10:76390138-76390138;hs10:122326286-122326286,hs10:122328476-122328476;hs11:78326613-78326613,hs11:78329618-78329618;hs12:97554102-97554102,hs12:97556165-97556165;hs13:21659980-21659980,hs13:21661601-21661601;hs13:56305339-56305339,hs13:56310281-56310281;hs13:87969242-87969242,hs13:87970513-87970513;hs13:102206614-102206614,hs13:102208522-102208522;hs14:19115977-19115977,hs22:20803440-20803440;hs14:19122213-19122213,hs22:17941634-17941634;hs14:101994465-101994465,hs14:101996329-101996329;hs15:28495070-28495070,hs15:28496774-28496774;hs15:69931004-69931004,hs15:69934976-69934976;hs15:90935994-90935994,hs15:90937215-90937215;hs15:99584068-99584068,hs15:99585424-99585424;hs16:29673791-29673791,hs16:29676655-29676655;hs16:80563880-80563880,hs16:80565915-80565915;hs17:10952381-10952381,hs17:10954034-10954034;hs17:48926659-48926659,hs17:48928893-48928893;hs17:57868324-57868324,hs17:58014507-58014507;hs17:58015030-58015030,hs17:58033583-58033583;hs17:62408850-62408850,hs17:62410355-62410355;hs20:8563532-8563532,hs20:8565556-8565556;hs20:45864450-45864450,hs20:45865957-45865957;hs21:36674674-36674674,hs21:36675887-36675887;hs22:17200351-17200351,hs22:18353739-18353739;hs22:17590743-17590743,hs22:40225630-40225630;hs22:17591653-17591653,hs22:20880011-20880011;hs22:17920404-17920404,hs22:20866559-20866559;hs22:17923568-17923568,hs22:40152597-40152597;hs22:18227029-18227029,hs22:19767292-19767292;hs22:18342300-18342300,hs22:40078760-40078760;hs22:18354510-18354510,hs22:20839917-20839917;hs22:18365637-18365637,hs22:50280741-50280741;hs22:18909979-18909979,hs22:20918705-20918705;hs22:19007764-19007764,hs22:40241583-40241583;hs22:20820621-20820621,hs22:20997676-20997676;hs22:20822774-20822774,hs22:40230641-40230641;hs22:20850001-20850001,hs22:37257204-37257204;hs22:20881449-20881449,hs22:40260601-40260601;hs22:20922213-20922213,hs22:50767503-50767503;hs22:21031824-21031824,hs22:37422419-37422419;hs22:21078212-21078212,hs22:40062989-40062989;hs22:22312208-22312208,hs22:37037429-37037429;hs22:22513442-22513442,hs22:50807542-50807542;hs22:29250551-29250551,hs22:40184723-40184723;hs22:33893290-33893290,hs22:37248274-37248274;hs22:37259262-37259262,hs22:49969089-49969089;hs22:40064802-40064802,hs22:51150888-51150888;hs22:40246937-40246937,hs22:50773844-50773844;hs22:48653305-48653305,hs22:49164239-49164239;hs22:48664827-48664827,hs22:51101730-51101730;hs22:48667983-48667983,hs22:49771154-49771154;hsX:29998570-29998570,hsX:31400781-31400781;hsX:103748760-103748760,hsX:103750402-103750402;hsX:110902534-110902534,hsX:110903640-110903640;hsY:8542239-8542239,hsY:8547082-8547082 ADAMTS16;ALG12;ARL15;ASB3;ATP6V1E1;BAGE;BCL2L13;BID;C21orf96;C22orf34;C22orf41;C22orf43;C5orf22;C5orf28;C5orf33;C5orf34;C5orf38;C5orf39;C5orf42;CACNA1I;CACNG2;CAPSL;CDH10;CDH12;CDH18;CDH6;CDH9;CECR1;CECR2;COMT;CPT1B;CTNND2;DGCR10;DNAH5;EGFLAM;ENTHD1;FAM116B;FAM19A5;FER;FGF10;GABRG2;GDNF;GHR;GUSBP1;HMGXB4;HSPB3;IL17RA;IRX1;KCTD17;KIAA0947;KLHL22;LARGE;LIFR;LOC100101266;LOC100130000;LOC100302640;LOC145837;MED15;MICAL3;MPST;MRPL36;MTMR12;NCF4;NIPBL;NNT;OR11H1;PAIP1;PCDH1;PDZD2;PI4KA;POM121L4P;PPAP2A;PRDM9;PRODH;RANBP3L;RASD2;RBM9;RICTOR;RNASEN;SAPS2;SDHAP3;SEMA5A;SEPP1;SHANK3;SLC1A3;SLC38A9;SLC6A19;SNORD123;SPEF2;TBX1;TERT;TOP3B;TXNRD2;UGT3A1;VPREB1;XKR3;ZBED4;ZDHHC11;ZDHHC8P1;ZFR;ZNF131;ZNRF3; The Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5-55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)--a PTEN-interacting protein and negative regulator of PTEN in breast cancer--as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma. GRCh37/hg19 phs000452 Yes ARL15,RBM9;BID,TBX1;CACNA1I,SHANK3;CDH12,HMGXB4;CDH12,SLC1A3;CDH6,MED15;CDH9,EGFLAM;DGCR10,ENTHD1;EGFLAM,BCL2L13;EGFLAM,LIFR;GUSBP1,FAM19A5;IL17RA,ENTHD1;KLHL22,ENTHD1;KLHL22,NCF4;MED15,ENTHD1;MED15,FAM116B;MICAL3,CACNA1I;MICAL3,KLHL22;MICAL3,ZBED4;PDZD2,LARGE;PI4KA,CACNA1I;PPAP2A,SLC38A9;PRODH,MED15;RICTOR,GHR;RNASEN,SPEF2;SLC12A7,MICAL3;TERT,ENTHD1;TOP3B,CACNG2;ZDHHC8P1,C22orf43;ZNF131,ENTHD1 CTDB0343 Research 24819516 Iannelli F, Collino A, Sinha S, Radaelli E, Nicoli P, D'Antiga L, Sonzogni A, Faivre J, Buendia MA, Sturm E, Thompson RJ, Knisely AS, Natoli G, Ghisletti S, Ciccarelli FD Massive gene amplification drives paediatric hepatocellular carcinoma caused by bile salt export pump deficiency Nature Communications 2014 May 19 Hepatocellular carcinoma Next Generation Sequencing Mus musculus 60400/1 Illumina Genome Analyzer Iix and Illumina HiSeq2000 chr10:0-25238100:0;chr10:117135301-117165300:-1;chr10:117165301-120861600:0;chr10:120861601-120950400:-1;chr10:120950401-126797700:0;chr10:126797701-126821700:-1;chr10:126821701-129993255:0;chr10:25238101-25271700:-1;chr10:25271701-53090100:0;chr10:53090101-53103000:-1;chr10:53103001-58751700:0;chr10:58751701-58768200:1;chr10:58768201-67687500:0;chr10:67687501-67752000:-1;chr10:67752001-67812600:0;chr10:67812601-67820100:-1;chr10:67820101-81003300:0;chr10:81003301-81027900:-1;chr10:81027901-86235000:0;chr10:86235001-86266500:-1;chr10:86266501-92612700:0;chr10:92612701-92650200:-1;chr10:92650201-92868300:0;chr10:92868301-92903700:-1;chr10:92903701-98654700:0;chr10:98654701-98670000:-1;chr10:98670001-98920800:0;chr10:98920801-98930100:-1;chr10:98930101-117135300:0;chr11:0-6489300:0;chr11:117169201-117204600:-1;chr11:117204601-118280400:0;chr11:118280401-118292100:-1;chr11:118292101-121843856:0;chr11:57901801-57921300:-1;chr11:57921301-62355300:0;chr11:62355301-62389200:-1;chr11:62389201-82662900:0;chr11:6489301-6506400:1;chr11:6506401-9217500:0;chr11:82662901-82709700:-1;chr11:82709701-90906000:0;chr11:90906001-90925500:1;chr11:90925501-117169200:0;chr11:9217501-9228600:-1;chr11:9228601-57901800:0;chr12:0-11085900:0;chr12:11085901-11119800:1;chr12:11119801-25767000:0;chr12:111251701-111269700:-1;chr12:111269701-114138900:0;chr12:114138901-114162900:1;chr12:114162901-121257530:0;chr12:25767001-25816200:-1;chr12:25816201-29316600:0;chr12:29316601-29325000:-1;chr12:29325001-33451800:0;chr12:33451801-33465300:-1;chr12:33465301-57960600:0;chr12:57960601-57971400:1;chr12:57971401-77862900:0;chr12:77862901-77889600:-1;chr12:77889601-80143500:0;chr12:80143501-80182200:1;chr12:80182201-81983700:0;chr12:81983701-82086600:-1;chr12:82086601-111251700:0;chr13:0-15457200:0;chr13:15457201-22106100:1;chr13:22106101-22122900:0;chr13:22122901-23514900:1;chr13:23514901-23542200:0;chr13:23542201-24883500:1;chr13:24883501-24935400:0;chr13:24935401-26344800:1;chr13:26344801-40931400:0;chr13:40931401-40958700:-1;chr13:40958701-84339300:0;chr13:84339301-84365700:-1;chr13:84365701-120284312:0;chr14:0-19614000:1;chr14:100623301-100654800:0;chr14:100654801-101046600:1;chr14:101046601-101055300:0;chr14:101055301-106677600:1;chr14:106677601-112769700:0;chr14:112769701-113011200:-1;chr14:113011201-125194864:0;chr14:19614001-22318800:0;chr14:22318801-23806200:1;chr14:23806201-23842500:0;chr14:23842501-26263200:1;chr14:26263201-26391900:0;chr14:26391901-26521200:1;chr14:26521201-28199100:0;chr14:28199101-32006700:1;chr14:32006701-32021700:0;chr14:32021701-32198400:1;chr14:32198401-32496900:0;chr14:32496901-34208100:1;chr14:34208101-34273200:0;chr14:34273201-35042400:1;chr14:35042401-35371200:0;chr14:35371201-35423700:1;chr14:35423701-35624700:0;chr14:35624701-38650800:1;chr14:38650801-46394700:0;chr14:46394701-46477200:1;chr14:46477201-46895100:0;chr14:46895101-47333400:1;chr14:47333401-47609400:0;chr14:47609401-47763300:1;chr14:47763301-48276000:0;chr14:48276001-48718500:1;chr14:48718501-48788100:0;chr14:48788101-50868900:1;chr14:50868901-51004800:0;chr14:51004801-51040800:1;chr14:51040801-51924000:0;chr14:51924001-51939600:1;chr14:51939601-53004300:0;chr14:53004301-53091600:1;chr14:53091601-54548700:0;chr14:54548701-55987500:-1;chr14:55987501-73367100:0;chr14:73367101-74166900:-1;chr14:74166901-87728700:0;chr14:87728701-88080300:-1;chr14:88080301-89046000:0;chr14:89046001-89661600:-1;chr14:89661601-89885700:0;chr14:89885701-90747000:-1;chr14:90747001-91337700:0;chr14:91337701-91578300:-1;chr14:91578301-92149200:0;chr14:92149201-92502000:-1;chr14:92502001-92782500:0;chr14:92782501-93204300:-1;chr14:93204301-94571400:0;chr14:94571401-94861800:-1;chr14:94861801-96496800:0;chr14:96496801-97255800:-1;chr14:97255801-99048900:0;chr14:99048901-100623300:1;chr15:0-8389200:0;chr15:102198901-102236100:-1;chr15:102236101-103494974:0;chr15:72361501-72374400:1;chr15:72374401-78500700:0;chr15:78500701-78526200:1;chr15:78526201-85458000:0;chr15:8389201-8400000:-1;chr15:8400001-72361500:0;chr15:85458001-85501200:-1;chr15:85501201-96112500:0;chr15:96112501-96125100:-1;chr15:96125101-96281700:0;chr15:96281701-96293100:-1;chr15:96293101-99196800:0;chr15:99196801-99248700:-1;chr15:99248701-99798000:0;chr15:99798001-99814200:-1;chr15:99814201-102198900:0;chr16:0-14452500:0;chr16:14452501-14484300:1;chr16:14484301-18396300:0;chr16:18396301-18405300:1;chr16:18405301-23975100:0;chr16:23975101-23996400:-1;chr16:23996401-30406500:0;chr16:30406501-30422700:-1;chr16:30422701-60600000:0;chr16:60600001-60624000:1;chr16:60624001-78174000:0;chr16:78174001-78201900:-1;chr16:78201901-98319150:0;chr17:0-23325000:0;chr17:23325001-23339700:-1;chr17:23339701-24672300:0;chr17:24672301-24697200:-1;chr17:24697201-27758100:0;chr17:27758101-27763500:-1;chr17:27763501-46993500:0;chr17:46993501-47053200:-1;chr17:47053201-50060700:0;chr17:50060701-50076600:1;chr17:50076601-56552700:0;chr17:56552701-56581200:1;chr17:56581201-93747300:0;chr17:93747301-95272651:1;chr17:95272652-95272651:0;chr18:0-14130000:1;chr18:14130001-14131800:0;chr18:14131801-17302500:1;chr18:17302501-17315400:0;chr18:17315401-21042300:1;chr18:21042301-21109200:0;chr18:21109201-24680700:1;chr18:24680701-24735300:0;chr18:24735301-29739000:1;chr18:29739001-30420900:0;chr18:30420901-30441900:-1;chr18:30441901-35717700:0;chr18:35717701-35731500:-1;chr18:35731501-80197200:0;chr18:80197201-80259000:1;chr18:80259001-80278200:0;chr18:80278201-80339700:1;chr18:80339701-80471400:0;chr18:80471401-81072300:1;chr18:81072301-81139800:0;chr18:81139801-82352700:1;chr18:82352701-82440600:0;chr18:82440601-82826400:1;chr18:82826401-82861800:0;chr18:82861801-84242700:1;chr18:84242701-84267900:0;chr18:84267901-84459600:1;chr18:84459601-86554800:0;chr18:86554801-87931800:1;chr18:87931801-90772031:0;chr19:0-4016700:0;chr19:14626501-14636400:-1;chr19:14636401-15398400:0;chr19:15398401-17296200:1;chr19:17296201-17328600:0;chr19:17328601-17351400:1;chr19:17351401-17573100:0;chr19:17573101-18087300:1;chr19:18087301-18927000:0;chr19:18927001-19929300:1;chr19:19929301-20118900:0;chr19:20118901-20211300:1;chr19:20211301-20235300:0;chr19:20235301-20275800:1;chr19:20275801-20881800:0;chr19:20881801-20941800:1;chr19:20941801-22058700:0;chr19:22058701-22228800:1;chr19:22228801-22233900:0;chr19:22233901-22796700:1;chr19:22796701-23571000:0;chr19:23571001-23752200:1;chr19:23752201-23770200:0;chr19:23770201-24221700:1;chr19:24221701-24362400:0;chr19:24362401-24928800:1;chr19:24928801-24966900:0;chr19:24966901-24981600:1;chr19:24981601-25483200:0;chr19:25483201-29112300:1;chr19:29112301-29758200:0;chr19:29758201-29807400:1;chr19:29807401-29916600:0;chr19:29916601-29933700:1;chr19:29933701-30846000:0;chr19:30846001-31125600:1;chr19:31125601-34564800:0;chr19:34564801-34636800:-1;chr19:34636801-37509900:0;chr19:37509901-37520700:-1;chr19:37520701-41472300:0;chr19:4016701-4081800:-1;chr19:4081801-6021600:0;chr19:41472301-41576700:-1;chr19:41576701-57419100:0;chr19:57419101-57459600:-1;chr19:57459601-61342430:0;chr19:6021601-6046800:-1;chr19:6046801-14626500:0;chr1:0-9722100:0;chr1:100609501-100669200:1;chr1:100669201-138579000:0;chr1:138579001-138597000:-1;chr1:138597001-155322300:0;chr1:155322301-155346900:-1;chr1:155346901-173362500:0;chr1:173362501-173436000:-1;chr1:173436001-187151400:0;chr1:187151401-187166700:-1;chr1:187166701-197195432:0;chr1:21303601-21310800:-1;chr1:21310801-29166900:0;chr1:29166901-29184000:-1;chr1:29184001-40066200:0;chr1:40066201-40097700:1;chr1:40097701-71694900:0;chr1:71694901-71707500:-1;chr1:71707501-100609500:0;chr1:9722101-9780900:-1;chr1:9780901-21303600:0;chr2:0-3391200:1;chr2:10425001-10440300:1;chr2:10440301-24921300:0;chr2:121857001-121865700:-1;chr2:121865701-122039700:0;chr2:122039701-122083500:-1;chr2:122083501-155962200:0;chr2:155962201-156069300:-1;chr2:156069301-165679500:0;chr2:165679501-165862500:-1;chr2:165862501-166782300:0;chr2:166782301-166845900:-1;chr2:166845901-181748087:0;chr2:24921301-24935400:-1;chr2:24935401-25570200:0;chr2:25570201-25597200:1;chr2:25597201-34579800:0;chr2:3391201-3410400:0;chr2:3410401-5456700:1;chr2:34579801-34614000:-1;chr2:34614001-71704500:0;chr2:5456701-6077100:0;chr2:6077101-6119100:1;chr2:6119101-6141300:0;chr2:6141301-7195500:1;chr2:71704501-71720700:-1;chr2:71720701-84722400:0;chr2:7195501-7220700:0;chr2:7220701-7454700:1;chr2:7454701-10425000:0;chr2:84722401-84764700:-1;chr2:84764701-121857000:0;chr3:0-7518900:-1;chr3:104311201-104347800:-1;chr3:104347801-116761800:0;chr3:10875601-10897500:1;chr3:10897501-67965900:0;chr3:116761801-116766900:-1;chr3:116766901-127477200:0;chr3:127477201-127508400:-1;chr3:127508401-132092400:0;chr3:132092401-132100500:1;chr3:132100501-159599783:0;chr3:67965901-67980000:-1;chr3:67980001-93371100:0;chr3:7518901-10875600:0;chr3:93371101-93380700:-1;chr3:93380701-95458800:0;chr3:95458801-95480700:-1;chr3:95480701-104311200:0;chr4:0-32174700:0;chr4:116510401-116521800:-1;chr4:116521801-116801700:0;chr4:116801701-116819700:-1;chr4:116819701-116851800:0;chr4:116851801-116928900:-1;chr4:116928901-132876300:0;chr4:132876301-132920400:-1;chr4:132920401-133101900:0;chr4:133101901-133134300:-1;chr4:133134301-133147200:0;chr4:133147201-133155300:-1;chr4:133155301-133353000:0;chr4:133353001-133387800:-1;chr4:133387801-134036400:0;chr4:134036401-134079300:-1;chr4:134079301-137132700:0;chr4:137132701-137154600:-1;chr4:137154601-137380200:0;chr4:137380201-137579100:-1;chr4:137579101-138679500:0;chr4:138679501-138711900:-1;chr4:138711901-141301500:0;chr4:141301501-141318000:-1;chr4:141318001-148647300:0;chr4:148647301-148699200:-1;chr4:148699201-148770600:0;chr4:148770601-148827000:-1;chr4:148827001-149142900:0;chr4:149142901-149184000:-1;chr4:149184001-155586600:0;chr4:155586601-155630120:1;chr4:155630121-155630120:0;chr4:32174701-32185800:-1;chr4:32185801-43963500:0;chr4:43963501-43990500:-1;chr4:43990501-45413100:0;chr4:45413101-45434100:-1;chr4:45434101-59568600:0;chr4:59568601-59599500:-1;chr4:59599501-62955600:0;chr4:62955601-62966400:1;chr4:62966401-116510400:0;chr5:0-7085400:1;chr5:101300401-101311800:-1;chr5:101311801-106113600:0;chr5:106113601-106128900:-1;chr5:106128901-108886800:0;chr5:108886801-108893400:-1;chr5:108893401-115913400:0;chr5:115913401-116023800:-1;chr5:116023801-119191800:0;chr5:119191801-119213700:1;chr5:119213701-121897200:0;chr5:121897201-121908600:-1;chr5:121908601-128090400:0;chr5:128090401-128147400:-1;chr5:128147401-136673100:0;chr5:136673101-136682700:-1;chr5:136682701-140227200:0;chr5:140227201-140249700:1;chr5:140249701-143695500:0;chr5:143695501-143708100:-1;chr5:143708101-144012900:0;chr5:144012901-144027600:1;chr5:144027601-151451700:0;chr5:151451701-151484400:-1;chr5:151484401-152537259:0;chr5:23334301-23355000:-1;chr5:23355001-24253200:0;chr5:24253201-24266100:-1;chr5:24266101-34334400:0;chr5:34334401-34364700:1;chr5:34364701-36897000:0;chr5:36897001-36904200:-1;chr5:36904201-44043000:0;chr5:44043001-44065800:-1;chr5:44065801-75430800:0;chr5:7085401-23334300:0;chr5:75430801-75448800:-1;chr5:75448801-101300400:0;chr6:0-9625800:1;chr6:108594601-108630300:-1;chr6:108630301-113571000:0;chr6:113571001-113651400:-1;chr6:113651401-117789900:0;chr6:117789901-117871800:-1;chr6:117871801-124738500:0;chr6:124738501-124764900:-1;chr6:124764901-141807300:0;chr6:141807301-141840300:-1;chr6:141840301-146837100:0;chr6:146837101-146879700:-1;chr6:146879701-149517037:0;chr6:26314201-26328000:-1;chr6:26328001-73150500:0;chr6:73150501-73206900:-1;chr6:73206901-108594600:0;chr6:9625801-26314200:0;chr7:0-16493100:0;chr7:104447701-104464500:1;chr7:104464501-149138400:0;chr7:149138401-149198100:1;chr7:149198101-152524553:0;chr7:16493101-16510800:-1;chr7:16510801-24889500:0;chr7:24889501-24892800:1;chr7:24892801-30872400:0;chr7:30872401-30882000:-1;chr7:30882001-52725600:0;chr7:52725601-52748700:-1;chr7:52748701-75407700:0;chr7:75407701-75465900:-1;chr7:75465901-86838600:0;chr7:86838601-86858100:1;chr7:86858101-104447700:0;chr8:0-7272300:1;chr8:102246001-102254100:1;chr8:102254101-111214200:0;chr8:111214201-111251400:-1;chr8:111251401-118218000:0;chr8:118218001-118244400:-1;chr8:118244401-123833700:0;chr8:123833701-123842100:1;chr8:123842101-124096200:0;chr8:124096201-124119000:-1;chr8:124119001-131738871:0;chr8:16017301-16041600:1;chr8:16041601-26704500:0;chr8:26704501-26732400:-1;chr8:26732401-42175200:0;chr8:42175201-42260700:-1;chr8:42260701-43308900:0;chr8:43308901-43335600:-1;chr8:43335601-48581100:0;chr8:48581101-48596100:1;chr8:48596101-52887600:0;chr8:52887601-52913100:-1;chr8:52913101-72852000:0;chr8:7272301-16017300:0;chr8:72852001-72867600:1;chr8:72867601-77591700:0;chr8:77591701-77635200:-1;chr8:77635201-91619400:0;chr8:91619401-91636200:-1;chr8:91636201-102246000:0;chr9:0-62244300:0;chr9:110528401-110549100:1;chr9:110549101-110881200:0;chr9:110881201-110899500:-1;chr9:110899501-119900400:0;chr9:119900401-119922000:-1;chr9:119922001-124076172:0;chr9:62244301-62271900:-1;chr9:62271901-64592100:0;chr9:64592101-64615800:-1;chr9:64615801-66395100:0;chr9:66395101-66400200:-1;chr9:66400201-67080000:0;chr9:67080001-67096200:-1;chr9:67096201-69132300:0;chr9:69132301-69158400:-1;chr9:69158401-78372000:0;chr9:78372001-78403500:-1;chr9:78403501-110528400:0;chrX:0-166650296:0;chrY:0-15902555:0 1700028P14Rik;4430402I18Rik;Apba1;BC021614;C030016D13Rik;Cdc37l1;Cep78;D19Bwg1357e;Dmrt1;Dmrt2;Dmrt3;E030010A14Rik;E030024N20Rik;Fam122a;Fam160b1;Fam189a2;Foxb2;Foxd4;Glis3;Gm10136;Gm6788;Gm815;Gna14;Gnaq;Gstp1;Gstp2;Hhex;Kcnv2;Lipa;Mlana;Pcsk5;Pgm5;Pip5k1b;Ppapdc2;Prune2;Psat1;Ptar1;Rfx3;Rorb;Slc1a1;Smarca2;Tjp2;Vldlr;Vps13a European Institute of Oncology (IEO), Department of Experimental Oncology, IFOM-IEO Campus, Via Adamello 16, 20139 Milan, Italy Hepatocellular carcinoma (HCC) is almost invariably associated with an underlying inflammatory state, whose direct contribution to the acquisition of critical genomic changes is unclear. Here we map acquired genomic alterations in human and mouse HCCs induced by defects in hepatocyte biliary transporters, which expose hepatocytes to bile salts and cause chronic inflammation that develops into cancer. In both human and mouse cancer genomes, we find few somatic point mutations with no impairment of cancer genes, but massive gene amplification and rearrangements. This genomic landscape differs from that of virus- and alcohol-associated liver cancer. Copy-number gains preferentially occur at late stages of cancer development and frequently target the MAPK signalling pathway, and in particular direct regulators of JNK. The pharmacological inhibition of JNK retards cancer progression in the mouse. Our study demonstrates that intrahepatic cholestasis leading to hepatocyte exposure to bile acids and inflammation promotes cancer through genomic modifications that can be distinguished from those determined by other aetiological factors. NCBI37/mm9 Yes NA CTDB0345 Research 26017449 Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, Nones K, Cowin P, Alsop K, Bailey PJ, Kassahn KS, Newell F, Quinn MC, Kazakoff S, Quek K, Wilhelm-Benartzi C, Curry E, Leong HS; Australian Ovarian Cancer Study Group, Hamilton A, Mileshkin L, Au-Yeung G, Kennedy C, Hung J, Chiew YE, Harnett P, Friedlander M, Quinn M, Pyman J, Cordner S, O'Brien P, Leditschke J, Young G, Strachan K, Waring P, Azar W, Mitchell C, Traficante N, Hendley J, Thorne H, Shackleton M, Miller DK, Arnau GM, Tothill RW, Holloway TP, Semple T, Harliwong I, Nourse C, Nourbakhsh E, Manning S, Idrisoglu S, Bruxner TJ, Christ AN, Poudel B, Holmes O, Anderson M, Leonard C, Lonie A, Hall N, Wood S, Taylor DF, Xu Q, Fink JL, Waddell N, Drapkin R, Stronach E, Gabra H, Brown R, Jewell A, Nagaraj SH, Markham E, Wilson PJ, Ellul J, McNally O, Doyle MA, Vedururu R, Stewart C, Lengyel E, Pearson JV, Waddell N, deFazio A, Grimmond SM, Bowtell DD Whole-genome characterization of chemoresistant ovarian cancer Nature 2015 May 15 Ovarian cancer Next Generation Sequencing Homo sapiens AOCS_097_ICGC_DBPC_20130205_074 Illumina Genome Network Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1. GRCh37/hg19 GSE65821 Yes NA CTDB0346 Research 26017449 Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, Nones K, Cowin P, Alsop K, Bailey PJ, Kassahn KS, Newell F, Quinn MC, Kazakoff S, Quek K, Wilhelm-Benartzi C, Curry E, Leong HS; Australian Ovarian Cancer Study Group, Hamilton A, Mileshkin L, Au-Yeung G, Kennedy C, Hung J, Chiew YE, Harnett P, Friedlander M, Quinn M, Pyman J, Cordner S, O'Brien P, Leditschke J, Young G, Strachan K, Waring P, Azar W, Mitchell C, Traficante N, Hendley J, Thorne H, Shackleton M, Miller DK, Arnau GM, Tothill RW, Holloway TP, Semple T, Harliwong I, Nourse C, Nourbakhsh E, Manning S, Idrisoglu S, Bruxner TJ, Christ AN, Poudel B, Holmes O, Anderson M, Leonard C, Lonie A, Hall N, Wood S, Taylor DF, Xu Q, Fink JL, Waddell N, Drapkin R, Stronach E, Gabra H, Brown R, Jewell A, Nagaraj SH, Markham E, Wilson PJ, Ellul J, McNally O, Doyle MA, Vedururu R, Stewart C, Lengyel E, Pearson JV, Waddell N, deFazio A, Grimmond SM, Bowtell DD Whole-genome characterization of chemoresistant ovarian cancer Nature 2015 May 8 Ovarian cancer Next Generation Sequencing Homo sapiens AOCS_132_ICGC_DBPC_20130205_120 Illumina Genome Network Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1. GRCh37/hg19 GSE65821 Yes NA CTDB0347 Research 26017449 Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, Nones K, Cowin P, Alsop K, Bailey PJ, Kassahn KS, Newell F, Quinn MC, Kazakoff S, Quek K, Wilhelm-Benartzi C, Curry E, Leong HS; Australian Ovarian Cancer Study Group, Hamilton A, Mileshkin L, Au-Yeung G, Kennedy C, Hung J, Chiew YE, Harnett P, Friedlander M, Quinn M, Pyman J, Cordner S, O'Brien P, Leditschke J, Young G, Strachan K, Waring P, Azar W, Mitchell C, Traficante N, Hendley J, Thorne H, Shackleton M, Miller DK, Arnau GM, Tothill RW, Holloway TP, Semple T, Harliwong I, Nourse C, Nourbakhsh E, Manning S, Idrisoglu S, Bruxner TJ, Christ AN, Poudel B, Holmes O, Anderson M, Leonard C, Lonie A, Hall N, Wood S, Taylor DF, Xu Q, Fink JL, Waddell N, Drapkin R, Stronach E, Gabra H, Brown R, Jewell A, Nagaraj SH, Markham E, Wilson PJ, Ellul J, McNally O, Doyle MA, Vedururu R, Stewart C, Lengyel E, Pearson JV, Waddell N, deFazio A, Grimmond SM, Bowtell DD Whole-genome characterization of chemoresistant ovarian cancer Nature 2015 May 13 Ovarian cancer Next Generation Sequencing Homo sapiens AOCS_093_ICGC_DBPC_20130205_064 Illumina Genome Network BRCA2 Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1. GRCh37/hg19 GSE65821 Yes NA CTDB0348 Research 26017449 Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, Nones K, Cowin P, Alsop K, Bailey PJ, Kassahn KS, Newell F, Quinn MC, Kazakoff S, Quek K, Wilhelm-Benartzi C, Curry E, Leong HS; Australian Ovarian Cancer Study Group, Hamilton A, Mileshkin L, Au-Yeung G, Kennedy C, Hung J, Chiew YE, Harnett P, Friedlander M, Quinn M, Pyman J, Cordner S, O'Brien P, Leditschke J, Young G, Strachan K, Waring P, Azar W, Mitchell C, Traficante N, Hendley J, Thorne H, Shackleton M, Miller DK, Arnau GM, Tothill RW, Holloway TP, Semple T, Harliwong I, Nourse C, Nourbakhsh E, Manning S, Idrisoglu S, Bruxner TJ, Christ AN, Poudel B, Holmes O, Anderson M, Leonard C, Lonie A, Hall N, Wood S, Taylor DF, Xu Q, Fink JL, Waddell N, Drapkin R, Stronach E, Gabra H, Brown R, Jewell A, Nagaraj SH, Markham E, Wilson PJ, Ellul J, McNally O, Doyle MA, Vedururu R, Stewart C, Lengyel E, Pearson JV, Waddell N, deFazio A, Grimmond SM, Bowtell DD Whole-genome characterization of chemoresistant ovarian cancer Nature 2015 May 6 Ovarian cancer Next Generation Sequencing Homo sapiens AOCS_160_ICGC_DBDE_20130904_014 Illumina Genome Network Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1. GRCh37/hg19 GSE65821 Yes NA CTDB0349 Research 26017449 Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, Nones K, Cowin P, Alsop K, Bailey PJ, Kassahn KS, Newell F, Quinn MC, Kazakoff S, Quek K, Wilhelm-Benartzi C, Curry E, Leong HS; Australian Ovarian Cancer Study Group, Hamilton A, Mileshkin L, Au-Yeung G, Kennedy C, Hung J, Chiew YE, Harnett P, Friedlander M, Quinn M, Pyman J, Cordner S, O'Brien P, Leditschke J, Young G, Strachan K, Waring P, Azar W, Mitchell C, Traficante N, Hendley J, Thorne H, Shackleton M, Miller DK, Arnau GM, Tothill RW, Holloway TP, Semple T, Harliwong I, Nourse C, Nourbakhsh E, Manning S, Idrisoglu S, Bruxner TJ, Christ AN, Poudel B, Holmes O, Anderson M, Leonard C, Lonie A, Hall N, Wood S, Taylor DF, Xu Q, Fink JL, Waddell N, Drapkin R, Stronach E, Gabra H, Brown R, Jewell A, Nagaraj SH, Markham E, Wilson PJ, Ellul J, McNally O, Doyle MA, Vedururu R, Stewart C, Lengyel E, Pearson JV, Waddell N, deFazio A, Grimmond SM, Bowtell DD Whole-genome characterization of chemoresistant ovarian cancer Nature 2015 May 4 Ovarian cancer Next Generation Sequencing Homo sapiens AOCS_034_ICGC_DBPC_20130205_009 Illumina Genome Network Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1. GRCh37/hg19 GSE65821 Yes NA CTDB0350 Research 26017449 Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, Nones K, Cowin P, Alsop K, Bailey PJ, Kassahn KS, Newell F, Quinn MC, Kazakoff S, Quek K, Wilhelm-Benartzi C, Curry E, Leong HS; Australian Ovarian Cancer Study Group, Hamilton A, Mileshkin L, Au-Yeung G, Kennedy C, Hung J, Chiew YE, Harnett P, Friedlander M, Quinn M, Pyman J, Cordner S, O'Brien P, Leditschke J, Young G, Strachan K, Waring P, Azar W, Mitchell C, Traficante N, Hendley J, Thorne H, Shackleton M, Miller DK, Arnau GM, Tothill RW, Holloway TP, Semple T, Harliwong I, Nourse C, Nourbakhsh E, Manning S, Idrisoglu S, Bruxner TJ, Christ AN, Poudel B, Holmes O, Anderson M, Leonard C, Lonie A, Hall N, Wood S, Taylor DF, Xu Q, Fink JL, Waddell N, Drapkin R, Stronach E, Gabra H, Brown R, Jewell A, Nagaraj SH, Markham E, Wilson PJ, Ellul J, McNally O, Doyle MA, Vedururu R, Stewart C, Lengyel E, Pearson JV, Waddell N, deFazio A, Grimmond SM, Bowtell DD Whole-genome characterization of chemoresistant ovarian cancer Nature 2015 May 12 Ovarian cancer Next Generation Sequencing Homo sapiens AOCS_152_ICGC_DBPC_20130205_174 Illumina Genome Network Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1. GRCh37/hg19 GSE65821 Yes NA CTDB0351 Research 25496518 Reimann E, Koks S, Ho XD, Maasalu K, Martson A Whole exome sequencing of a single osteosarcoma case--integrative analysis with whole transcriptome RNA-seq data Human Genomics 2014 Dec 8 Osteosarcoma Next Generation Sequencing Homo sapiens case 1 SOLiD 5500xl chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-77755834:0;chr13:77755835-77756057:1;chr13:77756058-77759236:0;chr13:77759237-77759512:1;chr13:77759513-77760004:0;chr13:77760005-77760198:1;chr13:77760199-77763084:0;chr13:77763085-77763182:1;chr13:77763183-77764385:0;chr13:77764386-77764470:1;chr13:77764471-77765812:0;chr13:77765813-77765948:1;chr13:77765949-77768286:0;chr13:77768287-77768379:1;chr13:77768380-77779389:0;chr13:77779390-77779518:1;chr13:77779519-77779606:0;chr13:77779607-77779733:1;chr13:77779734-77780786:0;chr13:77780787-77780960:1;chr13:77780961-77785300:0;chr13:77785301-77785455:1;chr13:77785456-77786089:0;chr13:77786090-77786295:1;chr13:77786296-77791973:0;chr13:77791974-77792092:1;chr13:77792093-77798584:0;chr13:77798585-77798667:1;chr13:77798668-77799568:0;chr13:77799569-77799689:1;chr13:77799690-77807289:0;chr13:77807290-77807398:1;chr13:77807399-77817192:0;chr13:77817193-77817295:1;chr13:77817296-77817939:0;chr13:77817940-77818086:1;chr13:77818087-77825284:0;chr13:77825285-77825490:1;chr13:77825491-77831804:0;chr13:77831805-77831964:1;chr13:77831965-77834561:0;chr13:77834562-77834727:1;chr13:77834728-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-7058570:0;chr19:10102679-10102724:-1;chr19:10102725-10103501:0;chr19:10103502-10103556:-1;chr19:10103557-10104054:0;chr19:10104055-10104109:-1;chr19:10104110-10104293:0;chr19:10104294-10104348:-1;chr19:10104349-10104427:0;chr19:10104428-10104482:-1;chr19:10104483-10106238:0;chr19:10106239-10106293:-1;chr19:10106294-10106740:0;chr19:10106741-10106795:-1;chr19:10106796-10106880:0;chr19:10106881-10106938:-1;chr19:10106939-10107107:0;chr19:10107108-10107192:-1;chr19:10107193-10108045:0;chr19:10108046-10108109:-1;chr19:10108110-10108658:0;chr19:10108659-10108701:-1;chr19:10108702-10108776:0;chr19:10108777-10108825:-1;chr19:10108826-10112198:0;chr19:10112199-10112346:-1;chr19:10112347-10112442:0;chr19:10112443-10112557:-1;chr19:10112558-10114239:0;chr19:10114240-10114390:-1;chr19:10114391-10114715:0;chr19:10114716-10114821:-1;chr19:10114822-10116232:0;chr19:10116233-10116390:-1;chr19:10116391-10120972:0;chr19:10120973-10121147:-1;chr19:10121148-10127731:0;chr19:10127732-10127891:-1;chr19:10127892-10129405:0;chr19:10129406-10129586:-1;chr19:10129587-12910989:0;chr19:101971714-101971828:-1;chr19:101971829-101999993:0;chr19:101999994-102000164:-1;chr19:12910990-12911113:-1;chr19:12911114-12911425:0;chr19:12911426-12911883:-1;chr19:12911729-12911883:-1;chr19:12911884-12911971:0;chr19:12911972-12912084:-1;chr19:12912085-12912552:0;chr19:12912553-12912694:-1;chr19:12912695-12918018:0;chr19:12918019-12918143:-1;chr19:12918144-12918231:0;chr19:12918232-12918320:-1;chr19:12918321-12920883:0;chr19:12920884-12921022:-1;chr19:12921023-12921129:0;chr19:12921130-12921218:-1;chr19:12921219-12923895:0;chr19:12923896-12924020:-1;chr19:12924021-12924140:0;chr19:12924141-12924462:-1;chr19:12924463-12937587:0;chr19:12937588-12937685:-1;chr19:12937686-12945597:0;chr19:12945598-12945660:-1;chr19:12945661-12949257:0;chr19:12949258-12949469:-1;chr19:12949470-12951258:0;chr19:12951259-12951348:-1;chr19:12951349-12951803:0;chr19:12951804-12951880:-1;chr19:12951881-12954341:0;chr19:12954342-12954421:-1;chr19:12954422-12958102:0;chr19:12958103-12958264:-1;chr19:12958265-12958424:0;chr19:12958425-12958501:-1;chr19:12958502-12958660:0;chr19:12958661-12958871:-1;chr19:12958872-12962746:0;chr19:12962747-12962849:-1;chr19:12962850-12962927:0;chr19:12962928-12963061:-1;chr19:12963062-12963140:0;chr19:12963141-12963209:-1;chr19:12963210-12969174:0;chr19:12969175-12969255:-1;chr19:12969256-12969343:0;chr19:12969344-12969553:-1;chr19:12969554-12975621:0;chr19:12975622-12975761:-1;chr19:12975762-12975858:0;chr19:12975859-12975992:-1;chr19:12975993-12976128:0;chr19:12976129-12976295:-1;chr19:12976296-12976529:0;chr19:12976530-12976632:-1;chr19:12976633-12976792:0;chr19:12976793-12976916:-1;chr19:12976917-12977465:0;chr19:12977466-12977576:-1;chr19:12977577-12978286:0;chr19:12978287-12978466:-1;chr19:12978467-12979455:0;chr19:12979456-12979663:-1;chr19:12979664-12979878:0;chr19:12979879-12980109:-1;chr19:12980110-12981636:0;chr19:12981637-12981760:-1;chr19:12981761-12981848:0;chr19:12981849-12981986:-1;chr19:12981987-12984136:0;chr19:12984137-12984325:-1;chr19:12984326-12989482:0;chr19:12989483-12989648:-1;chr19:12989649-12991614:0;chr19:12991615-12991694:-1;chr19:12991695-12992102:0;chr19:12992103-12992335:-1;chr19:12992336-12997866:0;chr19:12997867-12998017:-1;chr19:12998018-13002299:0;chr19:13002300-13002336:-1;chr19:13002337-13002643:0;chr19:13002644-13002788:-1;chr19:13002789-13002928:0;chr19:13002929-13002992:-1;chr19:13002993-13004295:0;chr19:13004296-13004467:-1;chr19:13004468-13006804:0;chr19:13006805-13006935:-1;chr19:13006936-13007017:0;chr19:13007018-13007235:-1;chr19:13007236-13007722:0;chr19:13007723-13007827:-1;chr19:13007828-13008115:0;chr19:13008116-13008242:-1;chr19:13008243-13008515:0;chr19:13008516-13008677:-1;chr19:13008678-13010280:0;chr19:13010281-13010783:-1;chr19:13010513-13010783:-1;chr19:13010784-13010816:0;chr19:13010817-13010934:-1;chr19:13010935-13011272:0;chr19:13011273-13011462:-1;chr19:13011463-13015304:0;chr19:13015305-13015480:-1;chr19:13015481-13029034:0;chr19:13029035-13029151:-1;chr19:13029152-13030055:0;chr19:13030056-13030086:-1;chr19:13030087-13034963:0;chr19:13034964-13035079:-1;chr19:13035080-13035261:0;chr19:13035262-13035340:-1;chr19:13035341-13035451:0;chr19:13035452-13035621:-1;chr19:13035622-13035716:0;chr19:13035717-13035817:-1;chr19:13035818-13035902:0;chr19:13035903-13035988:-1;chr19:13035989-13039154:0;chr19:13039155-13039271:-1;chr19:13039272-13039347:0;chr19:13039348-13039477:-1;chr19:13039478-13039567:0;chr19:13039568-13039661:-1;chr19:13039662-13041035:0;chr19:13041036-13041155:-1;chr19:13041156-13041241:0;chr19:13041242-13041341:-1;chr19:13041342-13041424:0;chr19:13041425-13041563:-1;chr19:13041564-13044362:0;chr19:13044363-13044558:-1;chr19:13044559-13050240:0;chr19:13050241-13050445:-1;chr19:13050446-13050865:0;chr19:13050866-13050961:-1;chr19:13050962-13051055:0;chr19:13051056-13051266:-1;chr19:13051267-13051353:0;chr19:13051354-13051468:-1;chr19:13051469-13051556:0;chr19:13051557-13051701:-1;chr19:13051702-13054349:0;chr19:13054350-13054443:-1;chr19:13054444-13056626:0;chr19:13056627-13056834:-1;chr19:13056835-13058660:0;chr19:13058661-13058823:-1;chr19:13058824-13058989:0;chr19:13058990-13059172:-1;chr19:13059173-13059309:0;chr19:13059310-13059366:-1;chr19:13059367-13059893:0;chr19:13059894-13059973:-1;chr19:13059974-13060087:0;chr19:13060088-13060222:-1;chr19:13060091-13060222:-1;chr19:13060223-13063501:0;chr19:13063502-13063667:-1;chr19:13063668-13064970:0;chr19:13064971-13065340:-1;chr19:13065341-13067675:0;chr19:13067676-13068050:-1;chr19:13068051-13106582:0;chr19:13106583-13106678:-1;chr19:13106679-13135833:0;chr19:13135834-13136366:-1;chr19:13136367-13183859:0;chr19:13183860-13183923:-1;chr19:13183924-13184234:0;chr19:13184235-13184310:-1;chr19:13184311-13184718:0;chr19:13184719-13184840:-1;chr19:13184841-13186347:0;chr19:13186348-13186485:-1;chr19:13186486-13189425:0;chr19:13189426-13189549:-1;chr19:13189550-13192492:0;chr19:13192493-13192669:-1;chr19:13192670-13201111:0;chr19:13201112-13201204:-1;chr19:13201205-13211469:0;chr19:13211470-13211562:-1;chr19:13211563-13213343:0;chr19:13213344-13213974:-1;chr19:13213975-13216079:0;chr19:13216080-13216210:-1;chr19:13216211-13216299:0;chr19:13216300-13216420:-1;chr19:13216421-13218386:0;chr19:13218387-13218464:-1;chr19:13218465-13218563:0;chr19:13218564-13218673:-1;chr19:13218674-13220193:0;chr19:13220194-13220280:-1;chr19:13220281-13220581:0;chr19:13220582-13220652:-1;chr19:13220653-13220727:0;chr19:13220728-13220815:-1;chr19:13220816-13220970:0;chr19:13220971-13221120:-1;chr19:13221121-13223517:0;chr19:13223518-13223631:-1;chr19:13223632-13223708:0;chr19:13223709-13223825:-1;chr19:13223826-13226091:0;chr19:13226092-13226280:-1;chr19:13226281-13226438:0;chr19:13226439-13226582:-1;chr19:13226583-13226809:0;chr19:13226810-13226866:-1;chr19:13226867-13226958:0;chr19:13226959-13227245:-1;chr19:13227246-13229100:0;chr19:13229101-13229268:-1;chr19:13229269-13246012:0;chr19:13246013-13246967:-1;chr19:13246968-13247044:0;chr19:13247045-13247219:-1;chr19:13247220-13248083:0;chr19:13248084-13248190:-1;chr19:13248191-13248290:0;chr19:13248291-13248389:-1;chr19:13248390-13255222:0;chr19:13255223-13255300:-1;chr19:13255301-13255389:0;chr19:13255390-13255485:-1;chr19:13255486-13255576:0;chr19:13255577-13255684:-1;chr19:13255685-13256100:0;chr19:13256101-13256209:-1;chr19:13256210-13259841:0;chr19:13259842-13259905:-1;chr19:13259906-13260311:0;chr19:13260312-13260407:-1;chr19:13260408-13260540:0;chr19:13260541-13260711:-1;chr19:13260712-13260951:0;chr19:13260952-13260987:-1;chr19:13260988-13317254:0;chr19:13317255-13318862:-1;chr19:13318863-13319568:0;chr19:13319569-13319823:-1;chr19:13319824-13320124:0;chr19:13320125-13320312:-1;chr19:13320313-13321429:0;chr19:13321430-13321466:-1;chr19:13321467-13322915:0;chr19:13322916-13323030:-1;chr19:13323031-13323196:0;chr19:13323197-13323336:-1;chr19:13323337-13325045:0;chr19:13325046-13325147:-1;chr19:13325148-13325313:0;chr19:13325314-13325422:-1;chr19:13325423-13335479:0;chr19:13335480-13335586:-1;chr19:13335587-13338243:0;chr19:13338244-13338341:-1;chr19:13338342-13339511:0;chr19:13339512-13339609:-1;chr19:13339610-13340894:0;chr19:13340895-13341023:-1;chr19:13341024-13342522:0;chr19:13342523-13342674:-1;chr19:13342675-13345733:0;chr19:13345734-13345850:-1;chr19:13345851-13346021:0;chr19:13346022-13346088:-1;chr19:13346089-13346426:0;chr19:13346427-13346545:-1;chr19:13346546-13355994:0;chr19:13355995-13356079:-1;chr19:13356080-13363803:0;chr19:13363804-13363915:-1;chr19:13363916-13365907:0;chr19:13365908-13366073:-1;chr19:13366074-13368162:0;chr19:13368163-13368365:-1;chr19:13368366-13370376:0;chr19:13370377-13370515:-1;chr19:13370516-13372262:0;chr19:13372263-13372424:-1;chr19:13372425-13373546:0;chr19:13373547-13373647:-1;chr19:13373648-13386662:0;chr19:13386663-13386770:-1;chr19:13386771-13387881:0;chr19:13387882-13387942:-1;chr19:13387943-13394079:0;chr19:13394080-13394210:-1;chr19:13394211-13395880:0;chr19:13395881-13396020:-1;chr19:13396021-13397315:0;chr19:13397316-13397780:-1;chr19:13397781-13411362:0;chr19:13411363-13411470:-1;chr19:13411471-13414349:0;chr19:13414350-13414427:-1;chr19:13414359-13414427:-1;chr19:13414428-13414579:0;chr19:13414580-13414698:-1;chr19:13414699-13418594:0;chr19:13418595-13418668:-1;chr19:13418669-13418932:0;chr19:13418933-13419065:-1;chr19:13419066-13419228:0;chr19:13419229-13419342:-1;chr19:13419343-13423481:0;chr19:13423482-13423595:-1;chr19:13423596-13427924:0;chr19:13427925-13428135:-1;chr19:13428136-13441056:0;chr19:13441057-13441150:-1;chr19:13441151-13443681:0;chr19:13443682-13443739:-1;chr19:13443740-13445190:0;chr19:13445191-13445307:-1;chr19:13445308-13446618:0;chr19:13446619-13446723:-1;chr19:13446724-13470418:0;chr19:13470419-13470613:-1;chr19:13470614-13476129:0;chr19:13476130-13476283:-1;chr19:13476284-13482500:0;chr19:13482501-13482593:-1;chr19:13482594-13563688:0;chr19:13563689-13563829:-1;chr19:13563830-13565919:0;chr19:13565920-13566026:-1;chr19:13566027-13862420:0;chr19:13862421-13862625:-1;chr19:13862626-13865101:0;chr19:13865102-13865156:-1;chr19:13865157-14104335:0;chr19:14104336-14104707:-1;chr19:14104708-14116913:0;chr19:14116914-14117134:-1;chr19:14117135-14139015:0;chr19:14139016-14139206:-1;chr19:14139207-14141520:0;chr19:14141521-14141783:-1;chr19:14141784-14142550:0;chr19:14142551-14142784:-1;chr19:14142785-14143196:0;chr19:14143197-14143315:-1;chr19:14143316-14150318:0;chr19:14150319-14150477:-1;chr19:14150478-14150563:0;chr19:14150564-14150722:-1;chr19:14150723-14153263:0;chr19:14153264-14153424:-1;chr19:14153425-14153526:0;chr19:14153527-14153601:-1;chr19:14153602-14156964:0;chr19:14156965-14157149:-1;chr19:14157150-14157240:0;chr19:14157241-14157430:-1;chr19:14157431-14159791:0;chr19:14159792-14159894:-1;chr19:14159895-14159966:0;chr19:14159967-14160126:-1;chr19:14160127-14161568:0;chr19:14161569-14161695:-1;chr19:14161696-14162417:0;chr19:14162418-14162512:-1;chr19:14162513-14162690:0;chr19:14162691-14162785:-1;chr19:14162786-14166190:0;chr19:14166191-14166237:-1;chr19:14166238-14167239:0;chr19:14167240-14167325:-1;chr19:14167326-14167472:0;chr19:14167473-14167616:-1;chr19:14167617-14168161:0;chr19:14168162-14168243:-1;chr19:14168244-14169925:0;chr19:14169926-14169971:-1;chr19:14169972-14199227:0;chr19:14199228-14199387:-1;chr19:14199388-14199481:0;chr19:14199482-14199593:-1;chr19:14199594-14199878:0;chr19:14199879-14200174:-1;chr19:14200175-14200595:0;chr19:14200596-14201232:-1;chr19:14201233-14208171:0;chr19:14208172-14208295:-1;chr19:14208296-14208389:0;chr19:14208390-14208486:-1;chr19:14208487-14208574:0;chr19:14208575-14208702:-1;chr19:14208703-14211636:0;chr19:14211637-14211720:-1;chr19:14211721-14213626:0;chr19:14213627-14213726:-1;chr19:14213727-14217570:0;chr19:14217571-14217700:-1;chr19:14217701-14218158:0;chr19:14218159-14218221:-1;chr19:14218222-14224944:0;chr19:14224945-14224992:-1;chr19:14224993-14228312:0;chr19:14228313-14228559:-1;chr19:14228560-14262943:0;chr19:14262944-14262962:-1;chr19:14262963-14263119:0;chr19:14263120-14263249:-1;chr19:14263250-14263327:0;chr19:14263328-14263425:-1;chr19:14263426-14263594:0;chr19:14263595-14263724:-1;chr19:14263725-14266169:0;chr19:14266170-14266339:-1;chr19:14266340-14267468:0;chr19:14267469-14267536:-1;chr19:14267537-14267735:0;chr19:14267736-14267957:-1;chr19:14267958-14268061:0;chr19:14268062-14268272:-1;chr19:14268273-14268692:0;chr19:14268693-14268864:-1;chr19:14268865-14269148:0;chr19:14269149-14269364:-1;chr19:14269365-14269900:0;chr19:14269901-14270027:-1;chr19:14270028-14270545:0;chr19:14270546-14270585:-1;chr19:14270586-14271403:0;chr19:14271404-14271508:-1;chr19:14271509-14273416:0;chr19:14273417-14274218:-1;chr19:14274219-14277826:0;chr19:14277827-14277842:-1;chr19:14277843-14281492:0;chr19:14281493-14281603:-1;chr19:14281604-14288341:0;chr19:14288342-14288556:-1;chr19:14288557-14316795:0;chr19:14316796-14316997:-1;chr19:14316998-14499260:0;chr19:14499261-14499312:-1;chr19:14499313-31545751:0;chr19:31545752-31545819:-1;chr19:31545820-31551398:0;chr19:31551399-31551539:-1;chr19:31551540-77376610:0;chr19:7058571-7058645:-1;chr19:7058646-7069469:0;chr19:7069470-7069772:-1;chr19:7069773-7070571:0;chr19:7070572-7070664:-1;chr19:7070665-7075005:0;chr19:7075006-7075116:-1;chr19:7075117-7075664:0;chr19:7075665-7075754:-1;chr19:7075686-7075754:-1;chr19:7075755-7076390:0;chr19:7076391-7076518:-1;chr19:7076519-7081369:0;chr19:7081370-7081466:-1;chr19:7081467-7081979:0;chr19:7081980-7082063:-1;chr19:7082064-7119458:0;chr19:7119459-7119594:-1;chr19:7119595-7120629:0;chr19:7120630-7120760:-1;chr19:7120761-7122623:0;chr19:7122624-7122784:-1;chr19:7122785-7122888:0;chr19:7122889-7123000:-1;chr19:7123001-7125292:0;chr19:7125293-7125538:-1;chr19:7125539-7126593:0;chr19:7126594-7126662:-1;chr19:7126663-7128861:0;chr19:7128862-7128965:-1;chr19:7128966-7132167:0;chr19:7132168-7132328:-1;chr19:7132329-7141686:0;chr19:7141687-7141827:-1;chr19:7141828-7142825:0;chr19:7142826-7143101:-1;chr19:7143102-7150506:0;chr19:7150507-7150543:-1;chr19:7150544-7152735:0;chr19:7152736-7152938:-1;chr19:7152939-7163041:0;chr19:7163042-7163210:-1;chr19:7163211-7166163:0;chr19:7166164-7166415:-1;chr19:7166416-7167977:0;chr19:7167978-7168105:-1;chr19:7168106-7170546:0;chr19:7170547-7170762:-1;chr19:7170763-7172299:0;chr19:7172300-7172445:-1;chr19:7172446-7174592:0;chr19:7174593-7174742:-1;chr19:7174743-7184325:0;chr19:7184326-7184648:-1;chr19:7184649-7267354:0;chr19:7267355-7267907:-1;chr19:7267908-7293801:0;chr19:7293802-7294011:-1;chr19:7294012-7459997:0;chr19:7459998-7460133:-1;chr19:7459998-7460133:-1;chr19:7460134-7504572:0;chr19:7504573-7505368:-1;chr19:7505229-7505368:-1;chr19:7505369-7506537:0;chr19:7506538-7506651:-1;chr19:7506652-7506796:0;chr19:7506797-7506938:-1;chr19:7506939-7509088:0;chr19:7509089-7509340:-1;chr19:7509341-7511927:0;chr19:7511928-7512054:-1;chr19:7512055-7516033:0;chr19:7516034-7516152:-1;chr19:7516153-7518351:0;chr19:7518352-7518601:-1;chr19:7518602-7521211:0;chr19:7521212-7521289:-1;chr19:7521290-7523396:0;chr19:7523397-7523576:-1;chr19:7523577-7524787:0;chr19:7524788-7524880:-1;chr19:7524881-7527036:0;chr19:7527037-7527220:-1;chr19:7527221-7529444:0;chr19:7529445-7529576:-1;chr19:7529577-7531955:0;chr19:7531956-7532004:-1;chr19:7532005-7532098:0;chr19:7532099-7532570:-1;chr19:7532571-7534788:0;chr19:7534789-7534915:-1;chr19:7534916-7543198:0;chr19:7543199-7543262:-1;chr19:7543263-7546917:0;chr19:7546918-7547097:-1;chr19:7547098-7550722:0;chr19:7550723-7550912:-1;chr19:7550913-7553835:0;chr19:7553836-7553924:-1;chr19:7553925-7562443:0;chr19:7562444-7562568:-1;chr19:7562569-7569005:0;chr19:7569006-7569110:-1;chr19:7569111-7569195:0;chr19:7569196-7569297:-1;chr19:7569298-7570208:0;chr19:7570209-7570322:-1;chr19:7570323-7570401:0;chr19:7570402-7570512:-1;chr19:7570513-7570848:0;chr19:7570849-7571051:-1;chr19:7571052-7571940:0;chr19:7571941-7572027:-1;chr19:7572028-7573090:0;chr19:7573091-7573336:-1;chr19:7573337-7589845:0;chr19:7589846-7590052:-1;chr19:7590053-7591323:0;chr19:7591324-7591492:-1;chr19:7591493-7591645:0;chr19:7591646-7591812:-1;chr19:7591813-7592404:0;chr19:7592405-7592514:-1;chr19:7592515-7592748:0;chr19:7592749-7592846:-1;chr19:7592847-7593042:0;chr19:7593043-7593143:-1;chr19:7593144-7593481:0;chr19:7593482-7593589:-1;chr19:7593590-7593705:0;chr19:7593706-7593856:-1;chr19:7593857-7593985:0;chr19:7593986-7594088:-1;chr19:7594089-7594474:0;chr19:7594475-7594598:-1;chr19:7594599-7595170:0;chr19:7595171-7595387:-1;chr19:7595388-7734201:0;chr19:7734202-7734330:-1;chr19:7734211-7734330:-1;chr19:7734331-7734705:0;chr19:7734706-7734784:-1;chr19:7734785-7741941:0;chr19:77376611-77376724:-1;chr19:77376725-101971713:0;chr19:7741942-7742061:-1;chr19:7742062-7742521:0;chr19:7742522-7742612:-1;chr19:7742613-7742988:0;chr19:7742989-7743127:-1;chr19:7743128-7743234:0;chr19:7743235-7743286:-1;chr19:7743287-7755043:0;chr19:7755044-7755151:-1;chr19:7755152-7755290:0;chr19:7755291-7755443:-1;chr19:7755444-7761709:0;chr19:7761710-7761800:-1;chr19:7761801-7761897:0;chr19:7761898-7761961:-1;chr19:7761962-7762120:0;chr19:7762121-7762184:-1;chr19:7762185-7762411:0;chr19:7762412-7762475:-1;chr19:7762476-7763240:0;chr19:7763241-7763295:-1;chr19:7763296-7763625:0;chr19:7763626-7763740:-1;chr19:7763741-7764261:0;chr19:7764262-7764365:-1;chr19:7764366-7764623:0;chr19:7764624-7764731:-1;chr19:7764732-8668610:0;chr19:8668611-8668768:-1;chr19:8668769-8670506:0;chr19:8670507-8670694:-1;chr19:8670695-8673014:0;chr19:8673015-8673130:-1;chr19:8673131-8675527:0;chr19:8675528-8675588:-1;chr19:8675589-8841389:0;chr19:8841390-8842335:-1;chr19:8842336-8923235:0;chr19:8923236-8923319:-1;chr19:8923320-8923801:0;chr19:8923802-8923898:-1;chr19:8923899-8931854:0;chr19:8931855-8931982:-1;chr19:8931983-8932677:0;chr19:8932678-8932767:-1;chr19:8932768-8953267:0;chr19:8953268-8954016:-1;chr19:8954017-8959518:0;chr19:8959519-8959706:-1;chr19:8959707-8961950:0;chr19:8961951-8962031:-1;chr19:8962032-8962352:0;chr19:8962353-8962395:-1;chr19:8962396-8966648:0;chr19:8966649-8966816:-1;chr19:8966817-8968878:0;chr19:8968879-8968947:-1;chr19:8968948-8969274:0;chr19:8969275-8969427:-1;chr19:8969428-8971674:0;chr19:8971675-8971824:-1;chr19:8971825-8973547:0;chr19:8973548-8973616:-1;chr19:8973617-8973970:0;chr19:8973971-8974102:-1;chr19:8974103-8976258:0;chr19:8976259-8976432:-1;chr19:8976433-8976579:0;chr19:8976580-8976648:-1;chr19:8976649-8976737:0;chr19:8976738-8976860:-1;chr19:8976861-8977638:0;chr19:8977639-8977690:-1;chr19:8977691-8979215:0;chr19:8979216-8979252:-1;chr19:8979253-8982155:0;chr19:8982156-8982329:-1;chr19:8982330-8987043:0;chr19:8987044-8987112:-1;chr19:8987113-8987208:0;chr19:8987209-8987334:-1;chr19:8987335-8993005:0;chr19:8993006-8993042:-1;chr19:8993043-8993371:0;chr19:8993372-8993545:-1;chr19:8993546-8994140:0;chr19:8994141-8994209:-1;chr19:8994210-8994415:0;chr19:8994416-8994538:-1;chr19:8994539-8995633:0;chr19:8995634-8995700:-1;chr19:8995701-8995952:0;chr19:8995953-8995989:-1;chr19:8995990-8996319:0;chr19:8996320-8996493:-1;chr19:8996494-8997116:0;chr19:8997117-8997185:-1;chr19:8997186-8997410:0;chr19:8997411-8997536:-1;chr19:8997537-8998696:0;chr19:8998697-8998763:-1;chr19:8998764-8999023:0;chr19:8999024-8999060:-1;chr19:8999061-8999390:0;chr19:8999391-8999564:-1;chr19:8999565-9000145:0;chr19:9000146-9000214:-1;chr19:9000215-9000440:0;chr19:9000441-9000566:-1;chr19:9000567-9001829:0;chr19:9001830-9001896:-1;chr19:9001897-9002151:0;chr19:9002152-9002188:-1;chr19:9002189-9002499:0;chr19:9002500-9002673:-1;chr19:9002674-9003291:0;chr19:9003292-9003360:-1;chr19:9003361-9003564:0;chr19:9003565-9003690:-1;chr19:9003691-9004867:0;chr19:9004868-9004934:-1;chr19:9004935-9005192:0;chr19:9005193-9005229:-1;chr19:9005230-9005557:0;chr19:9005558-9005731:-1;chr19:9005732-9006342:0;chr19:9006343-9006411:-1;chr19:9006412-9006640:0;chr19:9006641-9006766:-1;chr19:9006767-9007485:0;chr19:9007486-9007552:-1;chr19:9007553-9007807:0;chr19:9007808-9007844:-1;chr19:9007845-9008171:0;chr19:9008172-9008345:-1;chr19:9008346-9009265:0;chr19:9009266-9009334:-1;chr19:9009335-9009586:0;chr19:9009587-9009712:-1;chr19:9009713-9010646:0;chr19:9010647-9010713:-1;chr19:9010714-9010969:0;chr19:9010970-9011006:-1;chr19:9011007-9011320:0;chr19:9011321-9011494:-1;chr19:9011495-9012466:0;chr19:9012467-9012535:-1;chr19:9012536-9012772:0;chr19:9012773-9012898:-1;chr19:9012899-9013843:0;chr19:9013844-9013910:-1;chr19:9013911-9014167:0;chr19:9014168-9014204:-1;chr19:9014205-9014530:0;chr19:9014531-9014704:-1;chr19:9014705-9015316:0;chr19:9015317-9015385:-1;chr19:9015386-9015619:0;chr19:9015620-9015745:-1;chr19:9015746-9016658:0;chr19:9016659-9016722:-1;chr19:9016723-9016979:0;chr19:9016980-9017016:-1;chr19:9017017-9017344:0;chr19:9017345-9017518:-1;chr19:9017519-9018131:0;chr19:9018132-9018200:-1;chr19:9018201-9018435:0;chr19:9018436-9018561:-1;chr19:9018562-9019273:0;chr19:9019274-9019340:-1;chr19:9019341-9019598:0;chr19:9019599-9019635:-1;chr19:9019636-9019983:0;chr19:9019984-9020157:-1;chr19:9020158-9020763:0;chr19:9020764-9020832:-1;chr19:9020833-9021052:0;chr19:9021053-9021184:-1;chr19:9021185-9024132:0;chr19:9024133-9024199:-1;chr19:9024200-9024459:0;chr19:9024460-9024496:-1;chr19:9024497-9024824:0;chr19:9024825-9024998:-1;chr19:9024999-9025589:0;chr19:9025590-9025658:-1;chr19:9025659-9026189:0;chr19:9026190-9026315:-1;chr19:9026316-9027214:0;chr19:9027215-9027281:-1;chr19:9027282-9027538:0;chr19:9027539-9027575:-1;chr19:9027576-9028222:0;chr19:9028223-9028396:-1;chr19:9028397-9033229:0;chr19:9033230-9033298:-1;chr19:9033299-9033608:0;chr19:9033609-9033737:-1;chr19:9033738-9038075:0;chr19:9038076-9038136:-1;chr19:9038137-9038378:0;chr19:9038379-9038415:-1;chr19:9038416-9043424:0;chr19:9043425-9043461:-1;chr19:9043462-9045562:0;chr19:9045563-9050243:-1;chr19:9050244-9054233:0;chr19:9054234-9054348:-1;chr19:9054349-9056171:0;chr19:9056172-9077865:-1;chr19:9077866-9080449:0;chr19:9080450-9080555:-1;chr19:9080556-9082338:0;chr19:9082339-9092018:-1;chr19:9092019-9203919:0;chr19:9203920-9204862:-1;chr19:9204863-9212943:0;chr19:9212944-9213982:-1;chr19:9213983-9225502:0;chr19:9225503-9226439:-1;chr19:9226440-9236686:0;chr19:9236687-9237626:-1;chr19:9237627-9266599:0;chr19:9266600-9266717:-1;chr19:9266718-9267286:0;chr19:9267287-9267424:-1;chr19:9267425-9267942:0;chr19:9267943-9268070:-1;chr19:9268071-9268654:0;chr19:9268655-9268751:-1;chr19:9268752-9269500:0;chr19:9269501-9269584:-1;chr19:9269585-9296268:0;chr19:9296269-9299493:-1;chr19:9299494-9324524:0;chr19:9324525-9325547:-1;chr19:9325548-9361718:0;chr19:9361719-9362739:-1;chr19:9362740-9405984:0;chr19:9405985-9407609:-1;chr19:9407610-9407970:0;chr19:9407971-9408155:-1;chr19:9408156-9408554:0;chr19:9408555-9408666:-1;chr19:9408667-9413052:0;chr19:9413053-9413180:-1;chr19:9413181-9415746:0;chr19:9415747-9415795:-1;chr19:9415796-9579779:0;chr19:9579780-9579863:-1;chr19:9579864-9580304:0;chr19:9580305-9580386:-1;chr19:9580387-9581066:0;chr19:9581067-9581194:-1;chr19:9581195-9581970:0;chr19:9581971-9582054:-1;chr19:9582055-9583853:0;chr19:9583854-9583935:-1;chr19:9583936-9584873:0;chr19:9584874-9585001:-1;chr19:9585002-9585958:0;chr19:9585959-9586045:-1;chr19:9586046-9608802:0;chr19:9608803-9608891:-1;chr19:9608892-9609212:0;chr19:9609213-9609279:-1;chr19:9609280-9638679:0;chr19:9638680-9640312:-1;chr19:9640313-9641659:0;chr19:9641660-9641743:-1;chr19:9641744-9643519:0;chr19:9643520-9643601:-1;chr19:9643602-9644514:0;chr19:9644515-9644642:-1;chr19:9644643-9645862:0;chr19:9645863-9645955:-1;chr19:9645956-9646882:0;chr19:9646883-9647032:-1;chr19:9647033-9648933:0;chr19:9648934-9649021:-1;chr19:9649022-9649249:0;chr19:9649250-9649303:-1;chr19:9649304-9768683:0;chr19:9768684-9768811:-1;chr19:9768812-9770053:0;chr19:9770054-9770143:-1;chr19:9770144-9771394:0;chr19:9771395-9771550:-1;chr19:9771551-9800812:0;chr19:9800813-9801937:-1;chr19:9801938-9804368:0;chr19:9804369-9804496:-1;chr19:9804497-9805453:0;chr19:9805454-9805543:-1;chr19:9805544-9806768:0;chr19:9806769-9806924:-1;chr19:9806925-9810675:0;chr19:9810676-9810762:-1;chr19:9810763-9868149:0;chr19:9868150-9869440:-1;chr19:9869441-9870534:0;chr19:9870535-9870618:-1;chr19:9870619-9872756:0;chr19:9872757-9872844:-1;chr19:9872845-9873956:0;chr19:9873957-9874084:-1;chr19:9874085-9875610:0;chr19:9875611-9875711:-1;chr19:9875712-10102678:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-7743375:0;chr2:100006180-100006312:-1;chr2:100006313-100006680:0;chr2:100006681-100006864:-1;chr2:100006865-100007005:0;chr2:100007006-100007168:-1;chr2:100007169-100009428:0;chr2:100009429-100009561:-1;chr2:100009562-100010728:0;chr2:100010729-100010861:-1;chr2:100010862-100010970:0;chr2:100010971-100011048:-1;chr2:100011049-100011180:0;chr2:100011181-100011346:-1;chr2:100011347-100013221:0;chr2:100013222-100013361:-1;chr2:100013362-100015209:0;chr2:100015210-100015372:-1;chr2:100015373-100018705:0;chr2:100018706-100018809:-1;chr2:100018810-100019105:0;chr2:100019106-100019263:-1;chr2:100019264-100019350:0;chr2:100019351-100019569:-1;chr2:100019570-100020156:0;chr2:100020157-100020278:-1;chr2:100020279-100020905:0;chr2:100020906-100021140:-1;chr2:100021141-100022370:0;chr2:100022371-100022568:-1;chr2:100022569-100022785:0;chr2:100022786-100022952:-1;chr2:100022953-100024489:0;chr2:100024490-100024593:-1;chr2:100024594-100027155:0;chr2:100027156-100027329:-1;chr2:100027330-100029191:0;chr2:100029192-100029413:-1;chr2:100029414-100035288:0;chr2:100035289-100035409:-1;chr2:100035410-100037959:0;chr2:100037960-100038115:-1;chr2:100038116-100040612:0;chr2:100040613-100040742:-1;chr2:100040743-100046300:0;chr2:100046301-100046410:-1;chr2:100046411-100050792:0;chr2:100050793-100050910:-1;chr2:100050911-100052294:0;chr2:100052295-100052403:-1;chr2:100052404-100055061:0;chr2:100055062-100055772:-1;chr2:100055773-100058777:0;chr2:100058778-100058931:-1;chr2:100058932-100065796:0;chr2:100065797-100065966:-1;chr2:100065967-100078956:0;chr2:100078957-100079084:-1;chr2:100079085-100081382:0;chr2:100081383-100081447:-1;chr2:100081448-100360564:0;chr2:100360565-100360602:-1;chr2:100360603-100368681:0;chr2:100368682-100368763:-1;chr2:100368764-100453937:0;chr2:100453938-100453986:-1;chr2:100453987-100623092:0;chr2:100623093-100623479:-1;chr2:100623480-100623608:0;chr2:100623609-100623922:-1;chr2:100623923-100625272:0;chr2:100625273-100625394:-1;chr2:100625395-100627957:0;chr2:100627958-100628033:-1;chr2:100628034-100720862:0;chr2:100720863-100720980:-1;chr2:100720981-100721964:0;chr2:100721965-100722045:-1;chr2:100722046-100758944:0;chr2:100758945-100759037:-1;chr2:100759038-100903374:0;chr2:100903375-100903525:-1;chr2:100903526-100906718:0;chr2:100906719-100906882:-1;chr2:100906883-100910689:0;chr2:100910690-100910849:-1;chr2:100910850-100911892:0;chr2:100911893-100912015:-1;chr2:100912016-100915296:0;chr2:100915297-100915412:-1;chr2:100915413-100915686:0;chr2:100915687-100915781:-1;chr2:100915782-100916177:0;chr2:100916178-100916380:-1;chr2:100916381-100917104:0;chr2:100917105-100917249:-1;chr2:100917250-100919381:0;chr2:100919382-100919505:-1;chr2:100919506-100925567:0;chr2:100925568-100925687:-1;chr2:100925688-100937875:0;chr2:100937876-100939195:-1;chr2:100939196-101011969:0;chr2:101011970-101012076:-1;chr2:101012077-101014368:0;chr2:101014369-101014604:-1;chr2:101014605-101019024:0;chr2:101019025-101019117:-1;chr2:101019118-101023036:0;chr2:101023037-101023169:-1;chr2:101023170-101031501:0;chr2:101031502-101031573:-1;chr2:101031574-101033834:0;chr2:101033835-101034130:-1;chr2:101034131-101086942:0;chr2:101086943-101087026:-1;chr2:101087027-101089255:0;chr2:101089256-101089312:-1;chr2:101089313-101089949:0;chr2:101089950-101090001:-1;chr2:101090002-101093704:0;chr2:101093705-101093729:-1;chr2:101093730-101093821:0;chr2:101093822-101093876:-1;chr2:101093877-101095813:0;chr2:101095814-101095889:-1;chr2:101095890-101096956:0;chr2:101096957-101096993:-1;chr2:101096994-101097586:0;chr2:101097587-101097629:-1;chr2:101097630-101098737:0;chr2:101098738-101098773:-1;chr2:101098774-101099712:0;chr2:101099713-101099742:-1;chr2:101099743-101182963:0;chr2:101182964-101183091:-1;chr2:101183092-101185391:0;chr2:101185392-101185483:-1;chr2:101185484-101186038:0;chr2:101186039-101186183:-1;chr2:101186184-101188050:0;chr2:101188051-101188260:-1;chr2:101188261-101192814:0;chr2:101192815-101193201:-1;chr2:101193202-101436611:0;chr2:101436612-101436876:-1;chr2:101436877-101521193:0;chr2:101521194-101521248:-1;chr2:101521249-101541606:0;chr2:101541607-101541756:-1;chr2:101541757-101549370:0;chr2:101549371-101549463:-1;chr2:101549464-101554213:0;chr2:101554214-101554304:-1;chr2:101554305-101564695:0;chr2:101564696-101564817:-1;chr2:101564818-101565827:0;chr2:101565828-101565942:-1;chr2:101565943-101580518:0;chr2:101580519-101580638:-1;chr2:101580639-101581321:0;chr2:101581322-101581405:-1;chr2:101581406-101582120:0;chr2:101582121-101582228:-1;chr2:101582229-101584741:0;chr2:101584742-101584890:-1;chr2:101584891-101587450:0;chr2:101587451-101587536:-1;chr2:101587537-101591263:0;chr2:101591264-101591406:-1;chr2:101591407-101591918:0;chr2:101591919-101592029:-1;chr2:101592030-101594170:0;chr2:101594171-101594261:-1;chr2:101594262-101598691:0;chr2:101598692-101598839:-1;chr2:101598840-101604539:0;chr2:101604540-101604738:-1;chr2:101604739-101606716:0;chr2:101606717-101606908:-1;chr2:101606909-101607240:0;chr2:101607241-101607334:-1;chr2:101607335-101609807:0;chr2:101609808-101609989:-1;chr2:101609990-101618689:0;chr2:101618690-101618777:-1;chr2:101618778-101619162:0;chr2:101619163-101619270:-1;chr2:101619271-101620618:0;chr2:101620619-101620745:-1;chr2:101620746-101622419:0;chr2:101622420-101622885:-1;chr2:101622811-101622885:-1;chr2:101622886-101623688:0;chr2:101623689-101624735:-1;chr2:101624736-101627389:0;chr2:101627390-101627488:-1;chr2:101627489-101627911:0;chr2:101627912-101628002:-1;chr2:101628003-101638141:0;chr2:101638142-101638208:-1;chr2:101638209-101638741:0;chr2:101638742-101638983:-1;chr2:101638984-101643843:0;chr2:101643844-101643913:-1;chr2:101643914-101644508:0;chr2:101644509-101644608:-1;chr2:101644609-101644763:0;chr2:101644764-101644894:-1;chr2:101644895-101645951:0;chr2:101645952-101646238:-1;chr2:101646239-101648728:0;chr2:101648729-101648847:-1;chr2:101648848-101650004:0;chr2:101650005-101650220:-1;chr2:101650221-101652478:0;chr2:101652479-101652630:-1;chr2:101652631-101653992:0;chr2:101653993-101654170:-1;chr2:101654171-101654921:0;chr2:101654922-101655117:-1;chr2:101655118-101656638:0;chr2:101656639-101656847:-1;chr2:101656848-101666861:0;chr2:101666862-101667103:-1;chr2:101667104-101670568:0;chr2:101670569-101670798:-1;chr2:101670799-101675881:0;chr2:101675882-101676001:-1;chr2:101676002-101706714:0;chr2:101706715-101706826:-1;chr2:101706827-101767587:0;chr2:101767588-101767846:-1;chr2:101767847-101878999:0;chr2:101879000-101879153:-1;chr2:101879154-101881305:0;chr2:101881306-101881509:-1;chr2:101881510-101883137:0;chr2:101883138-101883341:-1;chr2:101883342-101885500:0;chr2:101885501-101885598:-1;chr2:101885599-101898319:0;chr2:101898320-101898519:-1;chr2:101898520-101902541:0;chr2:101902542-101902639:-1;chr2:101902640-101905433:0;chr2:101905434-101905517:-1;chr2:101905518-101910474:0;chr2:101910475-101910544:-1;chr2:101910545-101911391:0;chr2:101911392-101911643:-1;chr2:101911644-102018896:0;chr2:102018897-102019214:-1;chr2:102019215-102022403:0;chr2:102022404-102022519:-1;chr2:102022520-102027079:0;chr2:102027080-102027175:-1;chr2:102027176-102029375:0;chr2:102029376-102029533:-1;chr2:102029534-102031314:0;chr2:102031315-102031374:-1;chr2:102031375-102033994:0;chr2:102033995-102034146:-1;chr2:102034147-102035311:0;chr2:102035312-102035426:-1;chr2:102035427-102038184:0;chr2:102038185-102038239:-1;chr2:102038240-102038822:0;chr2:102038823-102038934:-1;chr2:102038935-102083237:0;chr2:102083238-102083362:-1;chr2:102083363-102091096:0;chr2:102091097-102091165:-1;chr2:102091166-102314536:0;chr2:102314537-102314599:-1;chr2:102314600-102314933:0;chr2:102314934-102315000:-1;chr2:102315001-102407180:0;chr2:102407181-102407238:-1;chr2:102407239-102440388:0;chr2:102440389-102440515:-1;chr2:102440516-102441779:0;chr2:102441780-102441891:-1;chr2:102441892-102445964:0;chr2:102445965-102446056:-1;chr2:102446057-102448181:0;chr2:102448182-102448313:-1;chr2:102448314-102450869:0;chr2:102450870-102450925:-1;chr2:102450926-102452360:0;chr2:102452361-102452440:-1;chr2:102452441-102456279:0;chr2:102456280-102456456:-1;chr2:102456457-102459069:0;chr2:102459070-102459143:-1;chr2:102459144-102460561:0;chr2:102460562-102460773:-1;chr2:102460774-152739763:0;chr2:14236933-14237049:-1;chr2:14237050-79862173:0;chr2:152739764-152739884:1;chr2:152739885-152830181:0;chr2:152830182-152830485:1;chr2:152830486-152954842:0;chr2:152954843-152954927:1;chr2:152954928-152955153:0;chr2:152955154-152955235:1;chr2:152955236-152980278:0;chr2:152980279-152980449:1;chr2:152980450-152982738:0;chr2:152982739-152982893:1;chr2:152982894-152988626:0;chr2:152988627-152988682:1;chr2:152988683-152989685:0;chr2:152989686-152989774:1;chr2:152989775-152989914:0;chr2:152989915-152989998:1;chr2:152989999-152992021:0;chr2:152992022-152992117:1;chr2:152992118-153000339:0;chr2:153000340-153000527:1;chr2:153000528-153001400:0;chr2:153001401-153001471:1;chr2:153001472-153003674:0;chr2:153003675-153003822:1;chr2:153003823-153004536:0;chr2:153004537-153004636:1;chr2:153004637-153004737:0;chr2:153004738-153004814:1;chr2:153004815-153006657:0;chr2:153006658-153006743:1;chr2:153006744-153378455:0;chr2:153378456-153378540:1;chr2:153378541-153399251:0;chr2:153399252-153399333:1;chr2:153399334-153486168:0;chr2:153486169-153486238:1;chr2:153486239-153486337:0;chr2:153486338-153486419:1;chr2:153486420-153488520:0;chr2:153488521-153488651:1;chr2:153488652-153492939:0;chr2:153492940-153493104:1;chr2:153493105-153494085:0;chr2:153494086-153494188:1;chr2:153494189-153496470:0;chr2:153496471-153496570:1;chr2:153496571-153497303:0;chr2:153497304-153497428:1;chr2:153497429-153514401:0;chr2:153514402-153514534:1;chr2:153514535-153515460:0;chr2:153515461-153515523:1;chr2:153515524-153515605:0;chr2:153515606-153515703:1;chr2:153515704-153515782:0;chr2:153515783-153515870:1;chr2:153515871-153519115:0;chr2:153519116-153519212:1;chr2:153519213-153519547:0;chr2:153519548-153519686:1;chr2:153519687-153520167:0;chr2:153520168-153520285:1;chr2:153520286-153520388:0;chr2:153520389-153520481:1;chr2:153520482-153520650:0;chr2:153520651-153520766:1;chr2:153520767-153525649:0;chr2:153525650-153525784:1;chr2:153525785-153526743:0;chr2:153526744-153526895:1;chr2:153526896-153527785:0;chr2:153527786-153527895:1;chr2:153527896-153528971:0;chr2:153528972-153529137:1;chr2:153529138-153529490:0;chr2:153529491-153529556:1;chr2:153529557-153530110:0;chr2:153530111-153530220:1;chr2:153530221-153532917:0;chr2:153532918-153533293:1;chr2:153533294-153533963:0;chr2:153533964-153533989:1;chr2:153533990-153535568:0;chr2:153535569-153535623:1;chr2:153535624-153535864:0;chr2:153535865-153535986:1;chr2:153535987-153537738:0;chr2:153537739-153537850:1;chr2:153537851-153547474:0;chr2:153547475-153547492:1;chr2:153547493-153549550:0;chr2:153549551-153549582:1;chr2:153549583-153551054:0;chr2:153551055-153551136:1;chr2:153551137-160801415:0;chr2:160801416-160801593:-1;chr2:160801594-160803310:0;chr2:160803311-160803428:-1;chr2:160803317-160803428:-1;chr2:160803429-160803928:0;chr2:160803929-160804070:-1;chr2:160804071-160806117:0;chr2:160806118-160806287:-1;chr2:160806288-160807849:0;chr2:160807850-160808089:-1;chr2:160808090-160811708:0;chr2:160811709-160811857:-1;chr2:160811858-160812207:0;chr2:160812208-160812339:-1;chr2:160812340-160813019:0;chr2:160813020-160813138:-1;chr2:160813139-160824048:0;chr2:160824049-160824189:-1;chr2:160824190-160825765:0;chr2:160825766-160825870:-1;chr2:160825871-160826657:0;chr2:160826658-160826723:-1;chr2:160826724-160832577:0;chr2:160832578-160832736:-1;chr2:160832737-160833194:0;chr2:160833195-160833231:-1;chr2:160833232-160833793:0;chr2:160833794-160833927:-1;chr2:160833928-160836339:0;chr2:160836340-160836425:-1;chr2:160836426-160840437:0;chr2:160840438-160840584:-1;chr2:160840585-160843665:0;chr2:160843666-160843869:-1;chr2:160843870-160862161:0;chr2:160862162-160862332:-1;chr2:160862333-160869772:0;chr2:160869773-160869886:-1;chr2:160869887-160873123:0;chr2:160873124-160873223:-1;chr2:160873224-160876615:0;chr2:160876616-160876774:-1;chr2:160876775-160879174:0;chr2:160879175-160879370:-1;chr2:160879371-160884727:0;chr2:160884728-160884872:-1;chr2:160884873-160885359:0;chr2:160885360-160885474:-1;chr2:160885475-160889468:0;chr2:160889469-160889643:-1;chr2:160889644-160898534:0;chr2:160898535-160898709:-1;chr2:160898710-160901283:0;chr2:160901284-160901668:-1;chr2:160901669-160964188:0;chr2:160964189-160964356:-1;chr2:160964357-160968589:0;chr2:160968590-160968710:-1;chr2:160968711-160980300:0;chr2:160980301-160980399:-1;chr2:160980400-160982888:0;chr2:160982889-160983112:-1;chr2:160983113-160993943:0;chr2:160993944-160994362:-1;chr2:160994363-160994574:0;chr2:160994575-160994710:-1;chr2:160994711-160998491:0;chr2:160998492-160998582:-1;chr2:160998583-161025721:0;chr2:161025722-161025818:-1;chr2:161025819-161029078:0;chr2:161029079-161029241:-1;chr2:161029242-161030483:0;chr2:161030484-161030650:-1;chr2:161030651-161051878:0;chr2:161051879-161052126:-1;chr2:161052127-161052725:0;chr2:161052726-161052931:-1;chr2:161052932-161055688:0;chr2:161055689-161055769:-1;chr2:161055770-161056512:0;chr2:161056513-161056590:-1;chr2:161056591-161132139:0;chr2:161132140-161132225:-1;chr2:161132226-161133812:0;chr2:161133813-161133894:-1;chr2:161133895-161135057:0;chr2:161135058-161135169:-1;chr2:161135170-161137823:0;chr2:161137824-161137875:-1;chr2:161137876-161141284:0;chr2:161141285-161141379:-1;chr2:161141380-161141504:0;chr2:161141505-161141555:-1;chr2:161141556-161143478:0;chr2:161143479-161143595:-1;chr2:161143488-161143595:-1;chr2:161143596-161157160:0;chr2:161157161-161157241:-1;chr2:161157242-161159839:0;chr2:161159840-161159998:-1;chr2:161159999-161169665:0;chr2:161169666-161169758:-1;chr2:161169759-161174678:0;chr2:161174679-161174738:-1;chr2:161174739-161223725:0;chr2:161223726-161223902:-1;chr2:161223903-162016937:0;chr2:162016938-162016997:-1;chr2:162016998-162036123:0;chr2:162036124-162036272:-1;chr2:162036273-162164784:0;chr2:162164785-162165115:-1;chr2:162165116-162172946:0;chr2:162172947-162173080:-1;chr2:162173081-162175331:0;chr2:162175332-162175384:-1;chr2:162175385-162223987:0;chr2:162223988-162224060:-1;chr2:162224061-162224293:0;chr2:162224294-162224414:-1;chr2:162224415-162226616:0;chr2:162226617-162226688:-1;chr2:162226689-162227681:0;chr2:162227682-162227833:-1;chr2:162227834-162241973:0;chr2:162241974-162242082:-1;chr2:162242083-162247613:0;chr2:162247614-162247689:-1;chr2:162247690-162251587:0;chr2:162251588-162251714:-1;chr2:162251715-162265346:0;chr2:162265347-162265410:-1;chr2:162265411-162267811:0;chr2:162267812-162268228:-1;chr2:162268229-162272618:0;chr2:162272619-162273613:-1;chr2:162273614-162274185:0;chr2:162274186-162274341:-1;chr2:162274342-162274710:0;chr2:162274711-162274833:-1;chr2:162274834-162275401:0;chr2:162275402-162275561:-1;chr2:162275562-162276705:0;chr2:162276706-162276768:-1;chr2:162276769-162480843:0;chr2:162480844-162481076:-1;chr2:162481077-162565202:0;chr2:162565203-162565339:-1;chr2:162565340-162627481:0;chr2:162627482-162627564:-1;chr2:162627565-162660957:0;chr2:162660958-162661105:-1;chr2:162661106-162696297:0;chr2:162696298-162696437:-1;chr2:162696438-162711478:0;chr2:162711479-162711640:-1;chr2:162711641-162719382:0;chr2:162719383-162719572:-1;chr2:162719573-162728801:0;chr2:162728802-162728894:-1;chr2:162728895-162730424:0;chr2:162730425-162730515:-1;chr2:162730516-162735639:0;chr2:162735640-162735798:-1;chr2:162735799-162738865:0;chr2:162738866-162738954:-1;chr2:162738955-162751187:0;chr2:162751188-162751335:-1;chr2:162751336-162757419:0;chr2:162757420-162757521:-1;chr2:162757522-162760512:0;chr2:162760513-162760688:-1;chr2:162760689-162761284:0;chr2:162761285-162761419:-1;chr2:162761420-162762150:0;chr2:162762151-162762397:-1;chr2:162762398-162799300:0;chr2:162799301-162799407:-1;chr2:162799408-162804074:0;chr2:162804075-162804237:-1;chr2:162804238-162805656:0;chr2:162805657-162805771:-1;chr2:162805772-162807195:0;chr2:162807196-162807358:-1;chr2:162807359-162813497:0;chr2:162813498-162813750:-1;chr2:162813751-162814995:0;chr2:162814996-162815065:-1;chr2:162815066-162820643:0;chr2:162820644-162820818:-1;chr2:162820819-162821559:0;chr2:162821560-162821683:-1;chr2:162821684-162830757:0;chr2:162830758-162830826:-1;chr2:162830827-162833268:0;chr2:162833269-162833386:-1;chr2:162833387-162834230:0;chr2:162834231-162834270:-1;chr2:162834271-162851469:0;chr2:162851470-162851544:-1;chr2:162851545-162862253:0;chr2:162862254-162862319:-1;chr2:162862320-162865070:0;chr2:162865071-162865171:-1;chr2:162865172-162865749:0;chr2:162865750-162865805:-1;chr2:162865806-162868301:0;chr2:162868302-162868497:-1;chr2:162868498-162870904:0;chr2:162870905-162870975:-1;chr2:162870976-162873276:0;chr2:162873277-162873376:-1;chr2:162873377-162873616:0;chr2:162873617-162873665:-1;chr2:162873666-162875237:0;chr2:162875238-162875360:-1;chr2:162875361-162875731:0;chr2:162875732-162875786:-1;chr2:162875787-162876737:0;chr2:162876738-162876806:-1;chr2:162876807-162877089:0;chr2:162877090-162877198:-1;chr2:162877199-162879263:0;chr2:162879264-162879309:-1;chr2:162879310-162881312:0;chr2:162881313-162881449:-1;chr2:162881450-162890049:0;chr2:162890050-162890163:-1;chr2:162890164-162891672:0;chr2:162891673-162891834:-1;chr2:162891835-162894810:0;chr2:162894811-162894932:-1;chr2:162894933-162895457:0;chr2:162895458-162895531:-1;chr2:162895532-162895640:0;chr2:162895641-162895694:-1;chr2:162895695-162902040:0;chr2:162902041-162902122:-1;chr2:162902123-162903423:0;chr2:162903424-162903516:-1;chr2:162903517-162903911:0;chr2:162903912-162904011:-1;chr2:162904012-162929907:0;chr2:162929908-162929996:-1;chr2:162929997-162999377:0;chr2:162999378-162999880:-1;chr2:162999881-163000535:0;chr2:163000536-163000680:-1;chr2:163000681-163002048:0;chr2:163002049-163002187:-1;chr2:163002188-163003861:0;chr2:163003862-163004024:-1;chr2:163004025-163005595:0;chr2:163005596-163005697:-1;chr2:163005698-163008666:0;chr2:163008667-163008914:-1;chr2:163008915-163027198:0;chr2:163027199-163027590:-1;chr2:163027591-163029319:0;chr2:163029320-163029394:-1;chr2:163029395-163029657:0;chr2:163029658-163029731:-1;chr2:163029732-163030231:0;chr2:163030232-163030297:-1;chr2:163030298-163031375:0;chr2:163031376-163031476:-1;chr2:163031477-163039922:0;chr2:163039923-163039978:-1;chr2:163039979-163044677:0;chr2:163044678-163044873:-1;chr2:163044874-163045611:0;chr2:163045612-163045682:-1;chr2:163045683-163046164:0;chr2:163046165-163046264:-1;chr2:163046265-163051209:0;chr2:163051210-163051258:-1;chr2:163051259-163055265:0;chr2:163055266-163055391:-1;chr2:163055392-163057074:0;chr2:163057075-163057129:-1;chr2:163057130-163059380:0;chr2:163059381-163059452:-1;chr2:163059453-163059549:0;chr2:163059550-163059655:-1;chr2:163059656-163066460:0;chr2:163066461-163066506:-1;chr2:163066507-163070446:0;chr2:163070447-163070583:-1;chr2:163070584-163072406:0;chr2:163072407-163072511:-1;chr2:163072512-163074494:0;chr2:163074495-163074650:-1;chr2:163074651-163075571:0;chr2:163075572-163075693:-1;chr2:163075694-163076361:0;chr2:163076362-163076435:-1;chr2:163076436-163080116:0;chr2:163080117-163080170:-1;chr2:163080171-163080974:0;chr2:163080975-163081050:-1;chr2:163081051-163081991:0;chr2:163081992-163082087:-1;chr2:163082088-163083031:0;chr2:163083032-163083131:-1;chr2:163083132-163099416:0;chr2:163099417-163099502:-1;chr2:163099503-163099830:0;chr2:163099831-163100045:-1;chr2:163100046-163123587:0;chr2:163123588-163123889:-1;chr2:163123890-163123987:0;chr2:163123988-163124079:-1;chr2:163124080-163124595:0;chr2:163124596-163124787:-1;chr2:163124788-163128734:0;chr2:163128735-163128897:-1;chr2:163128898-163130303:0;chr2:163130304-163130454:-1;chr2:163130455-163133195:0;chr2:163133196-163133456:-1;chr2:163133457-163133923:0;chr2:163133924-163134203:-1;chr2:163134204-163134713:0;chr2:163134714-163134838:-1;chr2:163134839-163136504:0;chr2:163136505-163136622:-1;chr2:163136623-163137836:0;chr2:163137837-163138055:-1;chr2:163138056-163138874:0;chr2:163138875-163139086:-1;chr2:163139087-163144643:0;chr2:163144644-163144865:-1;chr2:163144866-163150072:0;chr2:163150073-163150178:-1;chr2:163150179-163163217:0;chr2:163163218-163163365:-1;chr2:163163366-163167273:0;chr2:163167274-163167443:-1;chr2:163167444-163174363:0;chr2:163174364-163175218:-1;chr2:163175219-163204086:0;chr2:163204087-163204252:-1;chr2:163204253-163208846:0;chr2:163208847-163208917:-1;chr2:163208918-163212946:0;chr2:163212947-163212991:-1;chr2:163212992-163213266:0;chr2:163213267-163213415:-1;chr2:163213416-163215552:0;chr2:163215553-163215667:-1;chr2:163215668-163216002:0;chr2:163216003-163216062:-1;chr2:163216063-163229978:0;chr2:163229979-163230172:-1;chr2:163230173-163236361:0;chr2:163236362-163236531:-1;chr2:163236532-163241196:0;chr2:163241197-163241449:-1;chr2:163241450-163250897:0;chr2:163250898-163250995:-1;chr2:163250996-163253248:0;chr2:163253249-163253455:-1;chr2:163253456-163256697:0;chr2:163256698-163256951:-1;chr2:163256952-163279755:0;chr2:163279756-163280045:-1;chr2:163279845-163280045:-1;chr2:163280046-163291706:0;chr2:163291707-163292107:-1;chr2:163292108-163302526:0;chr2:163302527-163302953:-1;chr2:163302954-163360951:0;chr2:163360952-163361167:-1;chr2:163361168-163369162:0;chr2:163369163-163369184:-1;chr2:163369185-163374238:0;chr2:163374239-163374668:-1;chr2:163374669-163393433:0;chr2:163393434-163393590:-1;chr2:163393591-163693045:0;chr2:163693046-163693277:-1;chr2:163693278-164591411:0;chr2:164591412-164591582:-1;chr2:164591583-189342384:0;chr2:189342385-189342457:1;chr2:189342458-189348156:0;chr2:189348157-189348219:1;chr2:189348220-189387481:0;chr2:189387482-189387554:1;chr2:189387555-189393822:0;chr2:189393823-189393922:1;chr2:189393923-189405906:0;chr2:189405907-189406045:1;chr2:189406046-189433964:0;chr2:189433965-189434082:1;chr2:189434083-189434753:0;chr2:189434754-189434847:1;chr2:189434848-189448990:0;chr2:189448991-189449130:1;chr2:189449131-189452580:0;chr2:189452581-189452676:1;chr2:189452677-189454465:0;chr2:189454466-189454477:1;chr2:189454478-189598463:0;chr2:189598464-189599676:1;chr2:189599677-189654588:0;chr2:189654589-189654831:1;chr2:189654832-189849484:0;chr2:189849485-189849688:1;chr2:189849485-189859058:1;chr2:189849689-189849921:0;chr2:189849922-189849973:1;chr2:189849974-189850389:0;chr2:189850390-189850504:1;chr2:189850505-189851783:0;chr2:189851784-189851865:1;chr2:189851866-189852805:0;chr2:189852806-189852860:1;chr2:189852861-189853314:0;chr2:189853315-189853369:1;chr2:189853370-189854120:0;chr2:189854121-189854175:1;chr2:189854176-189854820:0;chr2:189854821-189854875:1;chr2:189854876-189855031:0;chr2:189855032-189855086:1;chr2:189855087-189855728:0;chr2:189855729-189855783:1;chr2:189855784-189856211:0;chr2:189856212-189856257:1;chr2:189856258-189856393:0;chr2:189856394-189856448:1;chr2:189856449-189856908:0;chr2:189856909-189856954:1;chr2:189856955-189857611:0;chr2:189857612-189857666:1;chr2:189857667-189858085:0;chr2:189858086-189858185:1;chr2:189858186-189858762:0;chr2:189858763-189858808:1;chr2:189858809-189858958:0;chr2:189858959-189859058:1;chr2:189859059-189968988:0;chr2:189968989-189969003:1;chr2:189968989-190044605:1;chr2:189969004-189974949:0;chr2:189974950-189975175:1;chr2:189975176-190044232:0;chr2:190044233-190044605:1;chr2:190044606-190306157:0;chr2:190306158-190306304:1;chr2:190306305-190313103:0;chr2:190313104-190313234:1;chr2:190313235-190315627:0;chr2:190315628-190315694:1;chr2:190315695-190316529:0;chr2:190316530-190316621:1;chr2:190316622-190320044:0;chr2:190320045-190320170:1;chr2:190320171-190322035:0;chr2:190322036-190322107:1;chr2:190322108-190323477:0;chr2:190323478-190323598:1;chr2:190323599-190324060:0;chr2:190324061-190324150:1;chr2:190324151-190327208:0;chr2:190327209-190327368:1;chr2:190327369-190328418:0;chr2:190328419-190328479:1;chr2:190328480-190328570:0;chr2:190328571-190328687:1;chr2:190328688-190329803:0;chr2:190329804-190329980:1;chr2:190329981-190331149:0;chr2:190331150-190331308:1;chr2:190331309-190332192:0;chr2:190332193-190332374:1;chr2:190332375-190333199:0;chr2:190333200-190333295:1;chr2:190333296-190334068:0;chr2:190334069-190334165:1;chr2:190334166-190334800:0;chr2:190334801-190334971:1;chr2:190334972-190335543:0;chr2:190335544-190335604:1;chr2:190335605-190338910:0;chr2:190338911-190339058:1;chr2:190339059-190339441:0;chr2:190339442-190339534:1;chr2:190339535-190339937:0;chr2:190339938-190340264:1;chr2:190340265-190428308:0;chr2:190428309-190428951:1;chr2:190428952-225661031:0;chr2:225661032-225661143:-1;chr2:225661144-225661679:0;chr2:225661680-225661863:-1;chr2:225661864-225662547:0;chr2:225662548-225662686:-1;chr2:225662687-225664866:0;chr2:225664867-225664980:-1;chr2:225664981-225666631:0;chr2:225666632-225666757:-1;chr2:225666758-225668827:0;chr2:225668828-225668930:-1;chr2:225668931-225669509:0;chr2:225669510-225669558:-1;chr2:225669559-225669773:0;chr2:225669774-225669841:-1;chr2:225669842-225669921:0;chr2:225669922-225670037:-1;chr2:225670038-225670123:0;chr2:225670124-225670246:-1;chr2:225670247-225670841:0;chr2:225670842-225670954:-1;chr2:225670955-225672383:0;chr2:225672384-225672501:-1;chr2:225672502-225672626:0;chr2:225672627-225672803:-1;chr2:225672804-225679035:0;chr2:225679036-225679081:-1;chr2:225679082-225681332:0;chr2:225681333-225681430:-1;chr2:225681431-225684161:0;chr2:225684162-225684246:-1;chr2:225684247-225688216:0;chr2:225688217-225688364:-1;chr2:225688365-225695256:0;chr2:225695257-225695329:-1;chr2:225695330-225698865:0;chr2:225698866-225698980:-1;chr2:225698981-225702477:0;chr2:225702478-225702548:-1;chr2:225702549-225704669:0;chr2:225704670-225704789:-1;chr2:225704790-225706519:0;chr2:225706520-225706613:-1;chr2:225706614-243199373:0;chr2:7743376-7743490:-1;chr2:7743491-7743808:0;chr2:7743809-7743869:-1;chr2:7743870-14236932:0;chr2:79862174-79862311:-1;chr2:79862312-79865011:0;chr2:79865012-79865145:-1;chr2:79865146-95539263:0;chr2:95539264-95539335:-1;chr2:95539336-95539708:0;chr2:95539709-95539853:-1;chr2:95539854-95541331:0;chr2:95541332-95541487:-1;chr2:95541488-95542296:0;chr2:95542297-95542568:-1;chr2:95542569-95691398:0;chr2:95691399-95691630:-1;chr2:95691631-95713702:0;chr2:95713703-95713871:-1;chr2:95713872-95715324:0;chr2:95715325-95715451:-1;chr2:95715452-95756129:0;chr2:95756130-95756267:-1;chr2:95756268-95766217:0;chr2:95766218-95766281:-1;chr2:95766282-95766580:0;chr2:95766581-95766639:-1;chr2:95766640-95767420:0;chr2:95767421-95767468:-1;chr2:95767469-95770383:0;chr2:95770384-95770475:-1;chr2:95770476-95772166:0;chr2:95772167-95772202:-1;chr2:95772203-95773918:0;chr2:95773919-95774153:-1;chr2:95774154-95775659:0;chr2:95775660-95775786:-1;chr2:95775787-95780809:0;chr2:95780810-95780948:-1;chr2:95780949-95783608:0;chr2:95783609-95783690:-1;chr2:95783691-95787477:0;chr2:95787478-95787754:-1;chr2:95787755-95818417:0;chr2:95818418-95818514:-1;chr2:95818515-95818876:0;chr2:95818877-95819004:-1;chr2:95819005-95823094:0;chr2:95823095-95823184:-1;chr2:95823185-95824983:0;chr2:95824984-95825263:-1;chr2:95825264-95831181:0;chr2:95831182-95831605:-1;chr2:95831606-95841931:0;chr2:95841932-95842004:-1;chr2:95842005-95843226:0;chr2:95843227-95843354:-1;chr2:95843355-95845902:0;chr2:95845903-95846017:-1;chr2:95846018-95940199:0;chr2:95940200-95940577:-1;chr2:95940578-95941207:0;chr2:95941208-95941258:-1;chr2:95941259-95963070:0;chr2:95963071-95963201:-1;chr2:95963202-95976101:0;chr2:95976102-95976268:-1;chr2:95976269-96012766:0;chr2:96012767-96012870:-1;chr2:96012871-96040042:0;chr2:96040043-96040168:-1;chr2:96040169-96040594:0;chr2:96040595-96040665:-1;chr2:96040666-96040884:0;chr2:96040885-96040956:-1;chr2:96040957-96047342:0;chr2:96047343-96047451:-1;chr2:96047452-96048978:0;chr2:96048979-96049042:-1;chr2:96049043-96071299:0;chr2:96071300-96071551:-1;chr2:96071552-96072687:0;chr2:96072688-96072905:-1;chr2:96072906-96076273:0;chr2:96076274-96076334:-1;chr2:96076335-96076610:0;chr2:96076611-96076774:-1;chr2:96076775-96078180:0;chr2:96078181-96078290:-1;chr2:96078291-96078423:0;chr2:96078424-96078512:-1;chr2:96078513-96078641:0;chr2:96078642-96078879:-1;chr2:96078880-96795801:0;chr2:96795802-96795884:-1;chr2:96795885-96798277:0;chr2:96798278-96798460:-1;chr2:96798461-96799162:0;chr2:96799163-96799281:-1;chr2:96799282-96799702:0;chr2:96799703-96799797:-1;chr2:96799798-96801088:0;chr2:96801089-96801151:-1;chr2:96801152-96803312:0;chr2:96803313-96803439:-1;chr2:96803440-96804119:0;chr2:96804120-96804175:-1;chr2:96804176-96809891:0;chr2:96809892-96810112:-1;chr2:96810113-96810498:0;chr2:96810499-96810621:-1;chr2:96810622-96810704:0;chr2:96810705-96811179:-1;chr2:96811180-96858105:0;chr2:96858106-96858206:-1;chr2:96858207-96858814:0;chr2:96858815-96858898:-1;chr2:96858899-96858978:0;chr2:96858979-96859090:-1;chr2:96859091-96860694:0;chr2:96860695-96860745:-1;chr2:96860746-96861077:0;chr2:96861078-96861287:-1;chr2:96861288-96920569:0;chr2:96920570-96920735:-1;chr2:96920736-96931605:0;chr2:96931606-96931751:-1;chr2:96931752-96931882:0;chr2:96931883-96932227:-1;chr2:96932228-96933057:0;chr2:96933058-96933207:-1;chr2:96933208-96933361:0;chr2:96933362-96933474:-1;chr2:96933475-96933572:0;chr2:96933573-96933662:-1;chr2:96933663-96934193:0;chr2:96934194-96934396:-1;chr2:96934397-96935004:0;chr2:96935005-96935093:-1;chr2:96935094-96942640:0;chr2:96942641-96942723:-1;chr2:96942724-96942817:0;chr2:96942818-96942979:-1;chr2:96942980-96943275:0;chr2:96943276-96943453:-1;chr2:96943454-96943543:0;chr2:96943544-96943688:-1;chr2:96943689-96943973:0;chr2:96943974-96944096:-1;chr2:96944097-96944283:0;chr2:96944284-96944449:-1;chr2:96944450-96944545:0;chr2:96944546-96944736:-1;chr2:96944737-96945187:0;chr2:96945188-96945297:-1;chr2:96945298-96947550:0;chr2:96947551-96947660:-1;chr2:96947661-96948937:0;chr2:96948938-96949090:-1;chr2:96949091-96949271:0;chr2:96949272-96949451:-1;chr2:96949452-96949549:0;chr2:96949550-96949742:-1;chr2:96949743-96950094:0;chr2:96950095-96950323:-1;chr2:96950324-96950916:0;chr2:96950917-96951078:-1;chr2:96951079-96952047:0;chr2:96952048-96952222:-1;chr2:96952223-96952424:0;chr2:96952425-96952615:-1;chr2:96952616-96952742:0;chr2:96952743-96952898:-1;chr2:96952899-96953175:0;chr2:96953176-96953295:-1;chr2:96953296-96953599:0;chr2:96953600-96953707:-1;chr2:96953708-96954399:0;chr2:96954400-96954484:-1;chr2:96954485-96954773:0;chr2:96954774-96954855:-1;chr2:96954856-96954963:0;chr2:96954964-96955117:-1;chr2:96955118-96955535:0;chr2:96955536-96955734:-1;chr2:96955735-96956062:0;chr2:96956063-96956252:-1;chr2:96956253-96956420:0;chr2:96956421-96956553:-1;chr2:96956554-96957128:0;chr2:96957129-96957240:-1;chr2:96957241-96957487:0;chr2:96957488-96957638:-1;chr2:96957639-96958708:0;chr2:96958709-96958833:-1;chr2:96958834-96959052:0;chr2:96959053-96959247:-1;chr2:96959248-96961224:0;chr2:96961225-96961396:-1;chr2:96961397-96962272:0;chr2:96962273-96962429:-1;chr2:96962430-96962669:0;chr2:96962670-96962808:-1;chr2:96962809-96963099:0;chr2:96963100-96963274:-1;chr2:96963275-96963373:0;chr2:96963374-96963458:-1;chr2:96963459-96964020:0;chr2:96964021-96964158:-1;chr2:96964159-96964339:0;chr2:96964340-96964440:-1;chr2:96964441-96964551:0;chr2:96964552-96964705:-1;chr2:96964706-96965065:0;chr2:96965066-96965165:-1;chr2:96965166-96966734:0;chr2:96966735-96966791:-1;chr2:96966792-96967260:0;chr2:96967261-96967454:-1;chr2:96967455-96968895:0;chr2:96968896-96969068:-1;chr2:96969069-96991060:0;chr2:96991061-96991303:-1;chr2:96991068-96991303:-1;chr2:96991304-96991483:0;chr2:96991484-96991587:-1;chr2:96991588-96991933:0;chr2:96991934-96994091:-1;chr2:96991944-96992046:-1;chr2:96992379-96994091:-1;chr2:96994092-97007378:0;chr2:97007379-97007632:-1;chr2:97007633-97007786:0;chr2:97007787-97007878:-1;chr2:97007879-97008492:0;chr2:97008493-97008586:-1;chr2:97008587-97008902:0;chr2:97008903-97009042:-1;chr2:97009043-97009841:0;chr2:97009842-97009967:-1;chr2:97009968-97017567:0;chr2:97017568-97017758:-1;chr2:97017759-97019042:0;chr2:97019043-97019135:-1;chr2:97019136-97019919:0;chr2:97019920-97020126:-1;chr2:97020127-97024781:0;chr2:97024782-97024931:-1;chr2:97024932-97025879:0;chr2:97025880-97025987:-1;chr2:97025988-97026324:0;chr2:97026325-97026448:-1;chr2:97026449-97030217:0;chr2:97030218-97030329:-1;chr2:97030330-97031612:0;chr2:97031613-97031796:-1;chr2:97031797-97032993:0;chr2:97032994-97033111:-1;chr2:97033112-97034708:0;chr2:97034709-97034801:-1;chr2:97034802-97035161:0;chr2:97035162-97035238:-1;chr2:97035239-97216309:0;chr2:97216310-97216470:-1;chr2:97216471-97216834:0;chr2:97216835-97218371:-1;chr2:97218372-97267378:0;chr2:97267379-97267513:-1;chr2:97267514-97267851:0;chr2:97267852-97268075:-1;chr2:97268076-97268488:0;chr2:97268489-97268599:-1;chr2:97268600-97269985:0;chr2:97269986-97270117:-1;chr2:97270118-97270514:0;chr2:97270515-97270600:-1;chr2:97270601-97271055:0;chr2:97271056-97271248:-1;chr2:97271249-97274243:0;chr2:97274244-97274401:-1;chr2:97274402-97274599:0;chr2:97274600-97274801:-1;chr2:97274802-97275234:0;chr2:97275235-97275299:-1;chr2:97275300-97276461:0;chr2:97276462-97276620:-1;chr2:97276621-97276799:0;chr2:97276800-97276875:-1;chr2:97276876-97278017:0;chr2:97278018-97278090:-1;chr2:97278091-97278197:0;chr2:97278198-97278300:-1;chr2:97278301-97278553:0;chr2:97278554-97278671:-1;chr2:97278672-97279223:0;chr2:97279224-97279356:-1;chr2:97279357-97285094:0;chr2:97285095-97285281:-1;chr2:97285282-97285407:0;chr2:97285408-97285499:-1;chr2:97285500-97297047:0;chr2:97297048-97297219:-1;chr2:97297220-97302656:0;chr2:97302657-97302922:-1;chr2:97302923-97304018:0;chr2:97304019-97304116:-1;chr2:97304117-97308572:0;chr2:97308573-97308658:-1;chr2:97308659-97312136:0;chr2:97312137-97312190:-1;chr2:97312191-97312799:0;chr2:97312800-97312892:-1;chr2:97312893-97313513:0;chr2:97313514-97313623:-1;chr2:97313624-97315358:0;chr2:97315359-97315414:-1;chr2:97315415-97315915:0;chr2:97315916-97316026:-1;chr2:97316027-97317627:0;chr2:97317628-97317757:-1;chr2:97317758-97319375:0;chr2:97319376-97319439:-1;chr2:97319440-97326076:0;chr2:97326077-97326108:-1;chr2:97326109-97327060:0;chr2:97327061-97327177:-1;chr2:97327178-97327403:0;chr2:97327404-97327528:-1;chr2:97327529-97327950:0;chr2:97327951-97328004:-1;chr2:97328005-97329174:0;chr2:97329175-97329244:-1;chr2:97329245-97334486:0;chr2:97334487-97334531:-1;chr2:97334532-97334621:0;chr2:97334622-97334741:-1;chr2:97334742-97334778:0;chr2:97334779-97334874:-1;chr2:97334875-97335854:0;chr2:97335855-97335984:-1;chr2:97335985-97338812:0;chr2:97338813-97338991:-1;chr2:97338992-97350062:0;chr2:97350063-97350188:-1;chr2:97350189-97351064:0;chr2:97351065-97351166:-1;chr2:97351167-97351930:0;chr2:97351931-97352087:-1;chr2:97352088-97353551:0;chr2:97353552-97353684:-1;chr2:97353685-97354948:0;chr2:97354949-97355113:-1;chr2:97355114-97355379:0;chr2:97355380-97355495:-1;chr2:97355496-97356222:0;chr2:97356223-97356320:-1;chr2:97356321-97356925:0;chr2:97356926-97357090:-1;chr2:97357091-97357180:0;chr2:97357181-97357349:-1;chr2:97357350-97357458:0;chr2:97357459-97357700:-1;chr2:97357701-97357839:0;chr2:97357840-97357918:-1;chr2:97357919-97359241:0;chr2:97359242-97359424:-1;chr2:97359425-97359646:0;chr2:97359647-97359809:-1;chr2:97359810-97360095:0;chr2:97360096-97360201:-1;chr2:97360202-97361244:0;chr2:97361245-97361398:-1;chr2:97361399-97361477:0;chr2:97361478-97361641:-1;chr2:97361642-97361787:0;chr2:97361788-97361814:-1;chr2:97361815-97363261:0;chr2:97363262-97363313:-1;chr2:97363314-97363395:0;chr2:97363396-97363498:-1;chr2:97363499-97363772:0;chr2:97363773-97363893:-1;chr2:97363894-97364406:0;chr2:97364407-97364569:-1;chr2:97364570-97364780:0;chr2:97364781-97364873:-1;chr2:97364874-97365285:0;chr2:97365286-97365457:-1;chr2:97365458-97365667:0;chr2:97365668-97365817:-1;chr2:97365818-97366067:0;chr2:97366068-97366208:-1;chr2:97366209-97367690:0;chr2:97367691-97367780:-1;chr2:97367781-97368014:0;chr2:97368015-97368138:-1;chr2:97368139-97368335:0;chr2:97368336-97368478:-1;chr2:97368479-97368713:0;chr2:97368714-97368814:-1;chr2:97368815-97368888:0;chr2:97368889-97369083:-1;chr2:97369084-97369258:0;chr2:97369259-97369369:-1;chr2:97369370-97369950:0;chr2:97369951-97370099:-1;chr2:97370100-97370203:0;chr2:97370204-97370624:-1;chr2:97370625-97373449:0;chr2:97373450-97373570:-1;chr2:97373571-97377391:0;chr2:97377392-97377507:-1;chr2:97377508-97377599:0;chr2:97377600-97377762:-1;chr2:97377763-97378842:0;chr2:97378843-97378876:-1;chr2:97378877-97399254:0;chr2:97399255-97399338:-1;chr2:97399339-97400144:0;chr2:97400145-97400263:-1;chr2:97400264-97403684:0;chr2:97403685-97403804:-1;chr2:97403805-97405589:0;chr2:97405590-97405813:-1;chr2:97405814-97462747:0;chr2:97462748-97462892:-1;chr2:97462893-97463248:0;chr2:97463249-97463384:-1;chr2:97463385-97464792:0;chr2:97464793-97464963:-1;chr2:97464964-97465287:0;chr2:97465288-97465385:-1;chr2:97465386-97474296:0;chr2:97474297-97474479:-1;chr2:97474480-97492568:0;chr2:97492569-97492719:-1;chr2:97492720-97493466:0;chr2:97493467-97493637:-1;chr2:97493638-97493834:0;chr2:97493835-97493932:-1;chr2:97493933-97494302:0;chr2:97494303-97494437:-1;chr2:97494438-97507795:0;chr2:97507796-97507922:-1;chr2:97507923-97508100:0;chr2:97508101-97508248:-1;chr2:97508249-97509701:0;chr2:97509702-97509758:-1;chr2:97509759-97519136:0;chr2:97519137-97519341:-1;chr2:97519342-97520073:0;chr2:97520074-97520178:-1;chr2:97520179-97523623:0;chr2:97523624-97523756:-1;chr2:97523757-97529417:0;chr2:97529418-97529531:-1;chr2:97529532-97529661:0;chr2:97529662-97529885:-1;chr2:97529886-97529973:0;chr2:97529974-97530119:-1;chr2:97530120-97530440:0;chr2:97530441-97530617:-1;chr2:97530618-97530699:0;chr2:97530700-97530852:-1;chr2:97530853-97530939:0;chr2:97530940-97531057:-1;chr2:97531058-97531176:0;chr2:97531177-97531274:-1;chr2:97531275-97531401:0;chr2:97531402-97531501:-1;chr2:97531502-97531602:0;chr2:97531603-97531666:-1;chr2:97531667-97532018:0;chr2:97532019-97532168:-1;chr2:97532169-97533513:0;chr2:97533514-97533660:-1;chr2:97533661-97535611:0;chr2:97535612-97535735:-1;chr2:97535736-97543625:0;chr2:97543626-97543779:-1;chr2:97543780-97544151:0;ch2:97544152-97544230:-1;chr2:97544231-97559661:0;chr2:97559662-97559788:-1;chr2:97559789-97560796:0;chr2:97560797-97560899:-1;chr2:97560900-97563649:0;chr2:97563650-97563870:-1;chr2:97563871-97568355:0;chr2:97568356-97568444:-1;chr2:97568445-97586900:0;chr2:97586901-97586999:-1;chr2:97587000-97587213:0;chr2:97587214-97587391:-1;chr2:97587392-97589225:0;chr2:97589226-97589320:-1;chr2:97589321-97594941:0;chr2:97594942-97595057:-1;chr2:97595058-97613553:0;chr2:97613554-97613639:-1;chr2:97613640-97617114:0;chr2:97617115-97617221:-1;chr2:97617222-97626023:0;chr2:97626024-97626177:-1;chr2:97626178-97633255:0;chr2:97633256-97633364:-1;chr2:97633365-97636451:0;chr2:97636452-97636514:-1;chr2:97636515-97637636:0;chr2:97637637-97638059:-1;chr2:97638060-97638273:0;chr2:97638274-97638343:-1;chr2:97638344-97651976:0;chr2:97651977-97652301:-1;chr2:97652302-97749683:0;chr2:97749684-97749772:-1;chr2:97749773-97749904:0;chr2:97749905-97750014:-1;chr2:97750015-97751434:0;chr2:97751435-97751598:-1;chr2:97751599-97751874:0;chr2:97751875-97751935:-1;chr2:97751936-97755844:0;chr2:97755845-97756062:-1;chr2:97756063-97757197:0;chr2:97757198-97757449:-1;chr2:97757450-97760436:0;chr2:97760437-97760582:-1;chr2:97760583-97779231:0;chr2:97779232-97779673:-1;chr2:97779674-97783799:0;chr2:97783800-97783915:-1;chr2:97783916-97784079:0;chr2:97784080-97784254:-1;chr2:97784255-97788622:0;chr2:97788623-97788730:-1;chr2:97788731-97790195:0;chr2:97790196-97790334:-1;chr2:97790335-97792802:0;chr2:97792803-97792871:-1;chr2:97792872-97808375:0;chr2:97808376-97808405:-1;chr2:97808406-97808498:0;chr2:97808499-97808572:-1;chr2:97808573-97810253:0;chr2:97810254-97810283:-1;chr2:97810284-97810375:0;chr2:97810376-97810449:-1;chr2:97810450-97845596:0;chr2:97845597-97845670:-1;chr2:97845671-97847333:0;chr2:97847334-97847363:-1;chr2:97847364-97847456:0;chr2:97847457-97847530:-1;chr2:97847531-97849194:0;chr2:97849195-97849224:-1;chr2:97849225-97849317:0;chr2:97849318-97849391:-1;chr2:97849392-97851051:0;chr2:97851052-97851081:-1;chr2:97851082-97851173:0;chr2:97851174-97851247:-1;chr2:97851248-97852933:0;chr2:97852934-97852963:-1;chr2:97852964-97853064:0;chr2:97853065-97853138:-1;chr2:97853139-97854822:0;chr2:97854823-97854852:-1;chr2:97854853-97854953:0;chr2:97854954-97855027:-1;chr2:97855028-97856713:0;chr2:97856714-97856743:-1;chr2:97856744-97856844:0;chr2:97856845-97856918:-1;chr2:97856919-97858593:0;chr2:97858594-97858623:-1;chr2:97858624-97858716:0;chr2:97858717-97858790:-1;chr2:97858791-97860461:0;chr2:97860462-97860491:-1;chr2:97860492-97860580:0;chr2:97860581-97860654:-1;chr2:97860655-97862328:0;chr2:97862329-97862358:-1;chr2:97862359-97862451:0;chr2:97862452-97862525:-1;chr2:97862526-97864198:0;chr2:97864199-97864228:-1;chr2:97864229-97864321:0;chr2:97864322-97864395:-1;chr2:97864396-97866069:0;chr2:97866070-97866099:-1;chr2:97866100-97866188:0;chr2:97866189-97866262:-1;chr2:97866263-97867937:0;chr2:97867938-97867967:-1;chr2:97867968-97868056:0;chr2:97868057-97868130:-1;chr2:97868131-97869803:0;chr2:97869804-97869833:-1;chr2:97869834-97869926:0;chr2:97869927-97870000:-1;chr2:97870001-97871675:0;chr2:97871676-97871705:-1;chr2:97871706-97871798:0;chr2:97871799-97871872:-1;chr2:97871873-97873546:0;chr2:97873547-97873576:-1;chr2:97873577-97873669:0;chr2:97873670-97873743:-1;chr2:97873744-97875416:0;chr2:97875417-97875446:-1;chr2:97875447-97875535:0;chr2:97875536-97875609:-1;chr2:97875610-97877281:0;chr2:97877282-97877311:-1;chr2:97877312-97877404:0;chr2:97877405-97877478:-1;chr2:97877479-97879154:0;chr2:97879155-97879184:-1;chr2:97879185-97881036:0;chr2:97881037-97881066:-1;chr2:97881067-97881160:0;chr2:97881161-97881312:-1;chr2:97881313-97882912:0;chr2:97882913-97882942:-1;chr2:97882943-97883035:0;chr2:97883036-97883109:-1;chr2:97883110-97884909:0;chr2:97884910-97884983:-1;chr2:97884984-97890541:0;chr2:97890542-97890616:-1;chr2:97890617-97899465:0;chr2:97899466-97899608:-1;chr2:97899609-97907001:0;chr2:97907002-97907216:-1;chr2:97907217-97909581:0;chr2:97909582-97909766:-1;chr2:97909767-98376113:0;chr2:98376114-98376212:-1;chr2:98376213-98377054:0;chr2:98377055-98377152:-1;chr2:98377153-98377254:0;chr2:98377255-98377377:-1;chr2:98377378-98378496:0;chr2:98378497-98378663:-1;chr2:98378664-98382575:0;chr2:98382576-98382726:-1;chr2:98382727-98382939:0;chr2:98382940-98383065:-1;chr2:98383066-98388758:0;chr2:98388759-98388887:-1;chr2:98388888-98392304:0;chr2:98392305-98392481:-1;chr2:98392482-98408847:0;chr2:98408848-98409447:-1;chr2:98409448-98409856:0;chr2:98409857-98410016:-1;chr2:98410017-98411391:0;chr2:98411392-98411578:-1;chr2:98411579-98412679:0;chr2:98412680-98412867:-1;chr2:98412868-98413305:0;chr2:98413306-98413449:-1;chr2:98413450-98413826:0;chr2:98413827-98413979:-1;chr2:98413980-98418356:0;chr2:98418357-98418424:-1;chr2:98418425-98418889:0;chr2:98418890-98419000:-1;chr2:98419001-98419113:0;chr2:98419114-98419253:-1;chr2:98419254-98421549:0;chr2:98421550-98421668:-1;chr2:98421669-98421837:0;chr2:98421838-98421914:-1;chr2:98421915-98422012:0;chr2:98422013-98422166:-1;chr2:98422167-98426149:0;chr2:98426150-98426237:-1;chr2:98426238-98427589:0;chr2:98427590-98427695:-1;chr2:98427696-98428882:0;chr2:98428883-98429018:-1;chr2:98429019-98429100:0;chr2:98429101-98429212:-1;chr2:98429213-98430432:0;chr2:98430433-98430604:-1;chr2:98430605-98430696:0;chr2:98430697-98430851:-1;chr2:98430852-98431660:0;chr2:98431661-98431770:-1;chr2:98431771-98435074:0;chr2:98435075-98435184:-1;chr2:98435185-98449826:0;chr2:98449827-98449889:-1;chr2:98449890-98451082:0;chr2:98451083-98451140:-1;chr2:98451141-98451236:0;chr2:98451237-98451388:-1;chr2:98451389-98453538:0;chr2:98453539-98453620:-1;chr2:98453621-98458276:0;chr2:98458277-98458400:-1;chr2:98458401-98460606:0;chr2:98460607-98460724:-1;chr2:98460725-98475765:0;chr2:98475766-98475890:-1;chr2:98475891-98504513:0;chr2:98504514-98504583:-1;chr2:98504584-98525119:0;chr2:98525120-98525161:-1;chr2:98525162-98543887:0;chr2:98543888-98543950:-1;chr2:98543951-98611937:0;chr2:98611938-98612354:-1;chr2:98612355-98732113:0;chr2:98732114-98732209:-1;chr2:98732210-98735974:0;chr2:98735975-98736226:-1;chr2:98736227-98737760:0;chr2:98737761-98737921:-1;chr2:98737922-98744700:0;chr2:98744701-98744871:-1;chr2:98744872-98750285:0;chr2:98750286-98750402:-1;chr2:98750403-98779312:0;chr2:98779313-98779439:-1;chr2:98779440-98797477:0;chr2:98797478-98797675:-1;chr2:98797676-98804436:0;chr2:98804437-98804592:-1;chr2:98804593-98809359:0;chr2:98809360-98809499:-1;chr2:98809500-98810822:0;chr2:98810823-98810955:-1;chr2:98810956-98828391:0;chr2:98828392-98828491:-1;chr2:98828492-98834307:0;chr2:98834308-98834491:-1;chr2:98834492-98844663:0;chr2:98844664-98844795:-1;chr2:98844796-98846511:0;chr2:98846512-98846670:-1;chr2:98846671-98851109:0;chr2:98851110-98851230:-1;chr2:98851231-98852851:0;chr2:98852852-98852940:-1;chr2:98852941-98853035:0;chr2:98853036-98853193:-1;chr2:98853194-98866779:0;chr2:98866780-98866899:-1;chr2:98866900-98872585:0;chr2:98872586-98872637:-1;chr2:98872638-98887143:0;chr2:98887144-98887346:-1;chr2:98887347-98906972:0;chr2:98906973-98907085:-1;chr2:98907086-98914368:0;chr2:98914369-98914494:-1;chr2:98914495-98916540:0;chr2:98916541-98916679:-1;chr2:98916680-98920163:0;chr2:98920164-98920265:-1;chr2:98920266-98928280:0;chr2:98928281-98928495:-1;chr2:98928496-98962616:0;chr2:98962617-98962997:-1;chr2:98962998-98986400:0;chr2:98986401-98986539:-1;chr2:98986540-98994148:0;chr2:98994149-98994263:-1;chr2:98994264-98996636:0;chr2:98996637-98996817:-1;chr2:98996818-98999849:0;chr2:98999850-98999904:-1;chr2:98999905-99006119:0;chr2:99006120-99006237:-1;chr2:99006238-99008325:0;chr2:99008326-99008433:-1;chr2:99008434-99135425:0;chr2:99135426-99135488:-1;chr2:99135489-99136407:0;chr2:99136408-99136617:-1;chr2:99136618-99137148:0;chr2:99137149-99137194:-1;chr2:99137195-99149838:0;chr2:99149839-99149958:-1;chr2:99149959-99152190:0;chr2:99152191-99152308:-1;chr2:99152309-99152590:0;chr2:99152591-99152671:-1;chr2:99152672-99154324:0;chr2:99154325-99154437:-1;chr2:99154438-99155352:0;chr2:99155353-99155444:-1;chr2:99155445-99155989:0;chr2:99155990-99156138:-1;chr2:99156139-99160338:0;chr2:99160339-99160470:-1;chr2:99160471-99162430:0;chr2:99162431-99162536:-1;chr2:99162537-99163047:0;chr2:99163048-99163157:-1;chr2:99163158-99165416:0;chr2:99165417-99165432:-1;chr2:99165433-99169247:0;chr2:99169248-99169432:-1;chr2:99169433-99170732:0;chr2:99170733-99170952:-1;chr2:99170953-99172014:0;chr2:99172015-99172271:-1;chr2:99172272-99175924:0;chr2:99175925-99175958:-1;chr2:99175959-99179926:0;chr2:99179927-99180100:-1;chr2:99180101-99181101:0;chr2:99181102-99181226:-1;chr2:99181227-99182101:0;chr2:99182102-99182229:-1;chr2:99182230-99182490:0;chr2:99182491-99182632:-1;chr2:99182633-99185032:0;chr2:99185033-99185131:-1;chr2:99185132-99189276:0;chr2:99189277-99189390:-1;chr2:99189391-99193450:0;chr2:99193451-99193606:-1;chr2:99193607-99198037:0;chr2:99198038-99198284:-1;chr2:99198285-99220569:0;chr2:99220570-99220654:-1;chr2:99220655-99224768:0;chr2:99224769-99224981:-1;chr2:99224982-99225040:0;chr2:99225041-99225189:-1;chr2:99225190-99226217:0;chr2:99226218-99226502:-1;chr2:99226503-99227236:0;chr2:99227237-99227358:-1;chr2:99227359-99232668:0;chr2:99232669-99232809:-1;chr2:99232810-99232893:0;chr2:99232894-99232996:-1;chr2:99232997-99234629:0;chr2:99234630-99234977:-1;chr2:99234978-99242184:0;chr2:99242185-99242298:-1;chr2:99242299-99251683:0;chr2:99251684-99251751:-1;chr2:99251752-99252978:0;chr2:99252979-99253058:-1;chr2:99253059-99256269:0;chr2:99256270-99256464:-1;chr2:99256465-99256582:0;chr2:99256583-99256691:-1;chr2:99256692-99260384:0;chr2:99260385-99260516:-1;chr2:99260517-99261889:0;chr2:99261890-99262005:-1;chr2:99262006-99271906:0;chr2:99271907-99271983:-1;chr2:99271984-99272813:0;chr2:99272814-99272928:-1;chr2:99272929-99274679:0;chr2:99274680-99274727:-1;chr2:99274728-99279507:0;chr2:99279508-99279642:-1;chr2:99279643-99279802:0;chr2:99279803-99279936:-1;chr2:99279937-99291496:0;chr2:99291497-99291638:-1;chr2:99291639-99294765:0;chr2:99294766-99294934:-1;chr2:99294935-99342700:0;chr2:99342701-99343030:-1;chr2:99343031-99347509:0;chr2:99347510-99347589:-1;chr2:99347590-99412581:0;chr2:99412582-99412727:-1;chr2:99412728-99413811:0;chr2:99413812-99414000:-1;chr2:99414001-99443436:0;chr2:99443437-99443632:-1;chr2:99443633-99448809:0;chr2:99448810-99448975:-1;chr2:99448976-99449323:0;chr2:99449324-99449460:-1;chr2:99449461-99454580:0;chr2:99454581-99454750:-1;chr2:99454751-99634661:0;chr2:99634662-99634812:-1;chr2:99634813-99634997:0;chr2:99634998-99635103:-1;chr2:99635104-99636741:0;chr2:99636742-99636945:-1;chr2:99636946-99651691:0;chr2:99651692-99651902:-1;chr2:99651903-99681400:0;chr2:99681401-99681587:-1;chr2:99681588-99685349:0;chr2:99685350-99685461:-1;chr2:99685462-99688167:0;chr2:99688168-99688337:-1;chr2:99688338-99689479:0;chr2:99689480-99689536:-1;chr2:99689537-99695120:0;chr2:99695121-99695276:-1;chr2:99695277-99697743:0;chr2:99697744-99697860:-1;chr2:99697861-99720428:0;chr2:99720429-99720581:-1;chr2:99720582-99721820:0;chr2:99721821-99721899:-1;chr2:99721900-99721988:0;chr2:99721989-99722160:-1;chr2:99722161-99725294:0;chr2:99725295-99725454:-1;chr2:99725455-99725850:0;chr2:99725851-99725975:-1;chr2:99725976-99766944:0;chr2:99766945-99767928:-1;chr2:99767929-99771416:0;chr2:99771417-99771514:-1;chr2:99771515-99771535:0;chr2:99771536-99771831:-1;chr2:99771832-99772762:0;chr2:99772763-99772889:-1;chr2:99772890-99773188:0;chr2:99773189-99773317:-1;chr2:99773318-99774758:0;chr2:99774759-99774875:-1;chr2:99774876-99778418:0;chr2:99778419-99779613:-1;chr2:99779614-99785724:0;chr2:99785725-99785933:-1;chr2:99785934-99786011:0;chr2:99786012-99786073:-1;chr2:99786074-99786998:0;chr2:99786999-99787115:-1;chr2:99787116-99787804:0;chr2:99787805-99787892:-1;chr2:99787893-99787971:0;chr2:99787972-99788109:-1;chr2:99788110-99790376:0;chr2:99790377-99790479:-1;chr2:99790480-99797292:0;chr2:99797293-99797492:-1;chr2:99797493-99802638:0;chr2:99802639-99802717:-1;chr2:99802718-99804638:0;chr2:99804639-99804720:-1;chr2:99804721-99811212:0;chr2:99811213-99811360:-1;chr2:99811361-99811577:0;chr2:99811578-99811652:-1;chr2:99811653-99858709:0;chr2:99858710-99858945:-1;chr2:99858946-99860460:0;chr2:99860461-99860600:-1;chr2:99860601-99861723:0;chr2:99861724-99861921:-1;chr2:99861922-99863141:0;chr2:99863142-99863283:-1;chr2:99863284-99870679:0;chr2:99870680-99870748:-1;chr2:99870749-99871481:0;chr2:99871482-99871570:-1;chr2:99871571-99900699:0;chr2:99900700-99900974:-1;chr2:99900975-99901149:0;chr2:99901150-99901283:-1;chr2:99901284-99907698:0;chr2:99907699-99907884:-1;chr2:99907885-99908997:0;chr2:99908998-99909103:-1;chr2:99909104-99912089:0;chr2:99912090-99912165:-1;chr2:99912166-99914920:0;chr2:99914921-99915012:-1;chr2:99915013-99917511:0;chr2:99917512-99917639:-1;chr2:99917640-99938416:0;chr2:99938417-99938672:-1;chr2:99938673-99943996:0;chr2:99943997-99944116:-1;chr2:99944117-99949483:0;chr2:99949484-99949705:-1;chr2:99949706-99952700:0;chr2:99952701-99952860:-1;chr2:99952861-99976697:0;chr2:99976698-99976824:-1;chr2:99976825-99976926:0;chr2:99976927-99977012:-1;chr2:99977013-99977609:0;chr2:99977610-99978283:-1;chr2:99978284-99980106:0;chr2:99980107-99980325:-1;chr2:99980326-99980732:0;chr2:99980733-99980884:-1;chr2:99980885-99984954:0;chr2:99984955-99985054:-1;chr2:99985055-99985853:0;chr2:99985854-99985944:-1;chr2:99985945-99988117:0;chr2:99988118-99988193:-1;chr2:99988194-99992808:0;chr2:99992809-99993099:-1;chr2:99993100-99995480:0;chr2:99995481-99995589:-1;chr2:99995590-99995779:0;chr2:99995780-99995891:-1;chr2:99995892-99998620:0;chr2:99998621-99998689:-1;chr2:99998690-99999241:0;chr2:99999242-99999384:-1;chr2:99999385-100006179:0;chr3:0-198022430:0;chr4:0-13371493:0;chr4:13371494-13371589:1;chr4:13371494-13485989:1;chr4:13371590-13373417:0;chr4:13373418-13373491:1;chr4:13373492-13378167:0;chr4:13378168-13378246:1;chr4:13378247-13383113:0;chr4:13383114-13383218:1;chr4:13383219-13462321:0;chr4:13462322-13462452:1;chr4:13462453-13475940:0;chr4:13475941-13476030:1;chr4:13476031-13481052:0;chr4:13481053-13481150:1;chr4:13481151-13485698:0;chr4:13485699-13485989:1;chr4:13485990-13545571:0;chr4:13545572-13546114:1;chr4:13546115-13578460:0;chr4:13578461-13578615:1;chr4:13578461-13589395:1;chr4:13578616-13579025:0;chr4:13579026-13579111:1;chr4:13579112-13579204:0;chr4:13579205-13579255:1;chr4:13579256-13581550:0;chr4:13581551-13581597:1;chr4:13581598-13582642:0;chr4:13582643-13582678:1;chr4:13582679-13582754:0;chr4:13582755-13582831:1;chr4:13582832-13583859:0;chr4:13583860-13583934:1;chr4:13583935-13584274:0;chr4:13584275-13584360:1;chr4:13584361-13588018:0;chr4:13588019-13588099:1;chr4:13588100-13589321:0;chr4:13589322-13589395:1;chr4:13589396-15564976:0;chr4:15564977-15565145:1;chr4:15565146-15568998:0;chr4:15568999-15569105:1;chr4:15569106-15569298:0;chr4:15569299-15569409:1;chr4:15569410-15570914:0;chr4:15570915-15571012:1;chr4:15571013-15572019:0;chr4:15572020-15572119:1;chr4:15572120-15575771:0;chr4:15575772-15575949:1;chr4:15575950-15581589:0;chr4:15581590-15581794:1;chr4:15581795-15587778:0;chr4:15587779-15587869:1;chr4:15587870-15589437:0;chr4:15589438-15589552:1;chr4:15589553-15591166:0;chr4:15591167-15591302:1;chr4:15591303-15597706:0;chr4:15597707-15597830:1;chr4:15597831-15599028:0;chr4:15599029-15599088:1;chr4:15599089-15601150:0;chr4:15601151-15601329:1;chr4:15601330-15602858:0;chr4:15602859-15603180:1;chr4:15603181-15613887:0;chr4:15613888-15614037:1;chr4:15613888-15657035:1;chr4:15614038-15626873:0;chr4:15626874-15627600:1;chr4:15627601-15628494:0;chr4:15628495-15628578:1;chr4:15628579-15629506:0;chr4:15629507-15629656:1;chr4:15629657-15632287:0;chr4:15632288-15632414:1;chr4:15632415-15638115:0;chr4:15638116-15638299:1;chr4:15638300-15640129:0;chr4:15640130-15640317:1;chr4:15640318-15642409:0;chr4:15642410-15642506:1;chr4:15642507-15646114:0;chr4:15646115-15646280:1;chr4:15646281-15656825:0;chr4:15656826-15657035:1;chr4:15657036-15683350:0;chr4:15683351-15683524:1;chr4:15683351-15692070:1;chr4:15683525-15687857:0;chr4:15687858-15692070:1;chr4:15692071-16168254:0;chr4:16168255-16168416:1;chr4:16168255-16228161:1;chr4:16168417-16172274:0;chr4:16172275-16172352:1;chr4:16172353-16175825:0;chr4:16175826-16175895:1;chr4:16175896-16176291:0;chr4:16176292-16176352:1;chr4:16176353-16177740:0;chr4:16177741-16177851:1;chr4:16177852-16181198:0;chr4:16181199-16181280:1;chr4:16181281-16188156:0;chr4:16188157-16188227:1;chr4:16188228-16188402:0;chr4:16188403-16188501:1;chr4:16188502-16189841:0;chr4:16189842-16189978:1;chr4:16189979-16192982:0;chr4:16192983-16193146:1;chr4:16193147-16204083:0;chr4:16204084-16204203:1;chr4:16204204-16215389:0;chr4:16215390-16215521:1;chr4:16215522-16227880:0;chr4:16227881-16228161:1;chr4:16228162-16507461:0;chr4:16507462-16507605:1;chr4:16507462-16900424:1;chr4:16507606-16510156:0;chr4:16510157-16510309:1;chr4:16510310-16513602:0;chr4:16513603-16513727:1;chr4:16513728-16587543:0;chr4:16587544-16587628:1;chr4:16587629-16590331:0;chr4:16590332-16590455:1;chr4:16590456-16597324:0;chr4:16597325-16597498:1;chr4:16597499-16760779:0;chr4:16760780-16760883:1;chr4:16760884-16899975:0;chr4:16899976-16900424:1;chr4:16900425-17492283:0;chr4:17492284-17492368:1;chr4:17492369-17503340:0;chr4:17503341-17503482:1;chr4:17503483-17506000:0;chr4:17506001-17506098:1;chr4:17506099-17838780:0;chr4:17838781-17838963:1;chr4:17838964-17839248:0;chr4:17839249-17839424:1;chr4:17839425-17841297:0;chr4:17841298-17841460:1;chr4:17841461-17841692:0;chr4:17841693-17841832:1;chr4:17841833-17842228:0;chr4:17842229-17842316:1;chr4:17842317-17843931:0;chr4:17843932-17844002:1;chr4:17844003-17887689:0;chr4:17887690-17887784:1;chr4:17887690-18023483:1;chr4:17887785-17910715:0;chr4:17910716-17910968:1;chr4:17910969-17963524:0;chr4:17963525-17963655:1;chr4:17963656-17964591:0;chr4:17964592-17964672:1;chr4:17964673-17974441:0;chr4:17974442-17974508:1;chr4:17974509-18023219:0;chr4:18023220-18023483:1;chr4:18023484-20255233:0;chr4:20255234-20255617:1;chr4:20255234-20512189:1;chr4:20255618-20258293:0;chr4:20258294-20258366:1;chr4:20258367-20259489:0;chr4:20259490-20259562:1;chr4:20259563-20270431:0;chr4:20270432-20270504:1;chr4:20270505-20469373:0;chr4:20469374-20469446:1;chr4:20469447-20482337:0;chr4:20482338-20482410:1;chr4:20482411-20487821:0;chr4:20487822-20487894:1;chr4:20487895-20490440:0;chr4:20490441-20490605:1;chr4:20490606-20493382:0;chr4:20493383-20493522:1;chr4:20493523-20512116:0;chr4:20512117-20512189:1;chr4:20512190-25315666:0;chr4:25315667-25315786:1;chr4:25315667-25366788:1;chr4:25315787-25316938:0;chr4:25316939-25317022:1;chr4:25317023-25334803:0;chr4:25334804-25335080:1;chr4:25335081-25335528:0;chr4:25335529-25335610:1;chr4:25335611-25347168:0;chr4:25347169-25347242:1;chr4:25347243-25351112:0;chr4:25351113-25351264:1;chr4:25351265-25353209:0;chr4:25353210-25353311:1;chr4:25353312-25363479:0;chr4:25363480-25363602:1;chr4:25363603-25363846:0;chr4:25363847-25363923:1;chr4:25363924-25366074:0;chr4:25366075-25366127:1;chr4:25366128-25366642:0;chr4:25366643-25366788:1;chr4:25366789-25378846:0;chr4:25378847-25378966:1;chr4:25378967-25381994:0;chr4:25381995-25382101:1;chr4:25382102-25384881:0;chr4:25384882-25385015:1;chr4:25385016-25390120:0;chr4:25390121-25390196:1;chr4:25390197-25390337:0;chr4:25390338-25390365:1;chr4:25390366-25390458:0;chr4:25390459-25390504:1;chr4:25390505-25391756:0;chr4:25391757-25391842:1;chr4:25391843-25392531:0;chr4:25392532-25392637:1;chr4:25392638-25393958:0;chr4:25393959-25394043:1;chr4:25394044-25395425:0;chr4:25395426-25395513:1;chr4:25395514-25395930:0;chr4:25395931-25395996:1;chr4:25395997-25396291:0;chr4:25396292-25396335:1;chr4:25396336-25396449:0;chr4:25396450-25396527:1;chr4:25396528-25398284:0;chr4:25398285-25398386:1;chr4:25398387-25398468:0;chr4:25398469-25398521:1;chr4:25398522-25404591:0;chr4:25404592-25404648:1;chr4:25404649-25407193:0;chr4:25407194-25407241:1;chr4:25407242-25408449:0;chr4:25408450-25408507:1;chr4:25408508-25408817:0;chr4:25408818-25408875:1;chr4:25408876-25411318:0;chr4:25411319-25411413:1;chr4:25411414-25415265:0;chr4:25415266-25415364:1;chr4:25415365-25415944:0;chr4:25415945-25416007:1;chr4:25416008-25416086:0;chr4:25416087-25416126:1;chr4:25416127-25416219:0;chr4:25416220-25416322:1;chr4:25416323-25417086:0;chr4:25417087-25417162:1;chr4:25417163-25418045:0;chr4:25418046-25418220:1;chr4:25418221-25419236:0;chr4:25419237-25419361:1;chr4:25419362-42571176:0;chr4:42571177-42571222:1;chr4:42571177-42629126:1;chr4:42571223-42576634:0;chr4:42576635-42576724:1;chr4:42576725-42577637:0;chr4:42577638-42577716:1;chr4:42577717-42580275:0;chr4:42580276-42580404:1;chr4:42580405-42581828:0;chr4:42581829-42581995:1;chr4:42581996-42583636:0;chr4:42583637-42583749:1;chr4:42583750-42588364:0;chr4:42588365-42588493:1;chr4:42588494-42590275:0;chr4:42590276-42590346:1;chr4:42590347-42592826:0;chr4:42592827-42592901:1;chr4:42592902-42596304:0;chr4:42596305-42596379:1;chr4:42596380-42602493:0;chr4:42602494-42602535:1;chr4:42602536-42618048:0;chr4:42618049-42618095:1;chr4:42618096-42626551:0;chr4:42626552-42626651:1;chr4:42626652-42627629:0;chr4:42627630-42627730:1;chr4:42627731-42629010:0;chr4:42629011-42629126:1;chr4:42629127-42895281:0;chr4:42895282-42895667:1;chr4:42895668-42964907:0;chr4:42964908-42965151:1;chr4:42965152-43022369:0;chr4:43022370-43022436:1;chr4:43022437-43032376:0;chr4:43032377-43032675:1;chr4:43032676-44624352:0;chr4:44624353-44624593:1;chr4:44624594-44626616:0;chr4:44626617-44626799:1;chr4:44626800-44631418:0;chr4:44631419-44631565:1;chr4:44631566-44637937:0;chr4:44637938-44638102:1;chr4:44638103-44652000:0;chr4:44652001-44652118:1;chr4:44652119-44653569:0;chr4:44653570-44653658:1;chr4:44653659-44682456:0;chr4:44682457-44682569:1;chr4:44682570-44682709:0;chr4:44682710-44682859:1;chr4:44682860-44683138:0;chr4:44683139-44683220:1;chr4:44683221-44684349:0;chr4:44684350-44684428:1;chr4:44684429-44685250:0;chr4:44685251-44685335:1;chr4:44685336-44687974:0;chr4:44687975-44688040:1;chr4:44688041-44688525:0;chr4:44688526-44688730:1;chr4:44688731-44690022:0;chr4:44690023-44690163:1;chr4:44690164-44691301:0;chr4:44691302-44691426:1;chr4:44691427-44691858:0;chr4:44691859-44691992:1;chr4:44691993-44692732:0;chr4:44692733-44692877:1;chr4:44692878-44693681:0;chr4:44693682-44693816:1;chr4:44693817-44696427:0;chr4:44696428-44696530:1;chr4:44696531-44697630:0;chr4:44697631-44697751:1;chr4:44697752-48542368:0;chr4:48542369-48542977:1;chr4:48542369-48577258:1;chr4:48542978-48544042:0;chr4:48544043-48544138:1;chr4:48544139-48545822:0;chr4:48545823-48546014:1;chr4:48546015-48546798:0;chr4:48546799-48546921:1;chr4:48546922-48548082:0;chr4:48548083-48548288:1;chr4:48548289-48549599:0;chr4:48549600-48549786:1;chr4:48549787-48550705:0;chr4:48550706-48550810:1;chr4:48550811-48551488:0;chr4:48551489-48551640:1;chr4:48551641-48552607:0;chr4:48552608-48552721:1;chr4:48552722-48553509:0;chr4:48553510-48553595:1;chr4:48553596-48555230:0;chr4:48555231-48555400:1;chr4:48555401-48558993:0;chr4:48558994-48559135:1;chr4:48559136-48559468:0;chr4:48559469-48559729:1;chr4:48559730-48563483:0;chr4:48563484-48563653:1;chr4:48563654-48564904:0;chr4:48564905-48565005:1;chr4:48565006-48565963:0;chr4:48565964-48566119:1;chr4:48566120-48566948:0;chr4:48566949-48567060:1;chr4:48567061-48567546:0;chr4:48567547-48567708:1;chr4:48567709-48569263:0;chr4:48569264-48569437:1;chr4:48569438-48572842:0;chr4:48572843-48572935:1;chr4:48572936-48575201:0;chr4:48575202-48575260:1;chr4:48575261-48577132:0;chr4:48577133-48577258:1;chr4:48577259-54245390:0;chr4:54245391-54245431:1;chr4:54245432-54248443:0;chr4:54248444-54248502:1;chr4:54248503-54249938:0;chr4:54249939-54250043:1;chr4:54250044-54255974:0;chr4:54255975-54256040:1;chr4:54256041-54256686:0;chr4:54256687-54256795:1;chr4:54256796-54257174:0;chr4:54257175-54257306:1;chr4:54257307-54257595:0;chr4:54257596-54257665:1;chr4:54257666-54265895:0;chr4:54265896-54266006:1;chr4:54266007-54280780:0;chr4:54280781-54280889:1;chr4:54280890-54292037:0;chr4:54292038-54292132:1;chr4:54292133-54294192:0;chr4:54294193-54294350:1;chr4:54294351-54306747:0;chr4:54306748-54306775:1;chr4:54306776-54308818:0;chr4:54308819-54308874:1;chr4:54308875-54310213:0;chr4:54310214-54310270:1;chr4:54310271-54319085:0;chr4:54319086-54319300:1;chr4:54319301-54324818:0;chr4:54324819-54324957:1;chr4:54324958-54325467:0;chr4:54325468-54326103:1;chr4:54326104-54327600:0;chr4:54327601-54327760:1;chr4:54327601-54344909:1;chr4:54327761-54342918:0;chr4:54342919-54343148:1;chr4:54343149-54344730:0;chr4:54344731-54344909:1;chr4:54344910-55138559:0;chr4:55138560-55138687:1;chr4:55138560-55156721:1;chr4:55138688-55139702:0;chr4:55139703-55139897:1;chr4:55139898-55140696:0;chr4:55140697-55140792:1;chr4:55140793-55141006:0;chr4:55141007-55141140:1;chr4:55141141-55143553:0;chr4:55143554-55143659:1;chr4:55143660-55144061:0;chr4:55144062-55144173:1;chr4:55144174-55144527:0;chr4:55144528-55144682:1;chr4:55144683-55146481:0;chr4:55146482-55146649:1;chr4:55146650-55151536:0;chr4:55151537-55151653:1;chr4:55151654-55152006:0;chr4:55152007-55152130:1;chr4:55152131-55153595:0;chr4:55153596-55153708:1;chr4:55153709-55154964:0;chr4:55154965-55155065:1;chr4:55155066-55155174:0;chr4:55155175-55155281:1;chr4:55155282-55156478:0;chr4:55156479-55156721:1;chr4:55156722-55524093:0;chr4:55524094-55524248:1;chr4:55524094-55603446:1;chr4:55524249-55561676:0;chr4:55561677-55561947:1;chr4:55561948-55564448:0;chr4:55564449-55564731:1;chr4:55564732-55565794:0;chr4:55565795-55565932:1;chr4:55565933-55569888:0;chr4:55569889-55570058:1;chr4:55570059-55573262:0;chr4:55573263-55573453:1;chr4:55573454-55575588:0;chr4:55575589-55575705:1;chr4:55575706-55589748:0;chr4:55589749-55589864:1;chr4:55589865-55592021:0;chr4:55592022-55592204:1;chr4:55592205-55593382:0;chr4:55593383-55593490:1;chr4:55593491-55593580:0;chr4:55593581-55593708:1;chr4:55593709-55593987:0;chr4:55593988-55594093:1;chr4:55594094-55594175:0;chr4:55594176-55594287:1;chr4:55594288-55595499:0;chr4:55595500-55595651:1;chr4:55595652-55597492:0;chr4:55597493-55597585:1;chr4:55597586-55598035:0;chr4:55598036-55598164:1;chr4:55598165-55599234:0;chr4:55599235-55599358:1;chr4:55599359-55602662:0;chr4:55602663-55602775:1;chr4:55602776-55602885:0;chr4:55602886-55602986:1;chr4:55602987-55603339:0;chr4:55603340-55603446:1;chr4:55603447-55948121:0;chr4:55948122-55948208:1;chr4:55948122-55987357:1;chr4:55948209-55948701:0;chr4:55948702-55948802:1;chr4:55948803-55964302:0;chr4:55964303-55964439:1;chr4:55964440-55964862:0;chr4:55964863-55964970:1;chr4:55964971-55968062:0;chr4:55968063-55968195:1;chr4:55968196-55968527:0;chr4:55968528-55968675:1;chr4:55968676-55970808:0;chr4:55970809-55971151:1;chr4:55971152-55971997:0;chr4:55971998-55972107:1;chr4:55972108-55972852:0;chr4:55972853-55972977:1;chr4:55972978-55973902:0;chr4:55973903-55974060:1;chr4:55974061-55976568:0;chr4:55976569-55976733:1;chr4:55976734-55976819:0;chr4:55976820-55976935:1;chr4:55976936-55979469:0;chr4:55979470-55979648:1;chr4:55979649-55980291:0;chr4:55980292-55980432:1;chr4:55980433-55981039:0;chr4:55981040-55981209:1;chr4:55981210-55981446:0;chr4:55981447-55981578:1;chr4:55981579-55984769:0;chr4:55984770-55984967:1;chr4:55984968-55987262:0;chr4:55987263-55987357:1;chr4:55987358-56212386:0;chr4:56212387-56212724:1;chr4:56212725-56225511:0;chr4:56225512-56225655:1;chr4:56225656-56230239:0;chr4:56230240-56230438:1;chr4:56230439-191154276:0;chr5:0-156184:0;chr5:1089096-1089243:-1;chr5:1089244-1093646:0;chr5:1093647-1093770:-1;chr5:1093771-1094267:0;chr5:1094268-1094363:-1;chr5:1094364-1111981:0;chr5:1111982-1112172:-1;chr5:1112173-1201708:0;chr5:1201709-1201967:-1;chr5:1201968-1208859:0;chr5:1208860-1209001:-1;chr5:1209002-1210557:0;chr5:1210558-1210696:-1;chr5:1210697-1212416:0;chr5:1212417-1212599:-1;chr5:1212600-1213576:0;chr5:1213577-1213688:-1;chr5:1213689-1214066:0;chr5:1214067-1214180:-1;chr5:1214181-1216671:0;chr5:1216672-1216801:-1;chr5:1216802-1216902:0;chr5:1216903-1217060:-1;chr5:1217061-1219016:0;chr5:1219017-1219222:-1;chr5:1219223-1219618:0;chr5:1219619-1219779:-1;chr5:1219780-1221264:0;chr5:1221265-1221428:-1;chr5:1221429-1225468:0;chr5:1225469-1225752:-1;chr5:1225753-1232864:0;chr5:1232865-1233003:-1;chr5:1233004-1235594:0;chr5:1235595-1235777:-1;chr5:1235778-1238063:0;chr5:1238064-1238175:-1;chr5:1238176-1239563:0;chr5:1239564-1239677:-1;chr5:1239678-1240644:0;chr5:1240645-1240774:-1;chr5:1240775-1242820:0;chr5:1242821-1242978:-1;chr5:1242979-1243668:0;chr5:1243669-1243874:-1;chr5:1243875-1244327:0;chr5:1244328-1244488:-1;chr5:1244489-1244721:0;chr5:1244722-1244882:-1;chr5:1244883-1253285:0;chr5:1253286-1253946:-1;chr5:1253947-1254481:0;chr5:1254482-1254620:-1;chr5:1254621-1255400:0;chr5:1255401-1255526:-1;chr5:1255527-1258711:0;chr5:1258712-1258774:-1;chr5:1258775-1260587:0;chr5:1260588-1260715:-1;chr5:1260716-1264517:0;chr5:1264518-1264707:-1;chr5:1264708-1266577:0;chr5:1266578-1266650:-1;chr5:1266651-1268633:0;chr5:1268634-1268748:-1;chr5:1268749-1271232:0;chr5:1271233-1271319:-1;chr5:1271320-1272298:0;chr5:1272299-1272395:-1;chr5:1272396-1278754:0;chr5:1278755-1278911:-1;chr5:1278912-1280271:0;chr5:1280272-1280453:-1;chr5:1280454-1282542:0;chr5:1282543-1282739:-1;chr5:1282740-1294884:0;chr5:1294885-1295162:-1;chr5:1295163-1321748:0;chr5:1321749-1321794:-1;chr5:1321795-1321877:0;chr5:1321878-1321934:-1;chr5:1321935-1322990:0;chr5:1322991-1323026:-1;chr5:1323027-1323900:0;chr5:1323901-1323984:-1;chr5:1323985-1324876:0;chr5:1324877-1324928:-1;chr5:1324929-1325864:0;chr5:1325865-1325931:-1;chr5:1325932-1330393:0;chr5:1330394-1330498:-1;chr5:1330499-1331912:0;chr5:1331913-1331998:-1;chr5:1331999-1334402:0;chr5:1334403-1334498:-1;chr5:1334499-1335170:0;chr5:1335171-1335289:-1;chr5:1335290-1338017:0;chr5:1338018-1338097:-1;chr5:1338098-1338973:0;chr5:1338974-1339120:-1;chr5:1339121-1341784:0;chr5:1341785-1341975:-1;chr5:1341976-1344464:0;chr5:1344465-1344566:-1;chr5:1344567-1344793:0;chr5:1344794-1345002:-1;chr5:1345003-1401028:0;chr5:1401029-1401101:-1;chr5:1401102-1403035:0;chr5:1403036-1403204:-1;chr5:1403205-1406301:0;chr5:1406302-1406403:-1;chr5:1406404-31534377:0;chr5:156185-156325:-1;chr5:156326-156886:0;chr5:156887-157026:-1;chr5:157027-161896:0;chr5:161897-162059:-1;chr5:162060-169453:0;chr5:169454-169707:-1;chr5:169708-171156:0;chr5:171157-171247:-1;chr5:171248-171327:0;chr5:171328-171559:-1;chr5:171560-173010:0;chr5:173011-173182:-1;chr5:173183-174031:0;chr5:174032-174213:-1;chr5:174214-181627:0;chr5:181628-181790:-1;chr5:181791-194821:0;chr5:194822-195468:-1;chr5:195469-204873:0;chr5:204874-206073:-1;chr5:206074-216842:0;chr5:216843-216974:-1;chr5:216975-218206:0;chr5:218207-218297:-1;chr5:218298-223595:0;chr5:223596-223683:-1;chr5:223684-224473:0;chr5:224474-224636:-1;chr5:224637-225532:0;chr5:225533-225677:-1;chr5:225678-225996:0;chr5:225997-226162:-1;chr5:226163-228298:0;chr5:228299-228448:-1;chr5:228449-230989:0;chr5:230990-231115:-1;chr5:231116-233590:0;chr5:233591-233760:-1;chr5:233761-235257:0;chr5:235258-235454:-1;chr5:235455-236541:0;chr5:236542-236714:-1;chr5:236715-240471:0;chr5:240472-240591:-1;chr5:240592-251105:0;chr5:251106-251218:-1;chr5:251219-251451:0;chr5:251452-251583:-1;chr5:251584-254506:0;chr5:254507-254621:-1;chr5:254622-256447:0;chr5:256448-256814:-1;chr5:256815-619103:0;chr5:31534378-31534524:-1;chr5:31534525-31535849:0;chr5:31535850-31536000:-1;chr5:31536001-31538365:0;chr5:31538366-31538796:-1;chr5:31538797-31541054:0;chr5:31541055-31541118:-1;chr5:31541119-31541386:0;chr5:31541387-31541509:-1;chr5:31541510-31799029:0;chr5:31799030-31799831:-1;chr5:31799832-31983259:0;chr5:31983260-31983762:-1;chr5:31983763-31995680:0;chr5:31995681-31995824:-1;chr5:31995825-32000243:0;chr5:32000244-32000377:-1;chr5:32000378-32010434:0;chr5:32010435-32010588:-1;chr5:32010589-32037335:0;chr5:32037336-32037448:-1;chr5:32037449-32048643:0;chr5:32048644-32048790:-1;chr5:32048791-32052715:0;chr5:32052716-32052836:-1;chr5:32052837-32053873:0;chr5:32053874-32053989:-1;chr5:32053990-32057759:0;chr5:32057760-32057834:-1;chr5:32057835-32057982:0;chr5:32057983-32058209:-1;chr5:32058210-32059343:0;chr5:32059344-32059462:-1;chr5:32059463-32061106:0;chr5:32061107-32061240:-1;chr5:32061241-32069673:0;chr5:32069674-32069756:-1;chr5:32069757-32071488:0;chr5:32071489-32071524:-1;chr5:32071525-32072265:0;chr5:32072266-32072423:-1;chr5:32072424-32073936:0;chr5:32073937-32074749:-1;chr5:32074750-32077566:0;chr5:32077567-32077712:-1;chr5:32077713-32087235:0;chr5:32087236-32091281:-1;chr5:32091282-32093011:0;chr5:32093012-32093130:-1;chr5:32093131-32097383:0;chr5:32097384-32097486:-1;chr5:32097487-32098468:0;chr5:32098469-32098740:-1;chr5:32098741-32101209:0;chr5:32101210-32101345:-1;chr5:32101346-32143853:0;chr5:32143854-32143986:-1;chr5:32143987-32173914:0;chr5:32173915-32174425:-1;chr5:32174426-32235066:0;chr5:32235067-32235235:-1;chr5:32235236-32239105:0;chr5:32239106-32239279:-1;chr5:32239280-32242161:0;chr5:32242162-32242233:-1;chr5:32242234-32243625:0;chr5:32243626-32243705:-1;chr5:32243706-32248106:0;chr5:32248107-32248232:-1;chr5:32248233-32248876:0;chr5:32248877-32248984:-1;chr5:32248985-32255797:0;chr5:32255798-32255874:-1;chr5:32255875-32263217:0;chr5:32263218-32263348:-1;chr5:32263349-32268805:0;chr5:32268806-32268900:-1;chr5:32268901-32270921:0;chr5:32270922-32271053:-1;chr5:32271054-32271937:0;chr5:32271938-32272011:-1;chr5:32272012-32274084:0;chr5:32274085-32274228:-1;chr5:32274229-32276786:0;chr5:32276787-32276848:-1;chr5:32276849-32312862:0;chr5:32312863-32313114:-1;chr5:32313115-32364052:0;chr5:32364053-32364151:-1;chr5:32364152-32364268:0;chr5:32364269-32364381:-1;chr5:32364382-32379219:0;chr5:32379220-32379316:-1;chr5:32379317-32380179:0;chr5:32380180-32380278:-1;chr5:32380279-32385612:0;chr5:32385613-32385755:-1;chr5:32385756-32387653:0;chr5:32387654-32387805:-1;chr5:32387806-32388573:0;chr5:32388574-32388780:-1;chr5:32388781-32390379:0;chr5:32390380-32390543:-1;chr5:32390544-32395263:0;chr5:32395264-32395410:-1;chr5:32395411-32397323:0;chr5:32397324-32397444:-1;chr5:32397445-32400110:0;chr5:32400111-32400308:-1;chr5:32400309-32403209:0;chr5:32403210-32403502:-1;chr5:32403503-32404009:0;chr5:32404010-32404202:-1;chr5:32404203-32406877:0;chr5:32406878-32407126:-1;chr5:32407127-32415072:0;chr5:32415073-32415292:-1;chr5:32415293-32417751:0;chr5:32417752-32417897:-1;chr5:32417898-32419924:0;chr5:32419925-32420208:-1;chr5:32420209-32444333:0;chr5:32444334-32444434:-1;chr5:32444435-32444726:0;chr5:32444727-32444844:-1;chr5:32444845-32585603:0;chr5:32585604-32585731:-1;chr5:32585732-32588616:0;chr5:32588617-32588690:-1;chr5:32588691-32591667:0;chr5:32591668-32591791:-1;chr5:32591792-32599065:0;chr5:32599066-32599175:-1;chr5:32599176-32710741:0;chr5:32710742-32710889:-1;chr5:32710890-32724802:0;chr5:32724803-32724926:-1;chr5:32724927-99463192:0;chr5:619104-619232:-1;chr5:619233-620182:0;chr5:620183-620376:-1;chr5:620377-624584:0;chr5:624585-624694:-1;chr5:624695-633882:0;chr5:633883-634062:-1;chr5:634063-635485:0;chr5:635486-635699:-1;chr5:635700-637630:0;chr5:637631-637933:-1;chr5:637934-639202:0;chr5:639203-639339:-1;chr5:639340-640521:0;chr5:640522-640719:-1;chr5:640720-644412:0;chr5:644413-644540:-1;chr5:644541-647918:0;chr5:647919-648031:-1;chr5:648032-653101:0;chr5:653102-653666:-1;chr5:653667-677863:0;chr5:677864-678179:-1;chr5:678180-693391:0;chr5:693392-693510:-1;chr5:693511-801213:0;chr5:801214-801279:-1;chr5:801280-814874:0;chr5:814875-814910:-1;chr5:814911-1089095:0;chr5:99463193-99463273:-1;chr5:99463274-99552399:0;chr5:99552400-99552684:-1;chr5:99552685-180915260:0;chr6:0-38840310:0;chr6:38840311-38840558:-1;chr6:38840559-38840680:0;chr6:38840681-38840923:-1;chr6:38840924-38841010:0;chr6:38841011-38841152:-1;chr6:38841153-38843365:0;chr6:38843366-38843604:-1;chr6:38843605-38850684:0;chr6:38850685-38850828:-1;chr6:38850829-38851096:0;chr6:38851097-38851232:-1;chr6:38851233-38851650:0;chr6:38851651-38851774:-1;chr6:38851775-38854565:0;chr6:38854566-38854780:-1;chr6:38854781-38858426:0;chr6:38858427-38858537:-1;chr6:38858538-38862475:0;chr6:38862476-38862640:-1;chr6:38862641-38863807:0;chr6:38863808-38864001:-1;chr6:38864002-38866032:0;chr6:38866033-38866156:-1;chr6:38866157-38867550:0;chr6:38867551-38867682:-1;chr6:38867683-38874028:0;chr6:38874029-38874183:-1;chr6:38874184-38875730:0;chr6:38875731-38875896:-1;chr6:38875897-38877292:0;chr6:38877293-38877520:-1;chr6:38877521-38879242:0;chr6:38879243-38879362:-1;chr6:38879363-38881623:0;chr6:38881624-38881728:-1;chr6:38881729-38882975:0;chr6:38882976-38883153:-1;chr6:38883154-42559887:0;chr6:42559888-42559967:-1;chr6:42559968-42561927:0;chr6:42561928-42562042:-1;chr6:42562043-42571324:0;chr6:42571325-42571456:-1;chr6:42571457-42573457:0;chr6:42573458-42573597:-1;chr6:42573598-42574325:0;chr6:42574326-42574389:-1;chr6:42574390-42579907:0;chr6:42579908-42580029:-1;chr6:42580030-42582807:0;chr6:42582808-42582916:-1;chr6:42582917-42583738:0;chr6:42583739-42583828:-1;chr6:42583829-42584976:0;chr6:42584977-42585076:-1;chr6:42585077-42585145:0;chr6:42585146-42585245:-1;chr6:42585246-42587204:0;chr6:42587205-42588089:-1;chr6:42588090-42600288:0;chr6:42600289-42600453:-1;chr6:42600454-42600541:0;chr6:42600542-42600642:-1;chr6:42600643-42603154:0;chr6:42603155-42603284:-1;chr6:42603285-42604747:0;chr6:42604748-42604932:-1;chr6:42604933-42607945:0;chr6:42607946-42608008:-1;chr6:42608009-42609318:0;chr6:42609319-42609430:-1;chr6:42609431-42610152:0;chr6:42610153-42610219:-1;chr6:42610220-42611950:0;chr6:42611951-42612074:-1;chr6:42612075-42612209:0;chr6:42612210-42612274:-1;chr6:42612275-42613202:0;chr6:42613203-42613328:-1;chr6:42613329-42615854:0;chr6:42615855-42615908:-1;chr6:42615909-42618020:0;chr6:42618021-42618124:-1;chr6:42618125-42619759:0;chr6:42619760-42619809:-1;chr6:42619810-42620227:0;chr6:42620228-42620383:-1;chr6:42620384-42623357:0;chr6:42623358-42623461:-1;chr6:42623462-42625760:0;chr6:42625761-42625871:-1;chr6:42625872-42625976:0;chr6:42625977-42626058:-1;chr6:42626059-42626382:0;chr6:42626383-42626562:-1;chr6:42626563-42627392:0;chr6:42627393-42627593:-1;chr6:42627594-42629920:0;chr6:42629921-42630015:-1;chr6:42630016-42630994:0;chr6:42630995-42631157:-1;chr6:42631158-42633145:0;chr6:42633146-42633250:-1;chr6:42633251-42633903:0;chr6:42633904-42633983:-1;chr6:42633984-42637828:0;chr6:42637829-42637978:-1;chr6:42637979-42638396:0;chr6:42638397-42638453:-1;chr6:42638454-42641527:0;chr6:42641528-42641625:-1;chr6:42641626-42641862:0;chr6:42641863-42641931:-1;chr6:42641932-42643792:0;chr6:42643793-42643929:-1;chr6:42643930-42644519:0;chr6:42644520-42644611:-1;chr6:42644612-42646275:0;chr6:42646276-42646407:-1;chr6:42646408-42647460:0;chr6:42647461-42647570:-1;chr6:42647571-42650791:0;chr6:42650792-42650849:-1;chr6:42650850-42652530:0;chr6:42652531-42652609:-1;chr6:42652610-42655952:0;chr6:42655953-42656124:-1;chr6:42656125-42657305:0;chr6:42657306-42657408:-1;chr6:42657409-42672101:0;chr6:42672102-42672349:-1;chr6:42672350-42689490:0;chr6:42689491-42690358:-1;chr6:42690359-42712232:0;chr6:42712233-42713884:-1;chr6:42713885-42788792:0;chr6:42788793-42788951:-1;chr6:42788952-42789754:0;chr6:42789755-42789801:-1;chr6:42789802-171115067:0;chr7:0-159138663:0;chr8:0-13080430:0;chr8:13080431-13080798:-1;chr8:13080799-35425614:0;chr8:35425615-35425759:-1;chr8:35425760-35453070:0;chr8:35453071-35453175:-1;chr8:35453176-35541063:0;chr8:35541064-35541245:-1;chr8:35541246-35542098:0;chr8:35542099-35542267:-1;chr8:35542268-35544061:0;chr8:35544062-35544227:-1;chr8:35544228-35563445:0;chr8:35563446-35563479:-1;chr8:35563480-35579726:0;chr8:35579727-35579913:-1;chr8:35579914-35583668:0;chr8:35583669-35584047:-1;chr8:35584048-35588528:0;chr8:35588529-35588614:-1;chr8:35588615-35606043:0;chr8:35606044-35606213:-1;chr8:35606214-35608098:0;chr8:35608099-35608327:-1;chr8:35608328-35616836:0;chr8:35616837-35616987:-1;chr8:35616988-35624418:0;chr8:35624419-35624584:-1;chr8:35624585-35631815:0;chr8:35631816-35631995:-1;chr8:35631996-36641840:0;chr8:36641841-36642123:-1;chr8:36642124-36644822:0;chr8:36644823-36644943:-1;chr8:36644944-36661543:0;chr8:36661544-36661606:-1;chr8:36661607-36662711:0;chr8:36662712-36662803:-1;chr8:36662804-36663785:0;chr8:36663786-36663898:-1;chr8:36663899-38089469:0;chr8:38089470-38089662:-1;chr8:38089663-38090503:0;chr8:38090504-38090732:-1;chr8:38090733-38091910:0;chr8:38091911-38092102:-1;chr8:38092103-38095054:0;chr8:38095055-38095145:-1;chr8:38095146-38097791:0;chr8:38097792-38097882:-1;chr8:38097883-38099766:0;chr8:38099767-38099903:-1;chr8:38099904-38103258:0;chr8:38103259-38103468:-1;chr8:38103469-38103749:0;chr8:38103750-38103818:-1;chr8:38103819-38105229:0;chr8:38105230-38105353:-1;chr8:38105354-38107224:0;chr8:38107225-38107321:-1;chr8:38107322-38109428:0;chr8:38109429-38109546:-1;chr8:38109547-38109648:0;chr8:38109649-38109805:-1;chr8:38109806-38110238:0;chr8:38110239-38110342:-1;chr8:38110343-38110473:0;chr8:38110474-38110645:-1;chr8:38110646-38111072:0;chr8:38111073-38111236:-1;chr8:38111237-38117556:0;chr8:38117557-38117665:-1;chr8:38117666-38123657:0;chr8:38123658-38123829:-1;chr8:38123830-38124496:0;chr8:38124497-38124909:-1;chr8:38124784-38124909:-1;chr8:38124910-38125413:0;chr8:38125414-38125478:-1;chr8:38125479-38125887:0;chr8:38125888-38125979:-1;chr8:38125980-38126398:0;chr8:38126399-38126508:-1;chr8:38126509-38126642:0;chr8:38126643-38126738:-1;chr8:38126739-38135822:0;chr8:38135823-38135930:-1;chr8:38135931-38137056:0;chr8:38137057-38137199:-1;chr8:38137200-38138983:0;chr8:38138984-38139101:-1;chr8:38139102-38146003:0;chr8:38146004-38146274:-1;chr8:38146275-38146909:0;chr8:38146910-38147023:-1;chr8:38147024-38147991:0;chr8:38147992-38148195:-1;chr8:38148196-38153312:0;chr8:38153313-38153470:-1;chr8:38153471-38156960:0;chr8:38156961-38157108:-1;chr8:38157109-38162103:0;chr8:38162104-38162275:-1;chr8:38162276-38162764:0;chr8:38162765-38162963:-1;chr8:38162964-38172163:0;chr8:38172164-38172291:-1;chr8:38172292-38172932:0;chr8:38172933-38173062:-1;chr8:38173063-38173428:0;chr8:38173429-38173560:-1;chr8:38173561-38176411:0;chr8:38176412-38176458:-1;chr8:38176459-38178588:0;chr8:38178589-38178690:-1;chr8:38178691-38184246:0;chr8:38184247-38184374:-1;chr8:38184375-38186894:0;chr8:38186895-38187411:-1;chr8:38187412-38188947:0;chr8:38188948-38189103:-1;chr8:38189104-38194821:0;chr8:38194822-38194985:-1;chr8:38194986-38196052:0;chr8:38196053-38196125:-1;chr8:38196126-38205013:0;chr8:38205014-38205733:-1;chr8:38205734-41364576:0;chr8:41364577-41364640:-1;chr8:41364641-41367101:0;chr8:41367102-41368499:-1;chr8:41368500-41386723:0;chr8:41386724-41386915:-1;chr8:41386916-41387701:0;chr8:41387702-41387817:-1;chr8:41387818-41393877:0;chr8:41393878-41393965:-1;chr8:41393966-41394697:0;chr8:41394698-41394812:-1;chr8:41394813-41397195:0;chr8:41397196-41397294:-1;chr8:41397295-41397433:0;chr8:41397434-41397523:-1;chr8:41397524-41399326:0;chr8:41399327-41399418:-1;chr8:41399419-41435705:0;chr8:41435706-41435797:-1;chr8:41435798-41466933:0;chr8:41466934-41467004:-1;chr8:41467005-41467172:0;chr8:41467173-41467474:-1;chr8:41467475-41468253:0;chr8:41468254-41468329:-1;chr8:41468330-41469420:0;chr8:41469421-41469511:-1;chr8:41469512-41469697:0;chr8:41469698-41469792:-1;chr8:41469793-41470362:0;chr8:41470363-41470479:-1;chr8:41470480-41471903:0;chr8:41471904-41471960:-1;chr8:41471961-41472480:0;chr8:41472481-41472567:-1;chr8:41472568-41476201:0;chr8:41476202-41476331:-1;chr8:41476332-41476415:0;chr8:41476416-41476496:-1;chr8:41476497-41503827:0;chr8:41503828-41504213:-1;chr8:41504214-41504711:0;chr8:41504712-41504878:-1;chr8:41504879-41519317:0;chr8:41519318-41519459:-1;chr8:41519460-41573168:0;chr8:41573169-41573367:-1;chr8:41573368-41574469:0;chr8:41574470-41574569:-1;chr8:41574570-41575120:0;chr8:41575121-41575220:-1;chr8:41575221-41575622:0;chr8:41575623-41575722:-1;chr8:41575723-41577177:0;chr8:41577178-41577376:-1;chr8:41577377-41580641:0;chr8:41580642-41580741:-1;chr8:41580742-41581051:0;chr8:41581052-41581151:-1;chr8:41581152-41581972:0;chr8:41581973-41582072:-1;chr8:41582073-41584766:0;chr8:41584767-41584866:-1;chr8:41584867-41585424:0;chr8:41585425-41585524:-1;chr8:41585525-41591487:0;chr8:41591488-41591587:-1;chr8:41591588-41615552:0;chr8:41615553-41615655:-1;chr8:41615656-41655028:0;chr8:41655029-41655140:-1;chr8:41655141-41798358:0;chr8:41798359-41798962:-1;chr8:41798963-41800309:0;chr8:41800310-41800518:-1;chr8:41800519-41801264:0;chr8:41801265-41801497:-1;chr8:41801498-41804107:0;chr8:41804108-41804202:-1;chr8:41804203-41805267:0;chr8:41805268-41805430:-1;chr8:41805431-41806738:0;chr8:41806739-41806881:-1;chr8:41806882-41812812:0;chr8:41812813-41812929:-1;chr8:41812930-41832220:0;chr8:41832221-41832340:-1;chr8:41832341-41834524:0;chr8:41834525-41834845:-1;chr8:41834846-41836158:0;chr8:41836159-41836295:-1;chr8:41836296-41838362:0;chr8:41838363-41838445:-1;chr8:41838446-41839355:0;chr8:41839356-41839472:-1;chr8:41839473-41844971:0;chr8:41844972-41845081:-1;chr8:41845082-41905894:0;chr8:41905895-41906820:-1;chr8:41906821-42179412:0;chr8:42179413-42179463:-1;chr8:42179464-42179570:0;chr8:42179571-42179671:-1;chr8:42179672-42179863:0;chr8:42179864-42180012:-1;chr8:42180013-42183486:0;chr8:42183487-42183615:-1;chr8:42183616-42186640:0;chr8:42186641-42186732:-1;chr8:42186733-42196528:0;chr8:42196529-42196587:-1;chr8:42196588-42202469:0;chr8:42202470-42202537:-1;chr8:42202538-42206532:0;chr8:42206533-42206608:-1;chr8:42206609-42207523:0;chr8:42207524-42207583:-1;chr8:42207584-42210035:0;chr8:42210036-42210086:-1;chr8:42210087-42213032:0;chr8:42213033-42213085:-1;chr8:42213086-42214685:0;chr8:42214686-42214741:-1;chr8:42214742-42214836:0;chr8:42214837-42214910:-1;chr8:42214911-42218811:0;chr8:42218812-42218883:-1;chr8:42218884-42220128:0;chr8:42220129-42220216:-1;chr8:42220217-42226787:0;chr8:42226788-42226853:-1;chr8:42226854-42227365:0;chr8:42227366-42227506:-1;chr8:42227507-42977248:0;chr8:42977249-42978323:-1;chr8:42978324-43002089:0;chr8:43002090-43002206:-1;chr8:43002207-43013716:0;chr8:43013717-43013854:-1;chr8:43013855-43014064:0;chr8:43014065-43014187:-1;chr8:43014188-43016579:0;chr8:43016580-43016650:-1;chr8:43016651-43024314:0;chr8:43024315-43024385:-1;chr8:43024386-43025726:0;chr8:43025727-43025837:-1;chr8:43025838-43027451:0;chr8:43027452-43027529:-1;chr8:43027530-43028854:0;chr8:43028855-43028886:-1;chr8:43028887-43033215:0;chr8:43033216-43033377:-1;chr8:43033378-43037286:0;chr8:43037287-43037403:-1;chr8:43037404-43046615:0;chr8:43046616-43046738:-1;chr8:43046739-43047445:0;chr8:43047446-43047573:-1;chr8:43047574-43048898:0;chr8:43048899-43048986:-1;chr8:43048987-43052089:0;chr8:43052090-43052168:-1;chr8:43052169-43052813:0;chr8:43052814-43052885:-1;chr8:43052886-43052981:0;chr8:43052982-43053095:-1;chr8:43053096-43147583:0;chr8:43147584-43147926:-1;chr8:43147927-43152161:0;chr8:43152162-43152277:-1;chr8:43152278-43152427:0;chr8:43152428-43152602:-1;chr8:43152603-43155659:0;chr8:43155660-43155767:-1;chr8:43155768-43157114:0;chr8:43157115-43157253:-1;chr8:43157254-43159840:0;chr8:43159841-43159912:-1;chr8:43159913-43171032:0;chr8:43171033-43171104:-1;chr8:43171105-43172495:0;chr8:43172496-43172541:-1;chr8:43172542-43173597:0;chr8:43173598-43173765:-1;chr8:43173766-43197020:0;chr8:43197021-43197052:-1;chr8:43197053-43197328:0;chr8:43197329-43197471:-1;chr8:43197472-43211900:0;chr8:43211901-43212115:-1;chr8:43212116-43216184:0;chr8:43216185-43216309:-1;chr8:43216310-146364022:0;chr9:0-2831249:0;chr9:13150509-13150687:1;chr9:13150688-13158015:0;chr9:13158016-13158109:1;chr9:13158110-13162688:0;chr9:13162689-13162794:1;chr9:13162795-13168363:0;chr9:13168364-13168563:1;chr9:13168564-13175749:0;chr9:13175750-13175874:1;chr9:13175875-13176133:0;chr9:13176134-13176416:1;chr9:13176417-13183415:0;chr9:13183416-13183584:1;chr9:13183585-13186267:0;chr9:13186268-13186385:1;chr9:13186386-13188781:0;chr9:13188782-13188992:1;chr9:13188993-13190111:0;chr9:13190112-13190298:1;chr9:13190299-13192128:0;chr9:13192129-13192294:1;chr9:13192295-13193164:0;chr9:13193165-13193312:1;chr9:13193313-13196118:0;chr9:13196119-13196229:1;chr9:13196230-13205033:0;chr9:13205034-13205106:1;chr9:13205107-13205913:0;chr9:13205914-13206098:1;chr9:13206099-13216771:0;chr9:13216772-13216861:1;chr9:13216862-13217177:0;chr9:13217178-13217293:1;chr9:13217294-13219556:0;chr9:13219557-13219767:1;chr9:13219768-13221369:0;chr9:13221370-13221499:1;chr9:13221500-13222230:0;chr9:13222231-13222445:1;chr9:13222446-13223568:0;chr9:13223569-13223709:1;chr9:13223710-13224371:0;chr9:13224372-13224582:1;chr9:13224583-13247632:0;chr9:13247633-13247800:1;chr9:13247801-13250297:0;chr9:13250298-13250371:1;chr9:13250372-13279397:0;chr9:13279398-13279563:1;chr9:13279564-14112996:0;chr9:14112997-14113080:1;chr9:14112997-14398982:1;chr9:14113081-14116205:0;chr9:14116206-14116345:1;chr9:14116346-14120437:0;chr9:14120438-14120623:1;chr9:14120624-14125629:0;chr9:14125630-14125765:1;chr9:14125766-14146686:0;chr9:14146687-14146806:1;chr9:14146807-14150142:0;chr9:14150143-14150264:1;chr9:14150265-14155822:0;chr9:14155823-14155892:1;chr9:14155893-14179724:0;chr9:14179725-14179779:1;chr9:14179780-14306986:0;chr9:14306987-14307519:1;chr9:14307520-14398521:0;chr9:14398522-14398982:1;chr9:14398983-14619635:0;chr9:14619636-14619680:1;chr9:14619681-14639892:0;chr9:14639893-14640010:1;chr9:14640011-14658745:0;chr9:14658746-14658885:1;chr9:14658886-14662211:0;chr9:14662212-14662324:1;chr9:14662325-14672826:0;chr9:14672827-14672926:1;chr9:14672927-14674183:0;chr9:14674184-14674383:1;chr9:14674384-16727793:0;chr9:16727794-16727995:1;chr9:16727996-16738356:0;chr9:16738357-16738483:1;chr9:16738484-16870642:0;chr9:16870643-16870786:1;chr9:16870787-17143284:0;chr9:17143285-17143374:1;chr9:17143375-17226199:0;chr9:17226200-17226285:1;chr9:17226286-17235654:0;chr9:17235655-17235790:1;chr9:17235791-17236405:0;chr9:17236406-17236586:1;chr9:17236587-17273729:0;chr9:17273730-17273864:1;chr9:17273865-17298186:0;chr9:17298187-17298350:1;chr9:17298351-17309054:0;chr9:17309055-17309250:1;chr9:17309251-17330628:0;chr9:17330629-17330806:1;chr9:17330807-17332601:0;chr9:17332602-17332728:1;chr9:17332729-17340823:0;chr9:17340824-17340946:1;chr9:17340947-17342321:0;chr9:17342322-17342442:1;chr9:17342443-17366613:0;chr9:17366614-17366715:1;chr9:17366716-17388158:0;chr9:17388159-17388251:1;chr9:17388252-17394530:0;chr9:17394531-17395067:1;chr9:17395068-17409289:0;chr9:17409290-17409471:1;chr9:17409472-17415784:0;chr9:17415785-17415879:1;chr9:17415880-17415962:0;chr9:17415963-17416187:1;chr9:17416188-17457520:0;chr9:17457521-17457713:1;chr9:17457714-17462912:0;chr9:17462913-17463011:1;chr9:17463012-17464493:0;chr9:17464494-17464621:1;chr9:17464622-17465977:0;chr9:17465978-17466116:1;chr9:17466117-17466702:0;chr9:17466703-17466889:1;chr9:17466890-19622257:0;chr9:19622258-19622297:1;chr9:19622298-19785933:0;chr9:19785934-19787017:1;chr9:19787018-20353521:0;chr9:20353522-20353594:1;chr9:20353522-20622514:1;chr9:20353595-20354804:0;chr9:20354805-20354877:1;chr9:20354878-20360738:0;chr9:20360739-20360839:1;chr9:20360840-20363472:0;chr9:20363473-20363603:1;chr9:20363604-20365665:0;chr9:20365666-20365742:1;chr9:20365743-20413717:0;chr9:20413718-20414423:1;chr9:20414424-20448119:0;chr9:20448120-20448264:1;chr9:20448265-20456700:0;chr9:20456701-20456784:1;chr9:20456785-20620651:0;chr9:20620652-20620833:1;chr9:20620834-20622242:0;chr9:20622243-20622514:1;chr9:20622515-20658307:0;chr9:20658308-20658458:1;chr9:20658308-20993327:1;chr9:20658459-20658688:0;chr9:20658689-20658825:1;chr9:20658826-20694517:0;chr9:20694518-20694563:1;chr9:20694564-20715319:0;chr9:20715320-20715409:1;chr9:20715410-20717791:0;chr9:20717792-20717867:1;chr9:20717868-20720377:0;chr9:20720378-20720533:1;chr9:20720534-20740233:0;chr9:20740234-20740339:1;chr9:20740340-20758087:0;chr9:20758088-20758190:1;chr9:20758191-20764866:0;chr9:20764867-20765072:1;chr9:20765073-20770029:0;chr9:20770030-20770237:1;chr9:20770238-20778678:0;chr9:20778679-20778767:1;chr9:20778768-20781724:0;chr9:20781725-20781928:1;chr9:20781929-20789348:0;chr9:20789349-20789607:1;chr9:20789608-20819793:0;chr9:20819794-20819899:1;chr9:20819900-20820321:0;chr9:20820322-20820424:1;chr9:20820425-20820938:0;chr9:20820939-20821070:1;chr9:20821071-20822986:0;chr9:20822987-20823114:1;chr9:20823115-20862575:0;chr9:20862576-20862711:1;chr9:20862712-20865923:0;chr9:20865924-20865975:1;chr9:20865976-20866926:0;chr9:20866927-20867011:1;chr9:20867012-20874678:0;chr9:20874679-20874806:1;chr9:20874807-20881868:0;chr9:20881869-20882055:1;chr9:20882056-20885106:0;chr9:20885107-20885229:1;chr9:20885230-20907147:0;chr9:20907148-20907241:1;chr9:20907242-20912863:0;chr9:20912864-20912953:1;chr9:20912954-20916890:0;chr9:20916891-20916936:1;chr9:20916937-20923657:0;chr9:20923658-20923767:1;chr9:20923768-20926298:0;chr9:20926299-20926416:1;chr9:20926417-20929355:0;chr9:20929356-20929595:1;chr9:20929596-20933011:0;chr9:20933012-20933102:1;chr9:20933103-20944624:0;chr9:20944625-20944773:1;chr9:20944774-20946698:0;chr9:20946699-20946819:1;chr9:20946820-20948268:0;chr9:20948269-20948392:1;chr9:20948393-20948848:0;chr9:20948849-20948927:1;chr9:20948928-20949601:0;chr9:20949602-20949674:1;chr9:20949675-20950993:0;chr9:20950994-20951097:1;chr9:20951098-20952982:0;chr9:20952983-20953064:1;chr9:20953065-20976417:0;chr9:20976418-20976547:1;chr9:20976548-20978336:0;chr9:20978337-20978453:1;chr9:20978454-20981423:0;chr9:20981424-20981685:1;chr9:20981686-20982354:0;chr9:20982355-20982445:1;chr9:20982446-20986285:0;chr9:20986286-20986464:1;chr9:20986465-20988329:0;chr9:20988330-20988428:1;chr9:20988429-20990120:0;chr9:20990121-20990373:1;chr9:20990374-20993250:0;chr9:20993251-20993327:1;chr9:20993328-21008018:0;chr9:21008019-21008145:1;chr9:21008019-21031635:1;chr9:21008146-21011586:0;chr9:21011587-21011694:1;chr9:21011695-21015895:0;chr9:21015896-21016009:1;chr9:21016010-21026593:0;chr9:21026594-21026722:1;chr9:21026723-21029292:0;chr9:21029293-21029397:1;chr9:21029398-21031550:0;chr9:21031551-21031635:1;chr9:21031636-21077102:0;chr9:21077103-21077943:1;chr9:21077944-21140629:0;chr9:21140630-21142144:1;chr9:21142145-21165634:0;chr9:21165635-21166659:1;chr9:21166660-21186616:0;chr9:21186617-21187598:1;chr9:21187599-21201466:0;chr9:21201467-21202204:1;chr9:21202205-21206178:0;chr9:21206179-21207142:1;chr9:21207143-21216370:0;chr9:21216371-21217310:1;chr9:21217311-21227240:0;chr9:21227241-21228221:1;chr9:21228222-21239199:0;chr9:21239200-21239978:1;chr9:21239979-21304611:0;chr9:21304612-21305312:1;chr9:21305313-21350315:0;chr9:21350316-21350886:1;chr9:21350887-21367369:0;chr9:21367370-21368075:1;chr9:21368076-21384252:0;chr9:21384253-21385396:1;chr9:21385397-21409144:0;chr9:21409145-21410184:1;chr9:21410185-21440451:0;chr9:21440452-21441315:1;chr9:21441316-21480837:0;chr9:21480838-21482312:1;chr9:21482313-77370267:0;chr9:2831250-2831344:1;chr9:2831345-2833355:0;chr9:2833356-2833432:1;chr9:2833433-2834029:0;chr9:2834030-2834166:1;chr9:2834167-2837178:0;chr9:2837179-2837401:1;chr9:2837402-2838424:0;chr9:2838425-2838517:1;chr9:2838518-2844043:0;chr9:2844044-2844130:1;chr9:2844131-3224645:0;chr9:3224646-3225280:1;chr9:3225281-3228845:0;chr9:3228846-3228889:1;chr9:3228890-3248030:0;chr9:3248031-3248185:1;chr9:3248186-3256989:0;chr9:3256990-3257199:1;chr9:3257200-3262933:0;chr9:3262934-3263084:1;chr9:3263085-3266206:0;chr9:3266207-3266305:1;chr9:3266306-3270369:0;chr9:3270370-3270525:1;chr9:3270526-3271001:0;chr9:3271002-3271118:1;chr9:3271119-3275498:0;chr9:3275499-3275612:1;chr9:3275613-3277338:0;chr9:3277339-3277461:1;chr9:3277462-3288129:0;chr9:3288130-3288250:1;chr9:3288251-3293075:0;chr9:3293076-3293258:1;chr9:3293259-3301544:0;chr9:3301545-3301620:1;chr9:3301621-3330257:0;chr9:3330258-3330517:1;chr9:3330518-3346665:0;chr9:3346666-3346764:1;chr9:3346765-8484117:0;chr9:77370268-77370389:-1;chr9:77370390-77376913:0;chr9:77376914-77378050:-1;chr9:77378051-77386617:0;chr9:77386618-77386751:-1;chr9:77386752-77390797:0;chr9:77390798-77390992:-1;chr9:77390993-77397276:0;chr9:77397277-77397392:-1;chr9:77397393-77397593:0;chr9:77397594-77397769:-1;chr9:77397770-77400788:0;chr9:77400789-77401041:-1;chr9:77401042-77403528:0;chr9:77403529-77403658:-1;chr9:77403659-77407538:0;chr9:77407539-77407686:-1;chr9:77407687-77411655:0;chr9:77411656-77411809:-1;chr9:77411810-77415168:0;chr9:77415169-77415398:-1;chr9:77415399-77416812:0;chr9:77416813-77417091:-1;chr9:77417092-77418708:0;chr9:77418709-77418802:-1;chr9:77418803-77422948:0;chr9:77422949-77423090:-1;chr9:77423091-77425729:0;chr9:77425730-77425784:-1;chr9:77425785-77427213:0;chr9:77427214-77427349:-1;chr9:77427350-77431583:0;chr9:77431584-77431685:-1;chr9:77431686-77431806:0;chr9:77431807-77431880:-1;chr9:77431881-77435218:0;chr9:77435219-77435343:-1;chr9:77435344-77436583:0;chr9:77436584-77436753:-1;chr9:77436754-77442692:0;chr9:77442693-77442865:-1;chr9:77442866-77448912:0;chr9:77448913-77449038:-1;chr9:77449039-77454938:0;chr9:77454939-77455153:-1;chr9:77455154-77457080:0;chr9:77457081-77457259:-1;chr9:77457260-77470441:0;chr9:77470442-77470481:-1;chr9:77470482-77473583:0;chr9:77473584-77473664:-1;chr9:77473665-79814859:0;chr9:79814860-79814904:-1;chr9:79814905-79816279:0;chr9:79816280-79816323:-1;chr9:79816324-79820227:0;chr9:79820228-79820324:-1;chr9:79820325-79820892:0;chr9:79820893-79820995:-1;chr9:79820996-79824337:0;chr9:79824338-79824448:-1;chr9:79824449-79825530:0;chr9:79825531-79825591:-1;chr9:79825592-79827883:0;chr9:79827884-79827944:-1;chr9:79827945-79828148:0;chr9:79828149-79828230:-1;chr9:79828231-79829243:0;chr9:79829244-79829302:-1;chr9:79829303-79834868:0;chr9:79834869-79834997:-1;chr9:79834998-79835191:0;chr9:79835192-79835299:-1;chr9:79835300-79836099:0;chr9:79836100-79836272:-1;chr9:79836273-79840840:0;chr9:79840841-79840904:-1;chr9:79840905-79841380:0;chr9:79841381-79841514:-1;chr9:79841515-79842305:0;chr9:79842306-79842401:-1;chr9:79842402-79843036:0;chr9:79843037-79843180:-1;chr9:79843181-79852916:0;chr9:79852917-79853107:-1;chr9:79853108-79867149:0;chr9:79867150-79867268:-1;chr9:79867269-79875000:0;chr9:79875001-79875140:-1;chr9:79875141-79888194:0;chr9:79888195-79888280:-1;chr9:79888281-79890412:0;chr9:79890413-79890568:-1;chr9:79890569-79890979:0;chr9:79890980-79891137:-1;chr9:79891138-79895073:0;chr9:79895074-79895154:-1;chr9:79895155-79896781:0;chr9:79896782-79896842:-1;chr9:79896843-79897035:0;chr9:79897036-79897190:-1;chr9:79897191-79898269:0;chr9:79898270-79898387:-1;chr9:79898388-79898461:0;chr9:79898462-79898566:-1;chr9:79898567-79908255:0;chr9:79908256-79908424:-1;chr9:79908425-79910456:0;chr9:79910457-79910762:-1;chr9:79910763-79917829:0;chr9:79917830-79917978:-1;chr9:79917979-79922859:0;chr9:79922860-79923014:-1;chr9:79923015-79928906:0;chr9:79928907-79929035:-1;chr9:79929036-79929409:0;chr9:79929410-79929580:-1;chr9:79929581-79930167:0;chr9:79930168-79930386:-1;chr9:79930387-79931088:0;chr9:79931089-79931322:-1;chr9:79931323-79932520:0;chr9:79932521-79932614:-1;chr9:79932615-79933149:0;chr9:79933150-79933507:-1;chr9:79933508-79934486:0;chr9:79934487-79934589:-1;chr9:79934590-79936083:0;chr9:79936084-79936243:-1;chr9:79936244-79936405:0;chr9:79936406-79936662:-1;chr9:79936663-79937981:0;chr9:79937982-79938143:-1;chr9:79938144-79946924:0;chr9:79946925-79947029:-1;chr9:79947030-98703593:0;chr9:8484118-8484378:1;chr9:8484379-8485225:0;chr9:8485226-8485324:1;chr9:8485325-8485760:0;chr9:8485761-8486349:1;chr9:8486350-8492860:0;chr9:8492861-8492979:1;chr9:8492980-8497240:0;chr9:8497241-8497268:1;chr9:8497269-8499645:0;chr9:8499646-8499840:1;chr9:8499841-8500752:0;chr9:8500753-8501059:1;chr9:8501060-8504259:0;chr9:8504260-8504405:1;chr9:8504406-8507299:0;chr9:8507300-8507434:1;chr9:8507435-8517846:0;chr9:8517847-8518429:1;chr9:8518430-8521275:0;chr9:8521276-8521546:1;chr9:8521547-8523511:0;chr9:8523512-8523524:1;chr9:8523525-8524923:0;chr9:8524924-8525035:1;chr9:8525036-8526625:0;chr9:8526626-8526644:1;chr9:8526645-8527343:0;chr9:8527344-8527353:1;chr9:8527354-8528589:0;chr9:8528590-8528779:1;chr9:8528780-8633315:0;chr9:8633316-8633458:1;chr9:8633459-8636697:0;chr9:8636698-8636844:1;chr9:8636845-13150508:0;chr9:98703594-98703826:-1;chr9:98703827-98709522:0;chr9:98709523-98709751:-1;chr9:98709752-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 Background: Osteosarcoma (OS) is a prevalent primary malignant bone tumour with unknown etiology. These highly metastasizing tumours are among the most frequent causes of cancer-related deaths. Thus, there is an urgent need for different markers, and with our study, we were aiming towards finding novel biomarkers for OS. Methods: For that, we analysed the whole exome of the tumorous and non-tumour bone tissue from the same patient with OS applying next-generation sequencing. For data analysis, we used several softwares and combined the exome data with RNA-seq data from our previous study. Results: In the tumour exome, we found wide genomic rearrangements, which should qualify as chromotripsis-we detected almost 3,000 somatic single nucleotide variants (SNVs) and small indels and more than 2,000 copy number variants (CNVs) in different chromosomes. Furthermore, the somatic changes seem to be associated to bone tumours, whereas germline mutations to cancer in general. We confirmed the previous findings that the most significant pathway involved in OS pathogenesis is probably the WNT/beta-catenin signalling pathway. Also, the IGF1/ IGF2 and IGF1R homodimer signalling and TP53 (including downstream tumour suppressor gene EI24) pathways may have a role. Additionally, the mucin family genes, especially MUC4 and cell cycle controlling gene CDC27 may be considered as potential biomarkers for OS. Conclusions: The genes, in which the mutations were detected, may be considered as targets for finding biomarkers for OS. As the study is based on a single case and only DNA and RNA analysis, further confirmative studies are required. GRCh37/hg19 NA CTDB0352 Research 23139213 Cazes A, Louis-Brennetot C, Mazot P, Dingli F, Lombard B, Boeva V, Daveau R, Cappo J, Combaret V, Schleiermacher G, Jouannet S, Ferrand S, Pierron G, Barillot E, Loew D, Vigny M, Delattre O, Janoueix-Lerosey I Characterization of rearrangements involving the ALK gene reveals a novel truncated form associated with tumor aggressiveness in neuroblastoma Cancer Research 2013 Jan 2,3 Neuroblastoma Next Generation Sequencing Homo sapiens CLB-Re Illumina Genome Analyzer II chr10:0-135374737:0;chr11:0-134452384:0;chr12:0-132349534:0;chr13:0-114142980:0;chr14:0-106368585:0;chr15:0-100338915:0;chr16:0-88827254:0;chr17:0-78774742:0;chr18:0-76117153:0;chr19:0-63811651:0;chr1:0-247249719:0;chr20:0-62435964:0;chr21:0-46944323:0;chr22:0-49691432:0;chr2:0-29344475:0;chr2:29344476-33156045:-1;chr2:29603903-42009571:-1;chr2:29646730-36893802:-1;chr2:42009572-242951149:0;chr3:0-199501827:0;chr4:0-191273063:0;chr5:0-180857866:0;chr6:0-170899992:0;chr7:0-158821424:0;chr8:0-146274826:0;chr9:0-140273252:0;chrX:0-154913754:0;chrY:0-57772954:0 hs2:29344476-29344476,hs2:33156045-33156045;hs2:29603903-29603903,hs2:42009571-42009571;hs2:29646730-29646730,hs2:36893802-36893802;hs2:29423161-29423161,hs3:65157963-65157963;hs2:29557752-29557752,hs3:74605412-74605412;hs2:29346060-29346060,hs3:61180791-61180791 ALK;LTBP1;VIT; Inserm U830, Institut Curie, Centre de Recherche, Paris, France Activating mutations of the ALK gene have been identified in sporadic and familial cases of neuroblastoma (NB), a cancer of the peripheral nervous system, and are thought to be the primary mechanism of oncogenic activation of this receptor in this pediatric neoplasm. To address the possibility that ALK activation may occur through genomic rearrangements as detected in other cancers, we first took advantage of high-resolution arraycomparative genomic hybridization to search for ALK rearrangements in NB samples. Using complementary experiments by capture/paired-end sequencing and FISH experiments, various types of rearrangements were fully characterized, including partial gains or amplifications, in several NB cell lines and primary tumors. In the CLB-Bar cell line, we described a genomic rearrangement associated with an amplification of the ALK locus, leading to the expression of a 170 kDa protein lacking part of the extracellular domain encoded by exons 4 to 11, named ALKD4-11. Analysis of genomic DNA from the tumor at diagnosis and relapse revealed that the ALK gene was amplified at diagnosis but that the rearranged ALK allele was observed at the relapse stage only, suggesting that it may be implicated in tumor aggressiveness. Consistently, oncogenic and tumorigenic properties of the ALKD4-11 variant were shown after stable expression in NIH3T3 cells. Moreover, we documented an increased constitutive kinase activity of this variant, as well as an impaired maturation and retention into intracellular compartments. These results indicate that genomic rearrangements constitute an alternative mechanism to ALK point mutations resulting in receptor activation. NCBI 36/hg18 Yes ALK,CNTN3;ALK,FHIT;ALK,LTBP1;ALK,VIT CTDB0354 Research 24147068 Wei JS, Johansson P, Chen L, Song YK, Tolman C, Li S, Hurd L, Patidar R, Wen X, Badgett TC, Cheuk AT, Marshall JC, Steeg PS, Vaque Diez JP, Yu Y, Gutkind JS, Khan J Massively parallel sequencing reveals an accumulation of de novo mutations and an activating mutation of LPAR1 in a patient with metastatic neuroblastoma PLoS One 2013 Oct 1,4,13 Neuroblastoma Next Generation Sequencing Homo sapiens Met2 Complete Genomics chr10:0-66751984:0;chr10:66751985-66789278:1;chr10:66789279-135534747:0;chr11:0-135006516:0;chr12:0-133577764:0;chr12:133577765-133630336:1;chr12:133630337-133851895:0;chr13:0-43207210:0;chr13:43207211-45534853:1;chr13:43312476-44870674:1;chr13:45534854-115169878:0;chr14:0-26468519:0;chr14:26468520-27412468:1;chr14:27412469-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-38535209:0;chr17:38535210-38696124:1;chr17:38696125-81195210:0;chr18:0-78077248:0;chr19:0-46304183:0;chr19:46304184-46362265:1;chr19:46362266-59128983:0;chr1:0-19684671:0;chr1:19684672-45527083:1;chr1:21258729-36939067:1;chr1:23118056-33564477:1;chr1:25684105-30354775:-1;chr1:29102259-34772072:-1;chr1:34472642-76565404:-1;chr1:76565405-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-19499749:0;chr22:19499750-19707873:1;chr22:19707874-51304566:0;chr2:0-79090239:0;chr2:79090240-79706333:1;chr2:79706334-243199373:0;chr3:0-198022430:0;chr4:0-62315268:0;chr4:62315269-66379523:1;chr4:66379524-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-8772565:0;chr7:8772566-91744804:1;chr7:91744805-159138663:0;chr8:0-73803609:0;chr8:73803610-73803665:1;chr8:73803666-146364022:0;chr9:0-141213431:0;chrX:0-76916705:0;chrX:76916706-76932438:-1;chrX:76932439-155270560:0;chrY:0-59373566:0 hs1:15709415-15709415,hs1:38462152-38462152;hs1:21588867-21588867,hs1:31216791-31216791;hs1:22778291-22778291,hs1:23118846-23118846;hs1:22778291-22778291,hs1:34817224-34817224;hs1:24633158-24633158,hs1:45523914-45523914;hs1:29195642-29195642,hs1:85959093-85959093;hs1:29801030-29801030,hs1:43429062-43429062;hs1:91853148-91853148,hsX:108297835-108297835;hs1:113835948-113835948,hs1:150053653-150053653;hs1:113841722-113841722,hs4:68112150-68112150;hs1:113842344-113842344,hs4:68106267-68106267;hs1:113842677-113842677,hs4:62591576-62591576;hs1:113842740-113842740,hs4:62013582-62013582;hs1:113843257-113843257,hs4:68100833-68100833;hs1:113843282-113843282,hs4:66377763-66377763;hs1:113843298-113843298,hs4:65359600-65359600;hs1:113843411-113843411,hs4:62337136-62337136;hs1:113844354-113844354,hs4:66483003-66483003;hs1:113928797-113928797,hs4:68115985-68115985;hs1:113929632-113929632,hsX:88386784-88386784;hs1:113929764-113929764,hs4:62017959-62017959;hs1:113931614-113931614,hs4:68106604-68106604;hs1:113932103-113932103,hs1:150062096-150062096;hs1:113933436-113933436,hs1:150008218-150008218;hs1:113934553-113934553,hs4:62057325-62057325;hs1:113935655-113935655,hs1:150001425-150001425;hs1:113936130-113936130,hs4:65653764-65653764;hs1:113937594-113937594,hs4:62590597-62590597;hs1:113940793-113940793,hs4:62849618-62849618;hs1:113943479-113943479,hs1:114050846-114050846;hs1:113943660-113943660,hsX:88443338-88443338;hs1:113945298-113945298,hs4:66414608-66414608;hs1:113945397-113945397,hs4:62450837-62450837;hs1:113945941-113945941,hs4:62013440-62013440;hs1:113946026-113946026,hs1:150082718-150082718;hs1:113947399-113947399,hs4:66376686-66376686;hs1:113950971-113950971,hs4:62642505-62642505;hs1:113952218-113952218,hs4:68112287-68112287;hs1:113952548-113952548,hs4:66469482-66469482;hs1:113952775-113952775,hs4:62385455-62385455;hs1:113957585-113957585,hs1:150123509-150123509;hs1:113958567-113958567,hs4:68099716-68099716;hs1:114025815-114025815,hs4:62743097-62743097;hs1:114047339-114047339,hs1:115144218-115144218;hs1:114757940-114757940,hs4:66374994-66374994;hs1:114768743-114768743,hs4:65655134-65655134;hs1:114769641-114769641,hs4:68099839-68099839;hs1:115140410-115140410,hs4:62628181-62628181;hs1:115142025-115142025,hs4:62681547-62681547;hs1:115142684-115142684,hs4:68101875-68101875;hs1:115143745-115143745,hs4:62329357-62329357;hs1:115144218-115144218,hs1:150016216-150016216;hs1:115144218-115144218,hs4:65361603-65361603;hs1:115144237-115144237,hs4:65363110-65363110;hs1:115145868-115145868,hs4:68107760-68107760;hs1:115147404-115147404,hs4:62007917-62007917;hs1:115147404-115147404,hs4:66383970-66383970;hs1:115148786-115148786,hs4:62257823-62257823;hs1:118202326-118202326,hs4:62214589-62214589;hs1:118202917-118202917,hs4:68130589-68130589;hs1:118212065-118212065,hs4:68085547-68085547;hs1:118213100-118213100,hs4:66461586-66461586;hs1:149848864-149848864,hs4:66461122-66461122;hs1:149849107-149849107,hs4:62675345-62675345;hs1:149849397-149849397,hs4:67785141-67785141;hs1:149851969-149851969,hs4:68096639-68096639;hs1:149857304-149857304,hs1:150114821-150114821;hs1:149857606-149857606,hs4:68115132-68115132;hs1:149859337-149859337,hs4:66417295-66417295;hs1:149859793-149859793,hs13:45014739-45014739;hs1:149860562-149860562,hs4:68130487-68130487;hs1:149861374-149861374,hs4:62341741-62341741;hs1:149866964-149866964,hs4:66343595-66343595;hs1:149990170-149990170,hs13:43252566-43252566;hs1:149995285-149995285,hs4:65401213-65401213;hs1:149995946-149995946,hs13:44492215-44492215;hs1:149996435-149996435,hs4:66465174-66465174;hs1:149997366-149997366,hs4:66461038-66461038;hs1:149998608-149998608,hs4:65660854-65660854;hs1:149999602-149999602,hs4:65646567-65646567;hs1:150001035-150001035,hs4:62215557-62215557;hs1:150001843-150001843,hs4:68108984-68108984;hs1:150002053-150002053,hs4:66446101-66446101;hs1:150005040-150005040,hs4:68079876-68079876;hs1:150005117-150005117,hs4:65374904-65374904;hs1:150007609-150007609,hs4:66348350-66348350;hs1:150007940-150007940,hs4:68107554-68107554;hs1:150008941-150008941,hs4:65355673-65355673;hs1:150014262-150014262,hs1:150082215-150082215;hs1:150015763-150015763,hs13:45013664-45013664;hs1:150016145-150016145,hs4:67791299-67791299;hs1:150023873-150023873,hs4:65665275-65665275;hs1:150034057-150034057,hs4:66474679-66474679;hs1:150036966-150036966,hs4:68058416-68058416;hs1:150041401-150041401,hs4:66348015-66348015;hs1:150046269-150046269,hs4:66420702-66420702;hs1:150047039-150047039,hs4:68111291-68111291;hs1:150049045-150049045,hs4:66461507-66461507;hs1:150049620-150049620,hs4:66362229-66362229;hs1:150049715-150049715,hs4:66469713-66469713;hs1:150053221-150053221,hs4:65353895-65353895;hs1:150055330-150055330,hs1:150078333-150078333;hs1:150056429-150056429,hs1:150070879-150070879;hs1:150057569-150057569,hs4:68037726-68037726;hs1:150058001-150058001,hs4:62048307-62048307;hs1:150058019-150058019,hs4:68105894-68105894;hs1:150059515-150059515,hs4:68114663-68114663;hs1:150063229-150063229,hs4:65645013-65645013;hs1:150063478-150063478,hs4:66377608-66377608;hs1:150064205-150064205,hs4:62008781-62008781;hs1:150065942-150065942,hsX:88440921-88440921;hs1:150068191-150068191,hs4:66452211-66452211;hs1:150070986-150070986,hs4:68110040-68110040;hs1:150079750-150079750,hs4:65653495-65653495;hs1:150081544-150081544,hs4:68075331-68075331;hs1:150082366-150082366,hs4:68130172-68130172;hs1:150082386-150082386,hs4:68083941-68083941;hs1:150101272-150101272,hs4:68034474-68034474;hs1:150105808-150105808,hs4:68106558-68106558;hs1:150107509-150107509,hs4:68104396-68104396;hs1:150108020-150108020,hs4:68105482-68105482;hs1:150109411-150109411,hs4:65405235-65405235;hs1:150110685-150110685,hs4:68111900-68111900;hs1:150116019-150116019,hs4:66390634-66390634;hs1:150116565-150116565,hs4:65654517-65654517;hs1:150116586-150116586,hs4:68128254-68128254;hs1:150117064-150117064,hs4:66471433-66471433;hs1:150121255-150121255,hs4:66474308-66474308;hs1:150123551-150123551,hs4:66420857-66420857;hs1:150124819-150124819,hs4:62449144-62449144;hs1:150124865-150124865,hs4:65379621-65379621;hs1:150125049-150125049,hs4:66467065-66467065;hs1:150125191-150125191,hs4:65359103-65359103;hs1:150129386-150129386,hs4:62856274-62856274;hs1:150131177-150131177,hs4:66363159-66363159;hs1:150131625-150131625,hs4:62047450-62047450;hs1:150131625-150131625,hs4:66456031-66456031;hs1:150131625-150131625,hs4:66474680-66474680;hs1:150131940-150131940,hs4:68129510-68129510;hs1:150132757-150132757,hs4:62850099-62850099;hs1:150132757-150132757,hs4:66406321-66406321;hs1:150132757-150132757,hs4:68106318-68106318;hs1:150134306-150134306,hs4:66387898-66387898;hs1:150135401-150135401,hs4:66377814-66377814;hs1:150135482-150135482,hs4:62917811-62917811;hs1:150136153-150136153,hs4:66378420-66378420;hs1:150136748-150136748,hs4:62317704-62317704;hs1:150138016-150138016,hsX:88427612-88427612;hs4:59635010-59635010,hs4:65402873-65402873;hs4:59645763-59645763,hs4:62017364-62017364;hs4:59649523-59649523,hs4:62844854-62844854;hs4:61921786-61921786,hs4:68102217-68102217;hs4:62000093-62000093,hs4:62449478-62449478;hs4:62004873-62004873,hs4:68075123-68075123;hs4:62005781-62005781,hsX:88399608-88399608;hs4:62007446-62007446,hs4:67730201-67730201;hs4:62007563-62007563,hs4:65656008-65656008;hs4:62020414-62020414,hs4:68095469-68095469;hs4:62020542-62020542,hs4:66477823-66477823;hs4:62027232-62027232,hs4:66377578-66377578;hs4:62041882-62041882,hs4:62749815-62749815;hs4:62047884-62047884,hs13:43292718-43292718;hs4:62084805-62084805,hs4:65370217-65370217;hs4:62088343-62088343,hs4:66471627-66471627;hs4:62089367-62089367,hs4:68066307-68066307;hs4:62092189-62092189,hs4:62328085-62328085;hs4:62092355-62092355,hs4:68112199-68112199;hs4:62095456-62095456,hs4:68110914-68110914;hs4:62232880-62232880,hs4:62824984-62824984;hs4:62271933-62271933,hs4:68054742-68054742;hs4:62307872-62307872,hs4:63051312-63051312;hs4:62323901-62323901,hs4:66480058-66480058;hs4:62328089-62328089,hs4:68112676-68112676;hs4:62338806-62338806,hs4:68116966-68116966;hs4:62367115-62367115,hs4:62719499-62719499;hs4:62407582-62407582,hs4:65406056-65406056;hs4:62424171-62424171,hs4:65357661-65357661;hs4:62449397-62449397,hs13:43277729-43277729;hs4:62449734-62449734,hs4:66388921-66388921;hs4:62449875-62449875,hs4:65658988-65658988;hs4:62450675-62450675,hs4:62833903-62833903;hs4:62462659-62462659,hsX:88399308-88399308;hs4:62588330-62588330,hs4:62832090-62832090;hs4:62592602-62592602,hs4:66480317-66480317;hs4:62602498-62602498,hs4:66365952-66365952;hs4:62615874-62615874,hs4:65360322-65360322;hs4:62619148-62619148,hs4:65352163-65352163;hs4:62643654-62643654,hs4:66380614-66380614;hs4:62645505-62645505,hs4:66377788-66377788;hs4:62681058-62681058,hs4:65369859-65369859;hs4:62691727-62691727,hs4:68028760-68028760;hs4:62694626-62694626,hs4:68100524-68100524;hs4:62695010-62695010,hs4:66482909-66482909;hs4:62703248-62703248,hs4:62963059-62963059;hs4:62708491-62708491,hs4:65341371-65341371;hs4:62709223-62709223,hs4:68075645-68075645;hs4:62710767-62710767,hs4:68073153-68073153;hs4:62711623-62711623,hs4:68057589-68057589;hs4:62712089-62712089,hs13:43279613-43279613;hs4:62749406-62749406,hsX:88388054-88388054;hs4:62830574-62830574,hs4:62928718-62928718;hs4:62835529-62835529,hs4:68111182-68111182;hs4:62840515-62840515,hs4:65646377-65646377;hs4:62840723-62840723,hsX:88399040-88399040;hs4:62844580-62844580,hs4:66378159-66378159;hs4:62845423-62845423,hs4:66446296-66446296;hs4:62847290-62847290,hs4:68101038-68101038;hs4:62847955-62847955,hsX:88408052-88408052;hs4:62849769-62849769,hs4:66406322-66406322;hs4:62918024-62918024,hs4:66378252-66378252;hs4:62918878-62918878,hs4:66482340-66482340;hs4:62919379-62919379,hs4:67938161-67938161;hs4:62921643-62921643,hs4:66365885-66365885;hs4:62925158-62925158,hs4:66382189-66382189;hs4:65354185-65354185,hs4:66383940-66383940;hs4:65359219-65359219,hs4:68109906-68109906;hs4:65360289-65360289,hs4:68100880-68100880;hs4:65360437-65360437,hs4:68123007-68123007;hs4:65360574-65360574,hs4:68051015-68051015;hs4:65360959-65360959,hs4:66377624-66377624;hs4:65362355-65362355,hs4:68101776-68101776;hs4:65367893-65367893,hs4:68105242-68105242;hs4:65369048-65369048,hs4:68058234-68058234;hs4:65387380-65387380,hs4:66455253-66455253;hs4:65402528-65402528,hs4:66477557-66477557;hs4:65407272-65407272,hs4:68113892-68113892;hs4:65413969-65413969,hs4:68084041-68084041;hs4:65645164-65645164,hs4:65654765-65654765;hs4:65654698-65654698,hs4:68123407-68123407;hs4:65655489-65655489,hs4:68104368-68104368;hs4:65655633-65655633,hs4:68051732-68051732;hs4:65656962-65656962,hs4:68126300-68126300;hs4:65661082-65661082,hs13:44650469-44650469;hs4:65665279-65665279,hs4:68036766-68036766;hs4:66365182-66365182,hs4:66482259-66482259;hs4:66365771-66365771,hs4:68099905-68099905;hs4:66366747-66366747,hs4:68104031-68104031;hs4:66374332-66374332,hs4:66405140-66405140;hs4:66376576-66376576,hs4:68102016-68102016;hs4:66377779-66377779,hs4:68088510-68088510;hs4:66378214-66378214,hs4:66455597-66455597;hs4:66388330-66388330,hs4:66447606-66447606;hs4:66388569-66388569,hs13:43303915-43303915;hs4:66392931-66392931,hs4:68106581-68106581;hs4:66402479-66402479,hs4:66475328-66475328;hs4:66418526-66418526,hs4:66481953-66481953;hs4:66420228-66420228,hs4:68104024-68104024;hs4:66445191-66445191,hs4:68104409-68104409;hs4:66445278-66445278,hs4:68116192-68116192;hs4:66446101-66446101,hs4:68056223-68056223;hs4:66446433-66446433,hs13:43287404-43287404;hs4:66446518-66446518,hs4:66457333-66457333;hs4:66448027-66448027,hs4:68106930-68106930;hs4:66459389-66459389,hs4:68098350-68098350;hs4:66460508-66460508,hs4:68125570-68125570;hs4:66460815-66460815,hs13:44651315-44651315;hs4:66470902-66470902,hs4:66482176-66482176;hs4:66476409-66476409,hs4:68109549-68109549;hs4:66479702-66479702,hs4:68103327-68103327;hs4:66480317-66480317,hs4:68087144-68087144;hs4:66482195-66482195,hs4:66483306-66483306;hs4:66482802-66482802,hsX:88423770-88423770;hs4:67727876-67727876,hs4:68117623-68117623;hs4:67729537-67729537,hs4:68008883-68008883;hs4:67785140-67785140,hs4:68109232-68109232;hs4:67947105-67947105,hs13:43277107-43277107;hs4:67951282-67951282,hs4:68106179-68106179;hs4:68037663-68037663,hs4:68111794-68111794;hs4:68037730-68037730,hs4:68105986-68105986;hs4:68055595-68055595,hsX:88425146-88425146;hs4:68058000-68058000,hs13:45016040-45016040;hs4:68086369-68086369,hs4:68095468-68095468;hs4:68098342-68098342,hs4:68172167-68172167;hs4:68104682-68104682,hs4:68109948-68109948;hs4:68105168-68105168,hsX:88398471-88398471;hs4:68105492-68105492,hs4:68127082-68127082;hs4:68109344-68109344,hsX:88411190-88411190;hs4:68122167-68122167,hs4:68125532-68125532;hs4:68122311-68122311,hsX:88402550-88402550;hs4:68123146-68123146,hs13:44653493-44653493;hs4:68128298-68128298,hs4:68131123-68131123;hs4:68130724-68130724,hs13:44866366-44866366;hs4:190201030-190201030,hs20:29653850-29653850;hs13:43202549-43202549,hs13:43839940-43839940;hs13:43202702-43202702,hs13:44649619-44649619;hs13:43203670-43203670,hs13:43212981-43212981;hs13:43209242-43209242,hs13:45014132-45014132;hs13:43210624-43210624,hs13:44666090-44666090;hs13:43211383-43211383,hs13:45481661-45481661;hs13:43212096-43212096,hs13:44866618-44866618;hs13:43280093-43280093,hs13:44294543-44294543;hs13:43280265-43280265,hs13:45526974-45526974;hs13:43281392-43281392,hs13:44295507-44295507;hs13:43303690-43303690,hs13:43316250-43316250;hs13:43304962-43304962,hs13:44663222-44663222;hs13:43305504-43305504,hs13:44490453-44490453;hs13:43307839-43307839,hs13:44668222-44668222;hs13:43310426-43310426,hs13:44281474-44281474;hs13:43313893-43313893,hs13:44892677-44892677;hs13:43815700-43815700,hs13:44892535-44892535;hs13:43839941-43839941,hs13:44649621-44649621;hs13:44294279-44294279,hs13:44890836-44890836;hs13:44492217-44492217,hs13:44877324-44877324;hs13:44666462-44666462,hs13:44894360-44894360;hs13:44666846-44666846,hs13:44670225-44670225 ADC;CAPZB;CSF3R;CSMD2;DDAH1;DENND2C;ECE1;EIF4G3;ENOX1;EPHA5;EPHB2;FHAD1;FHL3;FLJ32224;HFM1;HIST2H2AB;HIST2H2AC;HIST2H2BE;LAPTM5;LPHN3;MAGI3;NUFIP1;PLEKHO1;ST6GALNAC3;TMEM50A;TSC22D1;VPS45;ZBTB40;ZSWIM5; Oncogenomics Section, Pediatric Oncology Branch, Advanced Technology Center, National Cancer Institute, Bethesda, Maryland, United States of America Neuroblastoma is one of the most genomically heterogeneous childhood malignances studied to date, and the molecular events that occur during the course of the disease are not fully understood. Genomic studies in neuroblastoma have showed only a few recurrent mutations and a low somatic mutation burden. However, none of these studies has examined the mutations arising during the course of disease, nor have they systemically examined the expression of mutant genes. Here we performed genomic analyses on tumors taken during a 3.5 years disease course from a neuroblastoma patient (bone marrow biopsy at diagnosis, adrenal primary tumor taken at surgical resection, and a liver metastasis at autopsy). Whole genome sequencing of the index liver metastasis identified 44 non-synonymous somatic mutations in 42 genes (0.85 mutation/MB) and a large hemizygous deletion in the ATRX gene which has been recently reported in neuroblastoma. Of these 45 somatic alterations, 15 were also detected in the primary tumor and bone marrow biopsy, while the other 30 were unique to the index tumor, indicating accumulation of de novo mutations during therapy. Furthermore, transcriptome sequencing on the 3 tumors demonstrated only 3 out of the 15 commonly mutated genes (LPAR1, GATA2, and NUFIP1) had high level of expression of the mutant alleles, suggesting potential oncogenic driver roles of these mutated genes. Among them, the druggable G-protein coupled receptor LPAR1 was highly expressed in all tumors. Cells expressing the LPAR1 R163W mutant demonstrated a significantly increased motility through elevated Rho signaling, but had no effect on growth. Therefore, this study highlights the need for multiple biopsies and sequencing during progression of a cancer and combinatorial DNA and RNA sequencing approach for systematic identification of expressed driver mutations. GRCh37/hg19 Yes CAPZB,ZSWIM5;CDC45,SEPT5;CSMD2,ST6GALNAC3;DENND2C,EPHA5;DENND2C,LPHN3;ECE1,LAPTM5;EIF4G3,CSF3R;EPHB2,ADC;FHAD1,FHL3;HIST2H2AB,EPHA5;HIST2H2AB,TSC22D1;HIST2H2AC,TSC22D1;HIST2H2BE,VPS45;LPHN3,EPHA5;MAGI3,DENND2C;MAGI3,EPHA5;MAGI3,LPHN3;MAGI3,PLEKHO1;MAGI3,VPS45;PLEKHO1,EPHA5;PLEKHO1,LPHN3;RSPH6A,SYMPK;SEPT5,GP1BB;VPS45,EPHA5;ZBTB40,EPHB2;ZNF26,ZNF84 CTDB0358 Research 22362584 Natrajan R, Mackay A, Lambros MB, Weigelt B, Wilkerson PM, Manie E, Grigoriadis A, A'hern R, van der Groep P, Kozarewa I, Popova T, Mariani O, Turajlic S, Furney SJ, Marais R, Rodruigues DN, Flora AC, Wai P, Pawar V, McDade S, Carroll J, Stoppa-Lyonnet D, Green AR, Ellis IO, Swanton C, van Diest P, Delattre O, Lord CJ, Foulkes WD, Vincent-Salomon A, Ashworth A, Henri Stern M, Reis-Filho JS A whole-genome massively parallel sequencing analysis of BRCA1 mutant oestrogen receptor-negative and -positive breast cancers The Journal of Pathology 2012 May 6,X Breast cancer Next Generation Sequencing Homo sapiens BRCA1/ER+BC Complete Genomics The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, UK BRCA1 encodes a tumour suppressor protein that plays pivotal roles in homologous recombination (HR) DNA repair, cell-cycle checkpoints, and transcriptional regulation. BRCA1 germline mutations confer a high risk of early-onset breast and ovarian cancer. In more than 80% of cases, tumours arising in BRCA1 germline mutation carriers are oestrogen receptor (ER)-negative; however, up to 15% are ER-positive. It has been suggested that BRCA1 ER-positive breast cancers constitute sporadic cancers arising in the context of a BRCA1 germline mutation rather than being causally related to BRCA1 loss-of-function. Whole-genome massively parallel sequencing of ER-positive and ER-negative BRCA1 breast cancers, and their respective germline DNAs, was used to characterize the genetic landscape of BRCA1 cancers at base-pair resolution. Only BRCA1 germline mutations, somatic loss of the wild-type allele, and TP53 somatic mutations were recurrently found in the index cases. BRCA1 breast cancers displayed a mutational signature consistent with that caused by lack of HR DNA repair in both ER-positive and ER-negative cases. Sequencing analysis of independent cohorts of hereditary BRCA1 and sporadic non-BRCA1 breast cancers for the presence of recurrent pathogenic mutations and/or homozygous deletions found in the index cases revealed that DAPK3, TMEM135, KIAA1797, PDE4D, and GATA4 are potential additional drivers of breast cancers. This study demonstrates that BRCA1 pathogenic germline mutations coupled with somatic loss of the wild-type allele are not sufficient for hereditary breast cancers to display an ER-negative phenotype, and has led to the identification of three potential novel breast cancer genes (ie DAPK3, TMEM135, and GATA4). GRCh37/hg19 Yes SUPT6H,ARHGAP12;EXT2,TTC17 CTDB0359 Research 22237106 Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG The genetic basis of early T-cell precursor acute lymphoblastic leukaemia Nature 2012 Jan 1,11,12 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens STJALL001 chr10:0-135374737:0;chr11:0-61155471:0;chr11:134436401-134452384:0;chr11:61155472-70912249:-1;chr11:70912250-77979119:0;chr11:77979120-79868685:-1;chr11:79868686-80914909:0;chr11:80914910-81015904:1;chr11:81015905-82756272:0;chr11:82756273-83023070:1;chr11:83023071-83642443:0;chr11:83642444-134436400:-1;chr12:0-0:0;chr12:1-4034408:1;chr12:11787382-11852551:-1;chr12:11852551-21227923:-1;chr12:21227923-22066294:1;chr12:22066294-26671330:-1;chr12:26671330-28194413:1;chr12:28194414-132349534:0;chr12:4034408-11787382:-1;chr13:0-36416293:0;chr13:114028001-114142980:0;chr13:36416294-114028000:-1;chr14:0-106368585:0;chr15:0-100338915:0;chr16:0-88827254:0;chr17:0-78774742:0;chr18:0-75851817:0;chr18:75851818-76106200:-1;chr18:76106201-76117153:0;chr19:0-63811651:0;chr1:0-635200:0;chr1:183681561-184318407:1;chr1:184318408-185391929:0;chr1:185391930-222493387:1;chr1:222493388-226744537:0;chr1:226744538-232978811:1;chr1:232978812-233022500:0;chr1:233022501-247149600:1;chr1:247149601-247249719:0;chr1:635201-8847300:-1;chr1:8847301-183681560:0;chr20:0-62435964:0;chr21:0-46944323:0;chr22:0-49691432:0;chr2:0-242951149:0;chr3:0-199501827:0;chr4:0-191273063:0;chr5:0-180857866:0;chr6:0-94419549:0;chr6:94419550-95073427:-1;chr6:95073428-170899992:0;chr7:0-99532387:0;chr7:142194036-142205270:0;chr7:142205271-158821462:1;chr7:158821463-158821424:0;chr7:99532388-142194035:1;chr8:0-180567:0;chr8:180568-25681600:1;chr8:25681601-25681600:0;chr8:25681601-89256109:1;chr8:89256110-146274826:0;chr9:0-80097141:0;chr9:103678699-140273252:0;chr9:80097142-103678698:-1;chrX:0-0:0;chrX:1-40412672:1;chrX:40412673-154913754:0;chrY:0-57772954:0 hs1:185391933-185391933,hs1:183681561-183681561;hs1:211055963-211055963,hs1:226744535-226744535;hs1:211056775-211056775,hs1:185394336-185394336;hs1:222493387-222493387,hs1:211057022-211057022;hs4:6947258-6947258,hs4:6960707-6960707;hs4:53945291-53945291,hs7:27172066-27172066;hs4:53945348-53945348,hs8:89256006-89256006;hs6:95073427-95073427,hs11:80914910-80914910;hs7:27171985-27171985,hsX:40412627-40412627;hs10:21278245-21278245,hs10:21279404-21279404;hs11:81015904-81015904,hs6:94419550-94419550;hs11:43874661-43874661,hs11:77957935-77957935;hs11:61155472-61155472,hs11:70912250-70912250;hs11:77979120-77979120,hs11:82756273-82756273;hs11:79868681-79868681,hs11:43875121-43875121;hs11:79873315-79873315,hs11:83007059-83007059;hs11:83023070-83023070,hs12:28194412-28194412;hs12:4034408-4034408,hs12:21227923-21227923;hs12:11787386-11787386,hs12:11852551-11852551;hs12:22066294-22066294,hs12:26671330-26671330;hs14:21977845-21977845,hs14:21988920-21988920;hsX:40412669-40412669,hs8:89256109-89256109 A2M;A2ML1;AASDHPPT;ABCB10;ABCC9;ABCG4;ACAD8;ACAP3;ACAT1;ACOT7;ACRBP;ACRV1;ACSM4;ACTA1;ACTN2;ACTN3;ACTRT2;ACY3;ADAMTS15;ADAMTS8;ADIPOR1;ADIPOR2;ADORA1;ADRBK1;ADSS;AEBP2;AGRN;AGT;AHCTF1;AHNAK;AICDA;AIDA;AIP;AJAP1;AKAP3;ALDH3B1;ALDH3B2;ALG9;ALKBH3;ALKBH8;AMICA1;AMOTL1;ANGEL2;ANGPTL5;ANKK1;ANKRD13D;ANKRD49;ANO1;ANO2;APLP2;APOA1;APOA4;APOA5;APOBEC1;APOC3;APOLD1;ARCN1;ARHGDIB;ARHGEF16;ARID4B;ARL2;ARL8A;ARNTL2;ART4;ARV1;ASPM;ASRGL1;ATAD3A;ATAD3B;ATAD3C;ATF3;ATF7IP;ATG2A;ATL3;ATN1;ATP2B4;ATPGD1;AURKAIP1;AURKAPS1;AVPR1B;B3GALNT2;B3GALT2;B3GALT6;B3GAT3;B4GALNT3;BAD;BANF1;BATF2;BATF3;BBS1;BCAT1;BCL2L14;BHLHE41;BPNT1;BTG2;C12orf11;C12orf32;C12orf36;C12orf39;C12orf4;C12orf5;C12orf53;C12orf57;C12orf59;C12orf60;C12orf67;C12orf69;C12orf70;C12orf71;C12orf77;C1orf100;C1orf101;C1orf106;C1orf107;C1orf115;C1orf116;C1orf124;C1orf131;C1orf150;C1orf159;C1orf170;C1orf174;C1orf198;C1orf229;C1orf31;C1orf57;C1orf70;C1orf86;C1orf96;C1R;C1RL;C1S;C3AR1;C7orf34;C8orf48;C8orf58;C9orf129;C9orf153;C9orf156;C9orf170;CACNA1C;CACNA2D4;CALML6;CAMTA1;CAPN9;CAPZA3;CASC1;CCDC27;CCDC77;CCND2;CD163L1;CDKN1B;CEP170;CHML;CHRM3;CMAS;CNST;COG2;CREBL2;DAD1L;DCP1B;DDX47;DERA;DISC1;DISC2;DLG2;DUSP16;DUSP5P;EDARADD;EFCAB2;EFCAB4B;EGLN1;EMP1;EPS8;ERC1;ERO1LB;ERP27;ETNK1;ETV6;EXO1;EXOC8;FAM138D;FAM36A;FAM89A;FBXL14;FGFR1OP2;FH;FKBP4;FOXM1;GALNT2;GNPAT;GOLT1B;GPR19;GYS2;HMCN1;HSN2;IAPP;IFLTD1;IQSEC3;ITFG2;ITPR2;KCNJ8;KDM5A;KIAA0528;KLHDC5;KRAS;LDHB;LOC100130522;LOC100133893;LOC100292680;LRMP;LRTM2;LYRM5;MED21;MIR920;MRPS35;NINJ2;NVL;ODZ4;PPFIBP1;PTHLH;PYROXD1;RASSF8;RECQL;REP15;RNF187;RPLP0P2;SLCO1A2;SLCO1B1;SOX5;SSPN;ST8SIA1;STK38L;TATDN3;TM7SF3; Department of Computational Biology and Bioinformatics, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL. NCBI 36/hg18 phs000340 Yes NA CTDB0360 Research 22237106 Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG The genetic basis of early T-cell precursor acute lymphoblastic leukaemia Nature 2012 Jan 2,9 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens STJALL002 chr10:0-135374737:0;chr11:0-134452384:0;chr12:0-8545706:0;chr12:27480227-132349534:0;chr12:8545707-27480226:-1;chr13:0-114142980:0;chr14:0-106368585:0;chr15:0-100338915:0;chr16:0-75555812:0;chr16:75555813-75582197:1;chr16:75582198-88827254:0;chr17:0-78774742:0;chr18:0-76117153:0;chr19:0-0:0;chr19:1-63793700:1;chr19:63793701-63811651:0;chr1:0-91721921:0;chr1:100818677-103024856:-1;chr1:103024857-247249719:0;chr1:91721922-93409158:-1;chr1:93409159-93589481:0;chr1:93589482-97369434:-1;chr1:97369435-97385719:0;chr1:97385720-97385843:-1;chr1:97385844-100818676:0;chr20:0-62435964:0;chr21:0-46944323:0;chr22:0-0:0;chr22:1-49491400:1;chr22:49491401-49691432:0;chr2:0-206579746:0;chr2:206579747-207028592:1;chr2:207028592-207725565:1;chr2:207725565-209229004:1;chr2:209229004-210601250:1;chr2:210601250-210911367:1;chr2:210911367-211035238:1;chr2:211035238-213106802:1;chr2:213106802-213129128:1;chr2:213129128-242651100:-1;chr2:242651101-242951149:0;chr3:0-199501827:0;chr4:0-191273063:0;chr5:0-180857866:0;chr6:0-30822391:0;chr6:30822392-32895237:-1;chr6:32895238-170899992:0;chr7:0-50144815:0;chr7:50144816-50421851:-1;chr7:50421852-158821424:0;chr8:0-115945867:0;chr8:115945868-116017817:1;chr8:116017818-146274826:0;chr9:0-29999:0;chr9:104248373-105070517:-1;chr9:105070518-118874264:0;chr9:118874265-120461292:-1;chr9:120461293-140273252:0;chr9:21096626-22880450:-1;chr9:22880450-70510800:-1;chr9:30000-21096626:-1;chr9:70510800-70705182:-1;chr9:70705182-72993063:-1;chr9:72993063-73941820:-1;chr9:73941820-76718037:-1;chr9:76718037-77929470:-1;chr9:77929470-78271717:-1;chr9:78271718-78705695:0;chr9:78705696-83900722:-1;chr9:83900723-87880619:0;chr9:87880620-89388052:-1;chr9:89388053-104248372:0;chrX:0-68505335:0;chrX:68505336-69493999:1;chrX:69493999-69701501:1;chrX:69701501-70174245:1;chrX:70174245-70800355:1;chrX:70800356-154913754:0;chrY:0-57772954:0 hs1:91721922-91721922,hs1:97385720-97385720;hs1:93589482-93589482,hs1:100818677-100818677;hs1:97385843-97385843,hs1:97369434-97369434;hs1:103024856-103024856,hs1:93409158-93409158;hs2:213106802-213106802,hs2:207028592-207028592;hs2:213129128-213129128,hs2:207725565-207725565;hs2:209229004-209229004,hsX:68505336-68505336;hs7:50144816-50144816,hs7:50421851-50421851;hs8:116017817-116017817,hs8:115945868-115945868;hs9:21096626-21096626,hs9:118874265-118874265;hs9:72993063-72993063,hs9:78271717-78271717;hs9:76718037-76718037,hs9:105070517-105070517;hs9:83900722-83900722,hs9:70705182-70705182;hs9:87880620-87880620,hs9:89388052-89388052;hs9:104248373-104248373,hs9:120461292-120461292;hs9:126600441-126600441,hs9:126599797-126599797;hs12:11921859-11921859,hs2:206579740-206579740;hs12:91128883-91128883,hs12:27480226-27480226;hs16:75582197-75582197,hs16:75555813-75555813;hsX:69493999-69493999,hs2:210601250-210601250;hsX:70174245-70174245,hs2:211035238-211035238;hsX:70800355-70800355,hs2:206579747-206579747;hsX:70800356-70800356,hs12:11922106-11922106;hsX:69550634-69550634,hsX:69551230-69551230 AAMP;ABCA12;ABCB6;ACADL;ACCN4;ACER2;ACO1;ACSL3;ADAM23;ADAMTSL1;AGAP1;AGFG1;AGXT;AK3;ALDH1A1;ALDH1B1;ALPI;ALPP;ALPPL2;ANKMY1;ANKRD20A1;ANKRD20A2;ANKRD20A3;ANKRD20A4;ANKZF1;ANO7;ANXA1;ANXA2P2;AP1S3;APTX;AQP12A;AQP12B;AQP3;AQP7;AQP7P1;AQP7P2;AQP7P3;ARID3C;ARL4C;ARMC9;ARPC2;ASTN2;B4GALT1;BAG1;BG201338;BNC2;C12orf60;C2orf67;C2orf80;C6orf10;C6orf15;C6orf25;C9orf100;C9orf11;C9orf122;C9orf123;C9orf128;C9orf135;C9orf150;C9orf153;C9orf170;C9orf40;C9orf41;C9orf46;C9orf53;C9orf57;C9orf66;C9orf68;C9orf70;C9orf85;C9orf93;C9orf95;CBWD1;CCNYL1;CD274;CDC37L1;CDKN2A;CDKN2B;CDKN2BAS;CEP78;CER1;CNTLN;CPO;CREB1;CRYGA;CRYGB;CRYGC;CRYGD;CYLC2;DAPK1;DENND4C;DMRT1;DMRT2;DMRT3;DMRTA1;DYTN;EEF1B2;ERBB4;FAM108B1;FAM119A;FAM122A;FAM189A2;FASTKD2;FLJ43859;FLJ43950;FLJ44082;FLJ46321;FOXB2;FXN;FZD5;GAS1;GCNT1;GDA;GNA14;GNAQ;GOLM1;GPR1;IDH1;IFNA1;IFNA10;IFNA13;IFNA14;IFNA16;IFNA17;IFNA2;IFNA21;IFNA4;IFNA5;IFNA6;IFNA7;IFNA8;IFNE;IFNW1;INO80D;ISCA1;KLF7;KLF9;LANCL1;LOC100130426;LOC29034;MAP2;MDH1B;MIR204;MIR548F2;MYL1;NDUFS1;OSTF1;PCSK5;PIKFYVE;PIP5K1B;PLEKHM3;PRKACG;PRUNE2;PSAT1;PTAR1;PTH2R;RFK;RORB;RPE;RPSAP9;SMC5;SNORA70C;SNORD51;TJP2;TLE1;TLE4;TLR4;TMC1;TMEM2;TRPM3;TRPM6;UNC80;VPS13A;ZCCHC6;ZDBF2;ZFAND5; Department of Computational Biology and Bioinformatics, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL. NCBI 36/hg18 phs000340 Yes C2orf67,KIF4A;ETV6,INO80D;INO80D,BG201338 CTDB0361 Research 22237106 Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG The genetic basis of early T-cell precursor acute lymphoblastic leukaemia Nature 2012 Jan 1,4,5,9,10 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens STJALL003 chr10:0-7430589:0;chr10:24920178-63614386:0;chr10:63614387-66275073:-1;chr10:66275074-68176655:0;chr10:68176656-68950041:-1;chr10:68950042-76649371:0;chr10:7430590-24920177:-1;chr10:76649372-78529151:-1;chr10:78529152-80761759:0;chr10:80761760-96821276:-1;chr10:96821277-135374737:0;chr11:0-134452384:0;chr12:0-132349534:0;chr13:0-114142980:0;chr14:0-97862275:0;chr14:97862276-98116066:-1;chr14:98116067-106368585:0;chr15:0-100338915:0;chr16:0-84850282:0;chr16:84850283-85033002:-1;chr16:85033003-88827254:0;chr17:0-78774742:0;chr18:0-60008337:0;chr18:60008338-60413979:-1;chr18:60413980-61115803:0;chr18:61115804-61276902:-1;chr18:61276903-76117153:0;chr19:0-63811651:0;chr1:0-65943700:0;chr1:106673274-107678605:-1;chr1:107678606-107716341:0;chr1:107716342-144004701:-1;chr1:144004702-247249719:0;chr1:65943701-77157200:-1;chr1:77157201-78144610:0;chr1:78144611-78755005:-1;chr1:78755006-106673273:0;chr20:0-62435964:0;chr21:0-46944323:0;chr22:0-49691432:0;chr2:0-242951149:0;chr3:0-199501827:0;chr4:0-84837682:0;chr4:125893225-135358957:-1;chr4:135358958-191273063:0;chr4:84837683-96243984:-1;chr4:96243985-125893224:0;chr5:0-6776459:0;chr5:116236493-116328132:1;chr5:116328133-117950913:0;chr5:117950914-122015240:-1;chr5:122015241-180857866:0;chr5:13467228-61592429:0;chr5:61592430-67173064:-1;chr5:67173065-116236492:0;chr5:6776460-7052197:-1;chr5:7052198-7070447:0;chr5:7070448-13467227:-1;chr6:0-170899992:0;chr7:0-158821424:0;chr8:0-146274826:0;chr9:0-15805305:0;chr9:15805306-15811941:1;chr9:15811942-20310301:0;chr9:20310302-21615196:-1;chr9:21615196-21778860:-1;chr9:21778860-22282780:-1;chr9:22282780-31089571:-1;chr9:31089571-31827466:-1;chr9:31827467-38084084:0;chr9:38084085-38301919:-1;chr9:38301920-38906324:0;chr9:38906325-38993888:-1;chr9:38993889-140273252:0;chrX:0-154913754:0;chrY:0-57772954:0 hs1:78144611-78144611,hs1:65935999-65935999;hs1:107716342-107716342,hs1:77157121-77157121;hs1:163486878-163486878,hs1:163486903-163486903;hs1:65943763-65943763,hs10:24920177-24920177;hs1:107678605-107678605,hs10:66275073-66275073;hs4:84837683-84837683,hs4:135358957-135358957;hs4:159764088-159764088,hs10:7430590-7430590;hs4:159770296-159770296,hs10:24923739-24923739;hs5:67173064-67173064,hs4:135348611-135348611;hs5:6776460-6776460,hs5:7070448-7070448;hs5:117950914-117950914,hs5:116328132-116328132;hs5:7052197-7052197,hs10:66301865-66301865;hs5:61592430-61592430,hs10:96821276-96821276;hs9:21778860-21778860,hs9:38301919-38301919;hs9:38084085-38084085,hs9:22282780-22282780;hs9:38993888-38993888,hs9:21615196-21615196;hs10:66275072-66275072,hs1:107678605-107678605;hs10:80761760-80761760,hs1:78755007-78755007;hs10:63614387-63614387,hs4:96243984-96243984;hs10:66301858-66301858,hs4:125893225-125893225;hs10:24923743-24923743,hs10:68950041-68950041;hs10:76649372-76649372,hs10:78529151-78529151;hs16:84850283-84850283,hs14:98116066-98116066;hs16:66071321-66071321,hs16:66071625-66071625;hs18:60008338-60008338,hs18:61276902-61276902 ABCG2;ACADM;ACBD7;ACTA2;ADAM30;ADAMTS6;ADCY2;ADO;ADORA3;AFF1;AGAP11;AHCYL1;AKNAD1;ALX3;AMIGO1;AMPD1;AMPD2;ANKRD1;ANKRD13C;ANKRD22;ANKRD33B;ANXA11;ANXA2P3;AP4B1;ARHGAP21;ARHGAP24;ARL5B;ARMC3;ASB17;ATAD1;ATOH1;ATP1A1;ATP5C1;ATP5F1;ATXN7L2;BCAS2;BCL2L15;BEND7;BMI1;BMPR1A;BMPR1B;BTAF1;C10orf11;C10orf111;C10orf113;C10orf114;C10orf116;C10orf140;C10orf4;C10orf41;C10orf47;C10orf57;C10orf58;C10orf67;C10orf99;C1orf103;C1orf141;C1orf152;C1orf161;C1orf162;C1orf173;C1orf183;C1QL3;C4orf12;C4orf29;C4orf33;C4orf36;C5orf44;C5orf49;C9orf11;C9orf53;C9orf72;C9orf82;CACNB2;CAMK1D;CCDC3;CCT5;CD180;CDC123;CDKN2A;CDKN2B;CDKN2B-AS1;CDNF;CDS1;CENPK;CEP55;CFLP1;CH25H;CMBL;COMMD3;COMTD1;CPEB3;CRYZ;CTH;CTNNA3;CTNND2;CYP26A1;CYP26C1;CYP2C18;DAP;DEPDC1;DIMT1L;DIRAS3;DMP1;DMRTA1;DMXL1;DNAJB4;DSPP;DTWD2;EGR2;ELAVL2;ERBB2IP;FAM13A;FAM13AOS;FAM159B;FAM170A;FAM173B;FAM190A;FASTKD3;FAT4;FPGT;FTMT;FUBP1;GADD45A;GIPC2;GNG12;GPR177;GPRIN3;GRID2;HERC3;HERC5;HERC6;HHLA3;HPGDS;HSD17B11;HSD17B4;HSPA4L;HTR1A;IFNA1;IFNA10;IFNA13;IFNA14;IFNA16;IFNA17;IFNA2;IFNA21;IFNA4;IFNA5;IFNA6;IFNA7;IFNA8;IFNB1;IFNE;IFNK;IFNW1;IFT74;IL12RB2;IL23R;INSL5;INTU;IPO11;ISCA1L;JMJD1C;KCNMA1;KIAA1797;KIF2A;KLHL9;LARP1B;LHX8;LINGO2;LOC554202;LOC732275;LOC84989;LOX;LRRC19;LRRC40;LRRC7;LRRC70;LRRTM3;MARCH6;MAST4;MFSD8;MGC27382;MIR1296;MIR31;MIR873;MIR876;MOBKL2B;MTAP;MTRR;NCRNA00032;NEXN;NLN;NRBF2;NTNG1;PABPC4L;PCDH10;PGRMC2;PHF17;PLAA;PLK4;POLS;PPWD1;PRMT6;PRR16;PTGFR;REEP3;RGS7BP;RNF180;ROPN1L;RTKN2;RXFP1;SCLT1;SDCCAG10;SEMA5A;SFMBT2;SFRS12IP1;SLC25A31;SNCAIP;SNORD123;SRFBP1;ST6GALNAC5;TAS2R1;TEK;TNFAIP8;TUSC1;VDAC2;ZNF365;ZNF474;ZNF503; Department of Computational Biology and Bioinformatics, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL. NCBI 36/hg18 phs000340 Yes ARHGAP21,RXFP1;CTNNA3,ARHGAP21;NTNG1,ST6GALNAC5;RXFP1,SFMBT2 CTDB0362 Research 22832583 Jones DT, Jager N, Kool M, Zichner T, Hutter B, Sultan M, Cho YJ, Pugh TJ, Hovestadt V, Stutz AM, Rausch T, Warnatz HJ, Ryzhova M, Bender S, Sturm D, Pleier S, Cin H, Pfaff E, Sieber L, Wittmann A, Remke M, Witt H, Hutter S, Tzaridis T, Weischenfeldt J, Raeder B, Avci M, Amstislavskiy V, Zapatka M, Weber UD, Wang Q, Lasitschka B, Bartholomae CC, Schmidt M, von Kalle C, Ast V, Lawerenz C, Eils J, Kabbe R, Benes V, van Sluis P, Koster J, Volckmann R, Shih D, Betts MJ, Russell RB, Coco S, Tonini GP, Schuller U, Hans V, Graf N, Kim YJ, Monoranu C, Roggendorf W, Unterberg A, Herold-Mende C, Milde T, Kulozik AE, von Deimling A, Witt O, Maass E, Rossler J, Ebinger M, Schuhmann MU, Fruhwald MC, Hasselblatt M, Jabado N, Rutkowski S, von Bueren AO, Williamson D, Clifford SC, McCabe MG, Collins VP, Wolf S, Wiemann S, Lehrach H, Brors B, Scheurlen W, Felsberg J, Reifenberger G, Northcott PA, Taylor MD, Meyerson M, Pomeroy SL, Yaspo ML, Korbel JO, Korshunov A, Eils R, Pfister SM, Lichter P Dissecting the genomic complexity underlying medulloblastoma Nature 2012 Aug 10 Medulloblastoma Next Generation Sequencing Homo sapiens ICGC_MB23 Illumina Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients. GRCh37/hg19 Yes NA CTDB0363 Research 22832583 Jones DT, Jager N, Kool M, Zichner T, Hutter B, Sultan M, Cho YJ, Pugh TJ, Hovestadt V, Stutz AM, Rausch T, Warnatz HJ, Ryzhova M, Bender S, Sturm D, Pleier S, Cin H, Pfaff E, Sieber L, Wittmann A, Remke M, Witt H, Hutter S, Tzaridis T, Weischenfeldt J, Raeder B, Avci M, Amstislavskiy V, Zapatka M, Weber UD, Wang Q, Lasitschka B, Bartholomae CC, Schmidt M, von Kalle C, Ast V, Lawerenz C, Eils J, Kabbe R, Benes V, van Sluis P, Koster J, Volckmann R, Shih D, Betts MJ, Russell RB, Coco S, Tonini GP, Schuller U, Hans V, Graf N, Kim YJ, Monoranu C, Roggendorf W, Unterberg A, Herold-Mende C, Milde T, Kulozik AE, von Deimling A, Witt O, Maass E, Rossler J, Ebinger M, Schuhmann MU, Fruhwald MC, Hasselblatt M, Jabado N, Rutkowski S, von Bueren AO, Williamson D, Clifford SC, McCabe MG, Collins VP, Wolf S, Wiemann S, Lehrach H, Brors B, Scheurlen W, Felsberg J, Reifenberger G, Northcott PA, Taylor MD, Meyerson M, Pomeroy SL, Yaspo ML, Korbel JO, Korshunov A, Eils R, Pfister SM, Lichter P Dissecting the genomic complexity underlying medulloblastoma Nature 2012 Aug 2 Medulloblastoma Next Generation Sequencing Homo sapiens MBRep_T53 Illumina MYCN;GLI2 Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients. GRCh37/hg19 Yes NA CTDB0364 Research 21892161 Bass AJ, Lawrence MS, Brace LE, Ramos AH, Drier Y, Cibulskis K, Sougnez C, Voet D, Saksena G, Sivachenko A, Jing R, Parkin M, Pugh T, Verhaak RG, Stransky N, Boutin AT, Barretina J, Solit DB, Vakiani E, Shao W, Mishina Y, Warmuth M, Jimenez J, Chiang DY, Signoretti S, Kaelin WG, Spardy N, Hahn WC, Hoshida Y, Ogino S, Depinho RA, Chin L, Garraway LA, Fuchs CS, Baselga J, Tabernero J, Gabriel S, Lander ES, Getz G, Meyerson M Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion Nature Genetics 2011 Sep 1,3,6 Colorectal cancer Next Generation Sequencing Homo sapiens CRC-3 Illumina GA-II chr10:0-129527237:0;chr10:129527238-129783714:-1;chr10:129783715-135374737:0;chr11:0-134452384:0;chr12:0-132349534:0;chr13:0-114142980:0;chr14:0-106368585:0;chr15:0-100338915:0;chr16:0-5683448:0;chr16:5683449-5776175:-1;chr16:5776176-6331356:0;chr16:6331357-7095068:-1;chr16:6523054-6622896:-1;chr16:6749075-6769575:-1;chr16:6860343-6889417:-1;chr16:7095069-88827254:0;chr17:0-78774742:0;chr18:0-76117153:0;chr19:0-63811651:0;chr1:0-10754997:0;chr1:10754998-10897669:1;chr1:10897670-49446321:0;chr1:245318786-245412605:-1;chr1:245412606-247249719:0;chr1:49446322-49489944:-1;chr1:49489945-245318785:0;chr20:0-15034058:0;chr20:15034059-15057086:-1;chr20:15057087-62435964:0;chr21:0-46944323:0;chr22:0-49691432:0;chr2:0-57109388:0;chr2:57109389-57145561:-1;chr2:57145562-242951149:0;chr3:0-2683189:0;chr3:2683190-2761783:1;chr3:2761784-4787249:0;chr3:4787250-4815954:-1;chr3:4815955-5951263:0;chr3:5951264-5988489:-1;chr3:5988490-6559790:0;chr3:60213356-60616233:-1;chr3:60532986-60541605:1;chr3:60616234-199501827:0;chr3:6559791-7177138:1;chr3:6737767-7245547:1;chr3:6796695-6825146:-1;chr3:7245548-60213355:0;chr4:0-189926790:0;chr4:189926791-189997001:-1;chr4:189997002-190416475:0;chr4:190416476-190601298:-1;chr4:190601299-191273063:0;chr5:0-178065039:0;chr5:178065040-178899590:-1;chr5:178899591-180857866:0;chr6:0-39862556:0;chr6:39862557-40074147:-1;chr6:40074148-170899992:0;chr7:0-110547180:0;chr7:110547181-110729058:-1;chr7:110724998-110927085:1;chr7:110927086-158821424:0;chr8:0-120453229:0;chr8:120453230-120750651:-1;chr8:120750652-123860546:0;chr8:123860547-123862069:-1;chr8:123862070-128170552:0;chr8:128170553-128473966:1;chr8:128473967-146274826:0;chr9:0-10517408:0;chr9:10517409-10571170:1;chr9:10571171-26169649:0;chr9:26169650-26330710:-1;chr9:26330711-140273252:0;chrX:0-154913754:0;chrY:0-57772954:0 hs1:224945390-224945390,hs1:233909251-233909251;hs1:240378413-240378413,hs1:245369879-245369879;hs1:224945525-224945525,hs1:233870037-233870037;hs1:233923401-233923401,hs1:236536122-236536122;hs1:236231922-236231922,hs1:237182872-237182872;hs1:245475793-245475793,hs3:5894391-5894391;hs1:236419236-236419236,hs3:5566303-5566303;hs1:235922389-235922389,hs3:4611675-4611675;hs1:235918361-235918361,hs3:11080171-11080171;hs1:5466610-5466610,hs3:7316755-7316755;hs1:233632828-233632828,hs3:5932076-5932076;hs1:236254591-236254591,hs3:5170554-5170554;hs1:5275710-5275710,hs3:5187100-5187100;hs1:5303622-5303622,hs3:8282035-8282035;hs1:236845686-236845686,hs3:10925011-10925011;hs1:245408838-245408838,hs3:2802655-2802655;hs1:237185816-237185816,hs3:8016594-8016594;hs1:5301538-5301538,hs3:6054295-6054295;hs1:233714631-233714631,hs3:6880142-6880142;hs1:245349054-245349054,hs3:3585460-3585460;hs1:224875793-224875793,hs3:3145867-3145867;hs1:236540834-236540834,hs3:2921314-2921314;hs1:224887091-224887091,hs3:3721322-3721322;hs1:235853269-235853269,hs3:6891109-6891109;hs1:233787690-233787690,hs3:3273593-3273593;hs1:235861396-235861396,hs3:8292875-8292875;hs1:244869048-244869048,hs3:7582747-7582747;hs1:233862655-233862655,hs5:178278887-178278887;hs1:245288005-245288005,hs5:178130481-178130481;hs2:53628330-53628330,hs2:53629451-53629451;hs2:60636921-60636921,hs2:60639951-60639951;hs2:151790755-151790755,hs9:135957853-135957853;hs3:6566468-6566468,hs3:7578764-7578764;hs3:3795729-3795729,hs3:5546204-5546204;hs3:2897939-2897939,hs3:6212189-6212189;hs3:2853112-2853112,hs3:5935342-5935342;hs3:5911194-5911194,hs3:7354302-7354302;hs3:2702507-2702507,hs3:8331278-8331278;hs3:3234820-3234820,hs3:6876658-6876658;hs3:3777596-3777596,hs3:3813752-3813752;hs3:5184088-5184088,hs3:7710801-7710801;hs3:4828423-4828423,hs3:7072509-7072509;hs3:2848467-2848467,hs3:7050326-7050326;hs3:6017124-6017124,hs3:7294182-7294182;hs3:10830132-10830132,hs5:178740539-178740539;hs3:3420430-3420430,hs5:178084387-178084387;hs3:6263160-6263160,hs5:178758089-178758089;hs3:6987679-6987679,hs5:178930532-178930532;hs5:132903613-132903613,hs5:133396590-133396590;hs5:87253239-87253239,hs8:91569923-91569923;hs5:171852562-171852562,hs9:106961714-106961714;hs6:27910367-27910367,hs6:106918619-106918619;hs6:66391721-66391721,hs6:75299704-75299704;hs6:127469925-127469925,hs6:128781514-128781514;hs6:42219015-42219015,hs6:106314863-106314863;hs6:27343409-27343409,hs6:108122202-108122202;hs6:51486682-51486682,hs6:53732426-53732426;hs6:65842350-65842350,hs6:106542981-106542981;hs6:75292810-75292810,hs6:104494212-104494212;hs6:44587618-44587618,hs6:65789992-65789992;hs6:42007977-42007977,hs6:107965922-107965922;hs6:25748686-25748686,hs6:41403970-41403970;hs6:64543890-64543890,hs6:107883335-107883335;hs6:25214697-25214697,hs6:27085335-27085335;hs6:27858841-27858841,hs6:106939044-106939044;hs6:34975611-34975611,hs6:106940055-106940055;hs6:41068797-41068797,hs6:49850765-49850765;hs6:41989443-41989443,hs6:51716875-51716875;hs6:51799583-51799583,hs6:52648225-52648225;hs6:25188883-25188883,hs6:108126806-108126806;hs6:25200375-25200375,hs6:106934554-106934554;hs6:26432414-26432414,hs6:107228180-107228180;hs6:27301141-27301141,hs6:42271311-42271311;hs6:27763751-27763751,hs6:36305598-36305598;hs6:34533687-34533687,hs6:107337718-107337718;hs6:36280941-36280941,hs6:44076259-44076259;hs6:38222706-38222706,hs6:40183593-40183593;hs6:39865154-39865154,hs6:105413847-105413847;hs6:40017876-40017876,hs6:49266572-49266572;hs6:41792828-41792828,hs6:58797510-58797510;hs6:42150556-42150556,hs6:107161417-107161417;hs6:127469928-127469928,hs6:128781518-128781518;hs6:43747579-43747579,hs6:106932132-106932132;hs6:42328572-42328572,hs6:65141693-65141693;hs6:40441124-40441124,hs6:54387076-54387076;hs6:25774577-25774577,hs6:46056103-46056103;hs6:33209107-33209107,hs6:107004069-107004069;hs6:39521662-39521662,hs6:107849873-107849873;hs6:50600569-50600569,hs6:53546383-53546383;hs6:55600617-55600617,hs6:63329817-63329817;hs6:33418159-33418159,hs6:107985099-107985099;hs7:65024392-65024392,hs7:153522286-153522286;hs7:153522268-153522268,hs8:76589412-76589412;hs10:19393206-19393206,hs10:19397392-19397392;hs16:27857950-27857950,hs16:31733613-31733613;hs16:34872868-34872868,hs16:46364585-46364585;hs22:27395596-27395596,hsX:92926657-92926657;hs22:27395907-27395907,hsX:92926675-92926675; AGBL4;AIM1;ANKS1A;ARL8B;ASB3;ATG5;B3GALNT2;BRPF3;BYSL;C1orf127;C1orf229;C6orf132;C6orf223;C6orf41;CASZ1;CDC5L;CLIC5;CMAH;CNST;CNTN4;COL12A1;CRBN;DAAM2;EDEM1;EYS;FHIT;GCLC;GNG4;GRM7;GUCA1B;GUSBL2;HACE1;HIST1H2AK;HIST1H2BL;HIST1H4H;HMGCLL1;ITPKB;ITPR1;KHDRBS2;KIF6;LMCD1;LOC146481;LOC339535;LOC553137;LRRC1;LRRN1;LYPLA2P1;LYST;MED20;MOCS1;MRPS18A;MUT;NCR2;NPHP4;PACSIN1;PDSS2;PGK2;PKHD1;PLD5;PRDM1;PRSS16;QRSL1;RSPO3;RTN4IP1;RYR2;SCGN;SCML4;SLC6A1;SLC6A11;SOBP;TAF8;TBCE;TDRG1;TFAP2D;TFEB;TINAG;TMEM14A;TRERF1;TRNT1;UNC5CL;VN1R5;ZFAND3;ZNF124;ZNF669;ZNF670;ZP4; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7x and 31.9x coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with beta-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 beta-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events. NCBI 36/hg18 phs000374 Yes ARL8B,GRM7;B3GALNT2,GRM7;BRPF3,C6orf223;BYSL,SOBP;CNTN4,GRM7;EYS,PDSS2;GRM7,RUFY1;ITPKB,GNG4;ITPR1,GRM7;KIF6,PDSS2;MED20,PKHD1;PKHD1,TMEM14A;RYR2,GRM7;SCGN,CLIC5;TRERF1,EYS CTDB0365 Research 21892161 Bass AJ, Lawrence MS, Brace LE, Ramos AH, Drier Y, Cibulskis K, Sougnez C, Voet D, Saksena G, Sivachenko A, Jing R, Parkin M, Pugh T, Verhaak RG, Stransky N, Boutin AT, Barretina J, Solit DB, Vakiani E, Shao W, Mishina Y, Warmuth M, Jimenez J, Chiang DY, Signoretti S, Kaelin WG, Spardy N, Hahn WC, Hoshida Y, Ogino S, Depinho RA, Chin L, Garraway LA, Fuchs CS, Baselga J, Tabernero J, Gabriel S, Lander ES, Getz G, Meyerson M Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion Nature Genetics 2011 Sep 4,8,16,20 Colorectal cancer Next Generation Sequencing Homo sapiens CRC-4 Illumina GA-II chr10:0-133602378:0;chr10:133602379-133603110:-1;chr10:133603111-135374737:0;chr11:0-134452384:0;chr12:0-132349534:0;chr13:0-114142980:0;chr14:0-106368585:0;chr15:0-100338915:0;chr16:0-46478965:0;chr16:46478966-46479751:-1;chr16:46479752-88827254:0;chr17:0-78774742:0;chr18:0-3252927:0;chr18:3252928-3667075:-1;chr18:3667076-76117153:0;chr19:0-63811651:0;chr1:0-247249719:0;chr20:0-18951205:0;chr20:18951206-18954029:1;chr20:18954030-23952550:0;chr20:23952551-23954112:-1;chr20:23954113-62435964:0;chr21:0-46944323:0;chr22:0-49691432:0;chr2:0-125106623:0;chr2:125106624-125349147:-1;chr2:125349148-242951149:0;chr3:0-199501827:0;chr4:0-14254204:0;chr4:127937758-127945196:-1;chr4:127945197-191273063:0;chr4:14254205-14874661:-1;chr4:14874662-60044608:0;chr4:60044609-60059497:1;chr4:60059498-97533520:0;chr4:97533521-97617439:-1;chr4:97617440-127937757:0;chr5:0-180857866:0;chr6:0-48438106:0;chr6:48438107-48604253:-1;chr6:48604254-170899992:0;chr7:0-153554788:0;chr7:153554789-153709348:-1;chr7:153709349-158821424:0;chr8:0-41184493:0;chr8:137736983-138443498:-1;chr8:138443499-146274826:0;chr8:41184494-41861964:-1;chr8:41861965-52186318:0;chr8:52186319-52186587:-1;chr8:52186588-137736982:0;chr9:0-140273252:0;chrX:0-154913754:0;chrY:0-57772954:0 hs18:56258628-56258628,hs18:58362793-58362793;hs18:44496014-44496014,hs18:57443167-57443167;hs18:45023683-45023683,hs18:58380361-58380361;hs8:37328910-37328910,hs20:9561906-9561906;hs8:35575394-35575394,hs20:36595752-36595752;hs20:11072897-11072897,hs20:18064337-18064337;hs20:18085103-18085103,hs20:37021184-37021184;hs8:35357822-35357822,hs8:40866668-40866668;hs20:11078572-11078572,hs20:16865475-16865475;hs8:40564418-40564418,hs8:41258684-41258684;hs8:38794152-38794152,hs20:15734259-15734259;hs8:32575936-32575936,hs20:19499614-19499614;hs20:9579492-9579492,hs20:11068460-11068460;hs8:29956507-29956507,hs8:40870381-40870381;hs8:40568862-40568862,hs8:41210874-41210874;hs8:33309871-33309871,hs20:17303124-17303124;hs8:25088587-25088587,hs20:18210598-18210598;hs8:30408156-30408156,hs20:11069502-11069502;hs20:15506293-15506293,hs20:18142088-18142088;hs20:18162173-18162173,hs20:21266868-21266868;hs8:30530516-30530516,hs8:37326190-37326190;hs20:11072781-11072781,hs20:19498233-19498233;hs20:17295462-17295462,hs20:18952001-18952001;hs20:19302660-19302660,hs20:25291885-25291885;hs8:36058467-36058467,hs8:40512207-40512207;hs8:28227333-28227333,hs20:21270719-21270719;hs8:29865798-29865798,hs20:18083453-18083453;hs8:33311546-33311546,hs20:11068323-11068323;hs4:22195633-22195633,hs16:76386760-76386760;hs8:24974004-24974004,hs8:33314079-33314079;hs8:28228387-28228387,hs8:29283557-29283557;hs8:32575153-32575153,hs20:9577156-9577156;hs5:103343225-103343225,hs5:112990395-112990395;hs20:11400256-11400256,hs20:21285670-21285670;hs8:33311815-33311815,hs20:17847854-17847854;hs8:25090475-25090475,hs8:30527338-30527338;hs8:36160000-36160000,hs20:9372180-9372180;hs8:30014989-30014989,hs8:32555657-32555657;hs8:34922223-34922223,hs8:38798886-38798886;hs20:36536910-36536910,hs20:36621390-36621390;hs8:25100854-25100854,hs8:38798630-38798630;hs8:40498457-40498457,hs8:41622567-41622567;hs8:37454709-37454709,hs20:11070889-11070889;hs8:38628449-38628449,hs8:39830749-39830749;hs8:25102333-25102333,hs20:9397869-9397869;hs20:15333991-15333991,hs20:23960108-23960108;hs5:103343228-103343228,hs5:109521576-109521576;hs8:30538770-30538770,hs8:32581683-32581683;hs8:30530225-30530225,hs20:19302099-19302099;hs20:9567639-9567639,hs20:17892276-17892276;hs4:15431666-15431666,hs4:22709584-22709584;hs4:22197860-22197860,hs16:76377794-76377794;hs8:37458596-37458596,hs20:16855593-16855593;hs14:57321226-57321226,hs21:20491241-20491241;hs8:35244643-35244643,hs8:41402287-41402287;hs16:76376882-76376882,hs16:76386047-76386047;hs4:15322903-15322903,hs16:74907715-74907715;hs4:15425543-15425543,hs4:21193396-21193396;hs4:22195631-22195631,hs16:70665402-70665402;hs8:34921160-34921160,hs20:18953496-18953496;hs11:93716656-93716656,hs11:94163529-94163529;hs11:93716665-93716665,hs11:94163527-94163527;hs8:37340845-37340845,hs8:38794493-38794493;hs16:70024265-70024265,hs16:74933305-74933305;hs4:15473705-15473705,hs4:21781015-21781015;hs4:22192981-22192981,hs16:70670202-70670202;hs3:86038783-86038783,hs3:86047882-86047882;hs2:53141964-53141964,hs13:61689111-61689111;hs4:14479438-14479438,hs4:14481964-14481964;hs4:14543570-14543570,hs16:70665240-70665240;hs10:97093914-97093914,hs20:10987822-10987822;hs8:34934614-34934614,hs20:19302106-19302106;hs20:11064575-11064575,hs20:25287646-25287646;hs16:74937229-74937229,hs16:76382447-76382447;hs10:97093694-97093694,hs20:10987662-10987662;hs8:40398218-40398218,hs20:36806255-36806255;hs7:124026928-124026928,hs14:58290310-58290310 ABCC12;ABHD12;ACTR5;ANK1;ASB3;BTBD3;C1QTNF7;CD38;CNTNAP4;CPEB2;CSRP2BP;DHX35;DOCK5;DUSP4;FAM135B;FUT10;GBA3;GGTLC1;GOLGA7;GPR125;HPR;IDO1;INTU;JAG1;KHDRBS3;LOC286135;LPHN3;MACROD2;NEFL;NKX6-3;NRG1;OTOR;PAK7;PCSK2;PDHA2;PET117;PLCB4;PNOC;PXDNL;RALGAPB;RBPMS;RNF5P1;SFRP1;SLC24A3;SNX5;TACC1;TMEM66;TXNL4B;UNC5D;VAT1L;XRN2;ZMAT4;ZNF133;ZNF23;ZNF703; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7x and 31.9x coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with beta-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 beta-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events. NCBI 36/hg18 phs000374 Yes BST1,CNTNAP4;CD38,KCNIP4;CNTNAP4,VAT1L;DOCK5,PLCB4;NRG1,PAK7;NRG1,SLC24A3;RBPMS,SLC24A3;SLC24A3,ABHD12;TACC1,MACROD2;UNC5D,RALGAPB CTDB0366 Research 21892161 Bass AJ, Lawrence MS, Brace LE, Ramos AH, Drier Y, Cibulskis K, Sougnez C, Voet D, Saksena G, Sivachenko A, Jing R, Parkin M, Pugh T, Verhaak RG, Stransky N, Boutin AT, Barretina J, Solit DB, Vakiani E, Shao W, Mishina Y, Warmuth M, Jimenez J, Chiang DY, Signoretti S, Kaelin WG, Spardy N, Hahn WC, Hoshida Y, Ogino S, Depinho RA, Chin L, Garraway LA, Fuchs CS, Baselga J, Tabernero J, Gabriel S, Lander ES, Getz G, Meyerson M Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion Nature Genetics 2011 Sep 5,11,X Colorectal cancer Next Generation Sequencing Homo sapiens CRC-6 Illumina GA-II chr10:0-135374737:0;chr11:0-134452384:0;chr12:0-132349534:0;chr13:0-114142980:0;chr14:0-76714076:0;chr14:76714077-76720824:1;chr14:76720825-106368585:0;chr15:0-100338915:0;chr16:0-6526414:0;chr16:6526415-6960093:-1;chr16:6708036-6921294:-1;chr16:6960094-71296250:0;chr16:71296251-71581646:-1;chr16:71581647-88827254:0;chr17:0-78774742:0;chr18:0-76117153:0;chr19:0-63811651:0;chr1:0-247249719:0;chr20:0-14461407:0;chr20:14461408-15021576:-1;chr20:15021577-15267859:0;chr20:15267860-15450481:1;chr20:15450482-62435964:0;chr21:0-46944323:0;chr22:0-49691432:0;chr2:0-242951149:0;chr3:0-59959992:0;chr3:176312186-176314409:1;chr3:176314410-199501827:0;chr3:59959993-59994869:1;chr3:59994870-60693023:0;chr3:60693024-60995416:-1;chr3:60995417-176312185:0;chr4:0-92475037:0;chr4:92475038-92502563:-1;chr4:92502564-92535698:0;chr4:92535699-92625911:-1;chr4:92625912-191273063:0;chr5:0-180857866:0;chr6:0-170899992:0;chr7:0-158821424:0;chr8:0-9981487:0;chr8:10335595-146274826:0;chr8:9981488-10335594:-1;chr9:0-4573927:0;chr9:4573928-4674674:-1;chr9:4674675-140273252:0;chrX:0-7459933:0;chrX:142336499-142429682:1;chrX:142429683-154913754:0;chrX:7459934-7568488:-1;chrX:7568489-142336498:0;chrY:0-57772954:0 hs5:158747640-158747640,hs11:68093742-68093742;hsX:104863865-104863865,hsX:142403712-142403712;hs5:98134842-98134842,hs11:58106127-58106127;hs18:44926172-44926172,hs18:46013514-46013514;hsX:86058035-86058035,hsX:124825414-124825414;hs5:98214924-98214924,hs5:157876135-157876135;hs1:191671679-191671679,hs1:191819910-191819910;hs5:122741029-122741029,hs5:159744189-159744189;hs5:122736211-122736211,hs11:130217878-130217878;hsX:25613574-25613574,hsX:107742244-107742244;hs5:125637905-125637905,hs11:130222298-130222298;hs5:103605949-103605949,hs11:95790285-95790285;hsX:122937829-122937829,hsX:142348044-142348044;hs5:122741036-122741036,hs5:125720100-125720100;hs5:122723838-122723838,hs11:130217949-130217949;hs18:46013512-46013512,hs18:53897496-53897496;hsX:49011736-49011736,hsX:64251170-64251170;hsX:55048491-55048491,hsX:122967449-122967449;hs1:191671680-191671680,hs1:191819913-191819913;hs5:96606058-96606058,hs5:123104889-123104889;hs5:103599978-103599978,hs5:153955365-153955365;hs5:96226634-96226634,hs11:100153009-100153009;hs5:103600037-103600037,hs11:94602050-94602050;hsX:53497999-53497999,hsX:69698863-69698863;hsX:79853797-79853797,hsX:85382306-85382306;hs5:122715537-122715537,hs11:68093742-68093742;hsX:29401569-29401569,hsX:122937035-122937035;hsX:58517184-58517184,hsX:110740735-110740735;hs5:114954407-114954407,hs5:125721276-125721276;hs5:122717021-122717021,hs5:123100394-123100394;hs5:123100570-123100570,hs11:95790329-95790329;hs5:159754284-159754284,hs11:63010998-63010998;hsX:63121602-63121602,hsX:64301050-64301050;hsX:115120846-115120846,hsX:142336327-142336327;hs5:114954403-114954403,hs5:153955467-153955467;hs5:123049468-123049468,hs5:132655097-132655097;hs5:123105121-123105121,hs5:159778023-159778023;hs5:123116543-123116543,hs5:150142920-150142920;hs11:58100154-58100154,hs11:60132932-60132932;hs16:6653874-6653874,hs16:7661265-7661265;hs5:122747926-122747926,hs5:123116614-123116614;hsX:67379720-67379720,hsX:122967037-122967037;hs5:123049810-123049810,hs5:132586703-132586703;hsX:56077983-56077983,hsX:142404171-142404171;hs5:103605990-103605990,hs11:130254634-130254634;hs5:153429264-153429264,hs11:95785181-95785181;hs8:36536789-36536789,hs8:36560279-36560279;hsX:48961667-48961667,hsX:75688815-75688815;hsX:75666948-75666948,hsX:107732123-107732123;hsX:48810100-48810100,hsX:142347898-142347898;hs8:127318815-127318815,hs8:129338694-129338694;hsX:48784377-48784377,hsX:65938205-65938205;hs1:200980692-200980692,hs3:66383929-66383929;hs5:122756417-122756417,hs11:100152883-100152883;hs17:19246777-19246777,hs17:19257957-19257957;hsX:69735999-69735999,hsX:142429612-142429612;hsX:75678097-75678097,hsX:104732644-104732644;hsX:48978268-48978268,hsX:85346286-85346286;hs8:41693481-41693481,hs8:41694385-41694385;hs8:43103766-43103766,hs8:60011734-60011734 AGTR2;ALG13;APEX2;BRWD3;C11orf64;C5orf54;C5orf62;CACNA1F;CCDC120;CCDC22;CEP120;CHD1;COL4A5;CSNK1G3;DACH2;DCAF12L2;EBF1;EDA2R;ERAP2;FLJ32810;FSTL4;GRAMD3;HRASLS5;HSD17B10;IL1RAPL1;IL1RAPL2;JRKL;KLF8;LARP1;LPXN;MAGEB18;MAGEE1;MFAP3;MIR1468;NUDT12;OPHN1;PPP1R3F;RGMB;RIOK2;SAPS3;SESN3;SLU7;SNX19;SPANXN3;STAG2;TEX11;TFE3;TMED7-TICAM2;VCX;ZC4H2;ZFP91;ZXDA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7x and 31.9x coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with beta-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 beta-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events. NCBI 36/hg18 phs000374 Yes APEX2,STAG2;C5orf54,HRASLS5;CCDC22,DACH2;CEP120,FLJ32810;CEP120,SAPS3;IL1RAPL1,STAG2;OPHN1,STAG2;RGMB,ZFP91;TEX11,SPANXN3;TMED7,GRAMD3 CTDB0367 Research 23583981 Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I, Boop FA, Lu C, Kandoth C, Ding L, Lee R, Huether R, Chen X, Hedlund E, Nagahawatte P, Rusch M, Boggs K, Cheng J, Becksfort J, Ma J, Song G, Li Y, Wei L, Wang J, Shurtleff S, Easton J, Zhao D, Fulton RS, Fulton LL, Dooling DJ, Vadodaria B, Mulder HL, Tang C, Ochoa K, Mullighan CG, Gajjar A, Kriwacki R, Sheer D, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Baker SJ, Ellison DW; St. Jude Children's Research Hospital -Washington University Pediatric Cancer Genome Project Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas Nature Genetics 2013 Jun 5,6 Glioma Next Generation Sequencing Homo sapiens SJLGG005 Illumina Genome Analyzer IIx or HighSeq chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-104635198:0;chr6:104635199-135517619:-1;chr6:135517620-171115067:0;chr7:0-159138663:0;chr8:0-146364022:0;chr9:0-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs5:140843463-140843463,hs6:104664174-104664174;hs6:135517564-135517564,hs5:140857801-140857801 PCDHGB1;MYB Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA The most common pediatric brain tumors are low-grade gliomas (LGGs). We used whole-genome sequencing to identify multiple new genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24 of 39 (62%) tumors. Intragenic duplications of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes expressing FGFR1 with the duplication involving the TKD into the brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. FGFR1 with the duplication induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs and LGGNTs. GRCh37/hg19 Yes NA CTDB0368 Research 23583981 Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I, Boop FA, Lu C, Kandoth C, Ding L, Lee R, Huether R, Chen X, Hedlund E, Nagahawatte P, Rusch M, Boggs K, Cheng J, Becksfort J, Ma J, Song G, Li Y, Wei L, Wang J, Shurtleff S, Easton J, Zhao D, Fulton RS, Fulton LL, Dooling DJ, Vadodaria B, Mulder HL, Tang C, Ochoa K, Mullighan CG, Gajjar A, Kriwacki R, Sheer D, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Baker SJ, Ellison DW; St. Jude Children's Research Hospital -Washington University Pediatric Cancer Genome Project Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas Nature Genetics 2013 Jun 8 Glioma Next Generation Sequencing Homo sapiens SJLGG033 Illumina Genome Analyzer IIx or HighSeq chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-67490865:0;chr8:67490866-89031536:1;chr8:69654188-67490578:1;chr8:78562383-89031728:-1;chr8:82753337-69654563:1;chr8:89031729-146364022:0;chr9:0-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs8:78562409-78562409,hs8:82753859-82753859 C8orf34;MYBL1;SNX16 Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA The most common pediatric brain tumors are low-grade gliomas (LGGs). We used whole-genome sequencing to identify multiple new genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24 of 39 (62%) tumors. Intragenic duplications of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes expressing FGFR1 with the duplication involving the TKD into the brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. FGFR1 with the duplication induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs and LGGNTs. GRCh37/hg19 Yes C8orf34,MYBL1 CTDB0369 Research 23583981 Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I, Boop FA, Lu C, Kandoth C, Ding L, Lee R, Huether R, Chen X, Hedlund E, Nagahawatte P, Rusch M, Boggs K, Cheng J, Becksfort J, Ma J, Song G, Li Y, Wei L, Wang J, Shurtleff S, Easton J, Zhao D, Fulton RS, Fulton LL, Dooling DJ, Vadodaria B, Mulder HL, Tang C, Ochoa K, Mullighan CG, Gajjar A, Kriwacki R, Sheer D, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Baker SJ, Ellison DW; St. Jude Children's Research Hospital -Washington University Pediatric Cancer Genome Project Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas Nature Genetics 2013 Jun 6 Glioma Next Generation Sequencing Homo sapiens SJLGG035 Illumina Genome Analyzer IIx or HighSeq chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-135491704:0;chr6:135491705-136884680:-1;chr6:136882615-135495476:1;chr6:136884681-171115067:0;chr7:0-159138663:0;chr8:0-146364022:0;chr9:0-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs6:135540965-135540965,hs8:89335432-89335432;hs8:88417780-88417780,hs6:136741489-136741489 MAP3K5;MAP7;MMP16; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA The most common pediatric brain tumors are low-grade gliomas (LGGs). We used whole-genome sequencing to identify multiple new genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24 of 39 (62%) tumors. Intragenic duplications of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes expressing FGFR1 with the duplication involving the TKD into the brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. FGFR1 with the duplication induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs and LGGNTs. GRCh37/hg19 Yes NA CTDB0370 Research 23583981 Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I, Boop FA, Lu C, Kandoth C, Ding L, Lee R, Huether R, Chen X, Hedlund E, Nagahawatte P, Rusch M, Boggs K, Cheng J, Becksfort J, Ma J, Song G, Li Y, Wei L, Wang J, Shurtleff S, Easton J, Zhao D, Fulton RS, Fulton LL, Dooling DJ, Vadodaria B, Mulder HL, Tang C, Ochoa K, Mullighan CG, Gajjar A, Kriwacki R, Sheer D, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Baker SJ, Ellison DW; St. Jude Children's Research Hospital -Washington University Pediatric Cancer Genome Project Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas Nature Genetics 2013 Jun 9 Glioma Next Generation Sequencing Homo sapiens SJLGG038 Illumina Genome Analyzer IIx or HighSeq chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-146364022:0;chr9:0-14731423:0;chr9:14731424-78562970:-1;chr9:21749091-22015572:-1;chr9:22024624-22025145:-1;chr9:37804215-37804296:-1;chr9:78559926-78663080:-1;chr9:78654643-36070277:1;chr9:78663081-78671456:0;chr9:78671457-89348568:-1;chr9:84653505-78666783:1;chr9:89340180-78518260:1;chr9:89348569-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs9:78566224-78566224,hs9:116237623-116237623;hs9:89337633-89337633,hs9:78583405-78583405;hs12:12018549-12018549,hs15:88646889-88646889;hs12:12018559-12018559,hs15:88646886-88646886 CDKN2B-AS1;ETV6;NTRK3;PCSK5;RECK; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA The most common pediatric brain tumors are low-grade gliomas (LGGs). We used whole-genome sequencing to identify multiple new genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24 of 39 (62%) tumors. Intragenic duplications of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes expressing FGFR1 with the duplication involving the TKD into the brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. FGFR1 with the duplication induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs and LGGNTs. GRCh37/hg19 Yes PCSK5,RECK CTDB0371 Research 23583981 Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I, Boop FA, Lu C, Kandoth C, Ding L, Lee R, Huether R, Chen X, Hedlund E, Nagahawatte P, Rusch M, Boggs K, Cheng J, Becksfort J, Ma J, Song G, Li Y, Wei L, Wang J, Shurtleff S, Easton J, Zhao D, Fulton RS, Fulton LL, Dooling DJ, Vadodaria B, Mulder HL, Tang C, Ochoa K, Mullighan CG, Gajjar A, Kriwacki R, Sheer D, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Baker SJ, Ellison DW; St. Jude Children's Research Hospital -Washington University Pediatric Cancer Genome Project Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas Nature Genetics 2013 Jun 1,3,11,12 Glioma Next Generation Sequencing Homo sapiens SJLGG039 Illumina Genome Analyzer IIx or HighSeq chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-12649233:0;chr3:12649234-46001511:-1;chr3:46001512-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-9539556:0;chr7:6300099-159138663:0;chr7:9539557-6300098:1;chr8:0-146364022:0;chr9:0-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs1:3643330-3643330,hs11:115411715-115411715;hs1:3643581-3643581,hs11:69538645-69538645;hs1:3649438-3649438,hs22:47557135-47557135;hs1:12582471-12582471,hs12:103110023-103110023;hs1:12584121-12584121,hs11:118491727-118491727;hs3:49168971-49168971,hs11:66966686-66966686;hs3:186716601-186716601,hs4:1899271-1899271;hs4:5039611-5039611,hs3:183723574-183723574;hs10:98887882-98887882,hs16:2158836-2158836;hs11:69540077-69540077,hs1:9555182-9555182;hs11:69541460-69541460,hs12:103111315-103111315;hs12:103110079-103110079,hs10:95588803-95588803;hs12:103112184-103112184,hs3:9662023-9662023;hs12:106295961-106295961,hs1:12581667-12581667;hs16:410315-410315,hs4:5037703-5037703;hs16:2170637-2170637,hs12:103110956-103110956;hs16:2172065-2172065,hs1:1196437-1196437 ABCC5;CYTH3;FYCO1;KDM2A;PHLDB1;PKD1;RAF1;SLIT1;ST6GAL1;TP73;UBE2J2;WHSC1; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA The most common pediatric brain tumors are low-grade gliomas (LGGs). We used whole-genome sequencing to identify multiple new genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24 of 39 (62%) tumors. Intragenic duplications of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes expressing FGFR1 with the duplication involving the TKD into the brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. FGFR1 with the duplication induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs and LGGNTs. GRCh37/hg19 Yes FYCO1,RAF1;ST6GAL1,WHSC1;UBE2J2,PKD1 CTDB0377 Research 24413735 Papaemmanuil E, Rapado I, Li Y, Potter NE, Wedge DC, Tubio J, Alexandrov LB, Van Loo P, Cooke SL, Marshall J, Martincorena I, Hinton J, Gundem G, van Delft FW5, Nik-Zainal S, Jones DR, Ramakrishna M, Titley I, Stebbings L, Leroy C, Menzies A, Gamble J, Robinson B, Mudie L, Raine K, O'Meara S, Teague JW, Butler AP, Cazzaniga G, Biondi A, Zuna J, Kempski H, Muschen M, Ford AM, Stratton MR, Greaves M, Campbell PJ RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia Nature Genetics 2014 Feb X Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens PD4021a Illumina GAIIx chr10:0-111767206:0;chr10:111767207-111868993:-1;chr10:111868994-135534747:0;chr11:0-36619637:0;chr11:36619638-36641928:-1;chr11:36641929-135006516:0;chr12:0-133851895:0;chr13:0-79741019:0;chr13:79741020-80622777:-1;chr13:80622778-115169878:0;chr14:0-20535558:0;chr14:20535559-20669165:1;chr14:20669166-93785332:0;chr14:93785333-93798624:-1;chr14:93798625-107349540:0;chr15:0-102531392:0;chr16:0-81913021:0;chr16:81913022-82023811:-1;chr16:82023812-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-241650825:0;chr1:241650826-241656688:-1;chr1:241656689-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-176913895:0;chr3:176913896-177100751:-1;chr3:177100752-198022430:0;chr4:0-96032247:0;chr4:96032248-96078844:-1;chr4:96078845-191154276:0;chr5:0-22951246:0;chr5:22951247-23013377:-1;chr5:23013378-180915260:0;chr6:0-171115067:0;chr7:0-136958304:0;chr7:136958305-139011263:-1;chr7:139011264-159138663:0;chr8:0-146364022:0;chr9:0-141213431:0;chrX:0-6249420:0;chrX:105962256-109139512:1;chrX:10852341-24782792:1;chrX:120451702-155270560:0;chrX:51132045-74233382:-1;chrX:6249421-11552024:-1;chrX:62711496-104787984:-1;chrX:65752070-67144086:-1;chrX:6669959-107350305:1;chrX:74235850-76566878:-1;chrX:76567692-105963715:1;chrX:76568085-120451701:1;chrY:0-59373566:0 hs1:241650826-241650926,hs1:241656588-241656688;hs3:176913896-176913996,hs3:177100651-177100751;hs4:96032248-96032348,hs4:96078744-96078844;hs5:22951247-22951347,hs5:23013277-23013377;hs7:136958305-136958405,hs7:139011163-139011263;hs10:111767207-111767307,hs10:111868893-111868993;hs11:36619638-36619738,hs11:36641828-36641928;hs13:79741020-79741120,hs13:80622677-80622777;hs14:93785333-93785433,hs14:93798524-93798624;hs16:81913022-81913122,hs16:82023711-82023811;hsX:6249421-6249521,hsX:11551924-11552024;hsX:51132045-51132145,hsX:74233282-74233382;hsX:62711496-62711596,hsX:104787884-104787984;hsX:65752070-65752170,hsX:67143986-67144086;hsX:74235850-74235950,hsX:76566778-76566878 ABCB7;AC002359;AC002365;AC002366;AC002504;AC002981;AC003658;AC003666;AC003684;AC004073;AC004074;AC004386;AC004478;AC004673;AC004998;AC005023;AC005926;AC006062;AC006144;AC008162;AC073488;AC073597;AC073909;AC078993;AC092198;AC112497;AC112778;AC115617;AC117517;AC121344;AC233283;ACA64;ACE2;ACOT9;ACRC;ACSL4;ACTBP1;ACTG1P10;ACTR3P2;AF196779;AF196969;AF196970;AF196972;AF207550;AF238380;AF241726;AGTR2;AKAP14;AKAP16B;AKAP4;AKR1B1P8;AL008708;AL009172;AL022165;AL031115;AL031311;AL035088;AL035422;AL035427;AL035494;AL049610;AL078580;AL096700;AL109750;AL121578;AL121869;AL133512;AL135749;AL136137;AL137845;AL138891;AL139396;AL139809;AL158141;AL158819;AL159987;AL161723;AL161779;AL353691;AL353698;AL353999;AL355852;AL357752;AL359079;AL360224;AL390840;AL390966;AL391315;AL391358;AL391803;AL391821;AL445236;AL445467;AL445523;AL451005;AL513007;AL590069;AL590240;AL590285;AL590407;AL590410;AL590762;AL590763;AL590808;AL591378;AL591394;AL591708;AL592043;AL596268;AL627402;AL670379;AL672138;AL732366;AL772208;AL772284;AL928646;AL929101;ALAS2;ALG13;AMELX;AMMECR1;AMOT;ANKRD58;AP1S2;APEX2;API5P1;APOO;APOOL;AR;ARAF;ARHGAP6;ARHGEF9;ARL13A;ARMCX1;ARMCX2;ARMCX3;ARMCX4;ARMCX5;ARMCX6;ARR3;ARX;ASB11;ASB12;ASB9;ASS1P5;ATG4A;ATP1B4;ATP6AP2;ATP7A;ATRX;ATXN3L;AWAT1;AWAT2;BCOR;BEND2;BEX1;BEX2;BEX4;BEX5;BHLHB9;BMP15;BMP2KL;BMX;BRWD3;BTF3P8;BTK;BX119917;BX119964;BX276092;BX682235;BX842568;C11orf74;C1GALT1C1;CA5B;CA5BP;CACNA1F;CAPN6;CASK;CBX1P1;CBX1P2;CBX1P4;CCDC120;CCDC22;CCNB3;CCT4P2;CDK16;CDKL5;CDX4;CENPI;CENPVL1;CFP;CHIC1;CHM;CHRDL1;CHST7;CITED1;CKS1BP6;CLCN4;CLCN5;CLDN2;CNKSR2;COL4A5;COL4A6;COX7B;CPXCR1;CSTF2;CT47A1;CT47A10;CT47A11;CT47A2;CT47A3;CT47A4;CT47A5;CT47A6;CT47A7;CT47A8;CT47A9;CT47B1;CTD-2225F20;CTD-2230M5;CTD-2234B20;CTD-2267G17;CTD-2522E6;CTD-2542O7;CTPS2;CUL4B;CXCR3;CXorf21;CXorf22;CXorf23;CXorf24;CXorf26;CXorf27;CXorf29;CXorf30;CXorf31;CXorf36;CXorf38;CXorf41;CXorf46;CXorf49;CXorf49B;CXorf56;CXorf57;CXorf58;CXorf59;CXorf61;CXorf65;CXorf67;CXXC1P1;CYBB;CYLC1;CYSLTR1;DACH2;DCAF8L1;DCAF8L2;DCX;DDX3X;DDX53;DGAT2L6;DGKK;DIAPH2;DLG3;DMD;DMRTC1;DMRTC1B;DOCK11;DRP2;DUSP21;DYNLT3;EBP;EDA;EDA2R;EEF1A1P15;EEF1A1P29;EEF1A1P30;EEF1A1P40;EEF1B4;EFHC2;EFNB1;EGFL6;EIF1AX;EIF2S3;EIF4A1P10;EIF4BP7;EIF4BP9;ERAS;ERCC6L;ERVWE2;ESX1;FAAH2;FABP5P15;FAM104B;FAM120C;FAM123B;FAM133A;FAM155B;FAM156A;FAM156B;FAM199X;FAM3C2;FAM46D;FAM47A;FAM47B;FAM47C;FAM47DP;FAM48B1;FAM48B2;FAM70A;FAM9A;FAM9B;FAM9C;FANCB;FDPSP5;FGD1;FGF16;FIGF;FOXO4;FOXP3;FOXR2;FRMPD3;FRMPD4;FTH1P14;FTH1P18;FTH1P19;FTHL17;FTLP16;FTLP2;FTSJ1;FUNDC1;FXYD8;GAGE1;GAGE10;GAGE12B;GAGE12C;GAGE12D;GAGE12E;GAGE12F;GAGE12G;GAGE12H;GAGE12I;GAGE12J;GAGE13;GAGE2A;GAGE2D;GAGE2E;GAPDHP1;GAPDHP65;GATA1;GDPD2;GEMIN8;GEMIN8P3;GHc-1077H7;GHc-210E9;GHc-362H12;GHc-602D8;GJA6P;GJB1;GK;GLA;GLOD5;GLRA2;GLRA4;GLUD1P9;GNG5P2;GNL3L;GPKOW;GPM6B;GPR143;GPR173;GPR174;GPR34;GPR64;GPR82;GPRASP1;GPRASP2;GRIPAP1;GRPR;GSPT2;GUCY2F;H2BFM;H2BFWT;HCCS;HDAC6;HDAC8;HDHD1;HDX;HEPH;HK2P1;HMGA1P1;HMGB1P12;HMGB1P15;HMGB1P16;HMGB1P32;HMGN5;HNRNPH2;HSD17B10;HSPB1P2;HTR2C;HUWE1;IGBP1;IL13RA1;IL13RA2;IL1RAPL1;IL1RAPL2;IL2RG;INE1;INGX;IQSEC2;IRS4;ITGB1BP2;ITIH5L;ITM2A;KAL1;KCND1;KCNE1L;KCTD9P2;KDM5C;KDM6A;KIAA1210;KIAA2022;KIF4A;KLF8;KLHL13;KLHL15;KLHL34;KLHL4;KRT18P49;KRT8P14;LAMP2;LANCL3;LAS1L;LDHBP2;LHFPL1;LL0XNC01-105G4;LL0XNC01-116E7;LL0XNC01-131B10;LL0XNC01-144A10;LL0XNC01-157D4;LL0XNC01-177E8;LL0XNC01-19D8;LL0XNC01-221F2;LL0XNC01-237H1;LL0XNC01-240C2;LL0XNC01-250H12;LL0XNC01-46H11;LL0XNC01-73E8;LONRF3;LPAR4;LRCH2;LUZP4;MAGEB1;MAGEB10;MAGEB16;MAGEB17;MAGEB18;MAGEB2;MAGEB3;MAGEB4;MAGEB5;MAGEB6;MAGEB6B;MAGED1;MAGED2;MAGED4;MAGED4B;MAGEE1;MAGEE2;MAGEH1;MAGIX;MAGT1;MAOA;MAOB;MAP3K15;MAP7D2;MBTPS2;MCART6;MCTS1;MED12;MED14;MID1;MID1IP1;MID2;MIR1277;MIR1298;MIR1468;MIR188;MIR1911;MIR1912;MIR221;MIR222;MIR223;MIR325;MIR361;MIR362;MIR374A;MIR374B;MIR421;MIR448;MIR500A;MIR500B;MIR501;MIR502;MIR532;MIR545;MIR548F5;MIR548I4;MIR548M;MIR651;MIR652;MIR660;MIR764;MIR766;MIR98;MIRLET7F2;MORC4;MORF4L2;MORF4LP5;MOSPD2;MRPL32P1;MRPL35P4;MRPS17P9;MSL3;MSN;MTMR8;MTND2P2;MUM1L1;MYCL2;NAP1L2;NAP1L3;NAP1L6;NCBP2L;NCRNA00182;NCRNA00183;NCRNA00246;NCRNA00269;NDP;NDUFA1;NDUFB11;NGFRAP1;NHS;NHSL2;NKAP;NKAPP1;NKRF;NLGN3;NONO;NOX1;NPM1P8;NR0B1;NRK;NUDT10;NUDT11;NUP62CL;NUS1P1;NXF2;NXF2B;NXF3;NXF4;NXF5;NXT2;NYX;OFD1;OGT;OPHN1;OTC;OTUD5;OTUD6A;P2RY10;P2RY4;PA2G4P1;PABPC1L2A;PABPC1L2B;PABPC1P3;PABPC5;PAGE1;PAGE2;PAGE2B;PAGE3;PAGE4;PAGE5;PAICSP7;PAK3;PCDH11X;PCDH19;PCSK1N;PCYT1B;PDHA1;PDK3;PDZD11;PFKFB1;PGAM4;PGK1;PGRMC1;PHEX;PHF16;PHF8;PHKA1;PHKA2;PIGA;PIM2;PIN4;PIR;PJA1;PLP1;PLP2;PLS3;PNPLA4;POF1B;POLA1;PORCN;POU3F4;PPEF1;PPP1R2P9;PPP1R3F;PQBP1;PRAF2;PRDX4;PRICKLE3;PRPS1;PRPS2;PRRG1;PSMD10;PTCHD1;PYY3;RAB40A;RAB40AL;RAB41;RAB9A;RAB9B;RAI2;RBBP7;RBM10;RBM3;RBM41;RBMXL3;REPS2;RGAG1;RGAG4;RGN;RHOXF1;RHOXF2;RHOXF2B;RIBC1;RIPPLY1;RLIM;RN28S1;RNF113A;RNF128;RNF19BPX;RNU12-2P;RNU6-50P;RNU7-56P;RNU7-7P;RP2;RP5-1000K24;RP5-1055C14;RP5-1059E7;RP5-1091N2;RP5-1100E15;RP5-1139I1;RP5-1145L23;RP5-1158B12;RP5-1158E12;RP5-1158H2;RP5-1168A5;RP5-1170D6;RP5-1172N10;RP5-1174J21;RP5-820B18;RP5-834A16;RP5-839M11;RP5-849L7;RP5-878I13;RP5-928E24;RP5-944N9;RP5-958B3;RP5-961K14;RP5-964N17;RP5-972B16;RP5-998G20;RP6-105D16;RP6-113J7;RP6-127F18;RP6-145B8;RP6-149D17;RP6-159A1;RP6-162O13;RP6-186E3;RP6-191P20;RP6-1O2;RP6-204F4;RP6-218J18;RP6-227L5;RP6-22P16;RP6-24A23;RP6-29D12;RP6-60B16;RP6-99M1;RPA4;RPGR;RPL36A;RPL39;RPL9P7;RPS15AP40;RPS26P11;RPS4X;RPS6KA3;RPS6KA6;RRAGB;RRM2P3;RS1;S100G;SALL1P1;SAR1AP4;SAT1;SATL1;SCARNA23;SCML1;SCML2;SEPT6;SERPINA7;SH3BGRL;SH3KBP1;SHC1P1;SHROOM2;SHROOM4;SIAH1L;SLC16A2;SLC25A43;SLC25A5;SLC35A2;SLC38A5;SLC6A14;SLC7A3;SLC9A7;SMC1A;SMEK3P;SMPX;SMS;SNORA11C;SNORA11D;SNORA11E;SNORA35;SNORA64;SNORA68;SNORA7;SNORA9;SNORD112;SNORD30;SNORD96B;snosnR60_Z15;snoU2_19;SNX12;SPACA5;SPACA5B;SPANXN5;SPIN2A;SPIN2B;SPIN3;SPIN4;SRIP2;SRPX;SRPX2;SSX1;SSX10;SSX2;SSX2B;SSX3;SSX4;SSX4B;SSX5;SSX6;SSX7;SSX8;SSX9;ST13P18;STARD8;STS;SUV39H1;SYAP1;SYN1;SYP;SYTL4;SYTL5;TAB3;TAF1;TAF7L;TAF9B;TBC1D25;TBC1D8B;TBL1X;TBX22;TCEAL1;TCEAL2;TCEAL3;TCEAL4;TCEAL5;TCEAL6;TCEAL7;TCEAL8;TCEANC;TDGF3;TERF1P4;TEX11;TEX13A;TEX13B;TEX16P;TFE3;TGIF2LX;TIMM17B;TIMM8A;TIMP1;TLR7;TLR8;TMEM164;TMEM27;TMEM31;TMEM35;TMEM47;TMSB15A;TMSB15B;TMSB4X;TNMD;TRAPPC2;TRMT2B;TRNAE37P;TRO;TRPC5;TSC22D3;TSPAN6;TSPAN7;TSPYL2;TSR2;TTC3P1;TXLNG;U5;U70984;UBA1;UBE2A;UBQLN2;UPF3B;UPRT;UQCRBP1;USMG5P1;USP11;USP12PX;USP27X;USP51;USP9X;UXT;VCX;VCX2;VCX3A;VCX3B;VDAC1P1;VDAC1P2;VENTXP1;VN1R110P;VSIG1;VSIG4;VTRNA3P;WAS;WBP5;WDR13;WDR44;WDR45;WNK3;WWC3;XAGE1A;XAGE1B;XAGE1C;XAGE1D;XAGE2;XAGE2B;XAGE3;XAGE5;XIST;XK;XKRX;XX-FW87585A5;XXyac-YR12DB5;Y10196;YAP1P2;YIPF6;YWHAZP7;YWHAZP8;YY2;Z68873;Z73964;Z80107;Z82216;Z83745;Z97356;Z97985;Z98304;ZBTB33;ZC3H12B;ZC4H2;ZCCHC12;ZCCHC13;ZCCHC16;ZCCHC5;ZDHHC15;ZFRP1;ZFX;ZMAT1;ZMYM3;ZNF157;ZNF182;ZNF41;ZNF630;ZNF645;ZNF673;ZNF674;ZNF711;ZNF81;ZRSR2;ZXDA;ZXDB; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK The ETV6-RUNX1 fusion gene, found in 25% of childhood acute lymphoblastic leukemia (ALL) cases, is acquired in utero but requires additional somatic mutations for overt leukemia. We used exome and low-coverage whole-genome sequencing to characterize secondary events associated with leukemic transformation. RAG-mediated deletions emerge as the dominant mutational process, characterized by recombination signal sequence motifs near breakpoints, incorporation of non-templated sequence at junctions, ~30-fold enrichment at promoters and enhancers of genes actively transcribed in B cell development and an unexpectedly high ratio of recurrent to non-recurrent structural variants. Single-cell tracking shows that this mechanism is active throughout leukemic evolution, with evidence of localized clustering and reiterated deletions. Integration of data on point mutations and rearrangements identifies ATF7IP and MGA as two new tumor-suppressor genes in ALL. Thus, a remarkably parsimonious mutational process transforms ETV6-RUNX1-positive lymphoblasts, targeting the promoters, enhancers and first exons of genes that normally regulate B cell differentiation. GRCh37/hg19 Yes NA CTDB0378 Research 25790038 Kovac M, Navas C, Horswell S, Salm M, Bardella C, Rowan A, Stares M, Castro-Giner F, Fisher R, de Bruin EC, Kovacova M, Gorman M, Makino S, Williams J, Jaeger E, Jones A, Howarth K, Larkin J, Pickering L, Gore M, Nicol DL, Hazell S, Stamp G, O'Brien T, Challacombe B, Matthews N, Phillimore B, Begum S, Rabinowitz A, Varela I, Chandra A, Horsfield C, Polson A, Tran M, Bhatt R, Terracciano L, Eppenberger-Castori S, Protheroe A, Maher E, El Bahrawy M, Fleming S, Ratcliffe P, Heinimann K, Swanton C, Tomlinson I Recurrent chromosomal gains and heterogeneous driver mutations characterise papillary renal cancer evolution Nature Communications 2015 Mar 2 Renal cancer Next Generation Sequencing Homo sapiens P09 Complete Genomics hs1:10369469-10369469,hs1:10378666-10378666;hs1:15326650-15326650,hs1:15327594-15327594;hs1:22499759-22499759,hs1:22509305-22509305;hs1:26889324-26889324,hs1:26892049-26892049;hs1:29304475-29304475,hs1:29306235-29306235;hs1:45021424-45021424,hs1:45022508-45022508;hs1:70851336-70851336,hs7:108421155-108421155;hs1:71237363-71237363,hs1:71240327-71240327;hs1:102983283-102983283,hs1:102984751-102984751;hs1:113036782-113036782,hs1:113038048-113038048;hs1:113529276-113529276,hs1:113532732-113532732;hs1:120079680-120079680,hs1:120080061-120080061;hs1:155659759-155659759,hs1:155664464-155664464;hs1:158725872-158725872,hs2:148952674-148952674;hs1:166551582-166551582,hs1:166552533-166552533;hs1:172759292-172759292,hs1:172761991-172761991;hs1:195952854-195952854,hs1:195955718-195955718;hs1:196602684-196602684,hs1:196604037-196604037;hs1:207841065-207841065,hs1:207845817-207845817;hs1:210722460-210722460,hs1:210724880-210724880;hs1:238316731-238316731,hs1:238318163-238318163;hs1:240122758-240122758,hs1:240123257-240123257;hs1:248571563-248571563,hs1:248572411-248572411;hs1:248866116-248866116,hs1:248866464-248866464;hs1:248867187-248867187,hs1:248876093-248876093;hs2:1374235-1374235,hs2:1376062-1376062;hs2:1374618-1374618,hs2:1376072-1376072;hs2:3894595-3894595,hs16:80211598-80211598;hs2:14852904-14852904,hs2:14855243-14855243;hs2:15285049-15285049,hs2:15288049-15288049;hs2:40612421-40612421,hs2:40614932-40614932;hs2:43746758-43746758,hs2:204322594-204322594;hs2:44198647-44198647,hs2:191515647-191515647;hs2:44199676-44199676,hs2:198663994-198663994;hs2:45581293-45581293,hs2:180911324-180911324;hs2:45581767-45581767,hs2:184115080-184115080;hs2:45583745-45583745,hs2:198673557-198673557;hs2:45664805-45664805,hs2:45921560-45921560;hs2:45937017-45937017,hs2:155439245-155439245;hs2:48795786-48795786,hs2:49224478-49224478;hs2:49645671-49645671,hs2:202413858-202413858;hs2:50747929-50747929,hs2:58303592-58303592;hs2:50758709-50758709,hs2:180058435-180058435;hs2:50806010-50806010,hs2:65081345-65081345;hs2:51280708-51280708,hs2:51280850-51280850;hs2:51301500-51301500,hs2:154953919-154953919;hs2:57732922-57732922,hs2:57771264-57771264;hs2:57953076-57953076,hs2:180100617-180100617;hs2:58204651-58204651,hs2:58206765-58206765;hs2:58362256-58362256,hs2:155520024-155520024;hs2:58415786-58415786,hs2:174881632-174881632;hs2:71342538-71342538,hs2:71347885-71347885;hs2:75267624-75267624,hs20:29611882-29611882;hs2:75803371-75803371,hs2:75803693-75803693;hs2:77050783-77050783,hs2:77051731-77051731;hs2:77051087-77051087,hs2:77051729-77051729;hs2:80679284-80679284,hs2:80680040-80680040;hs2:118850385-118850385,hs2:118851886-118851886;hs2:130355849-130355849,hs2:130356216-130356216;hs2:133020451-133020451,hs17:45214728-45214728;hs2:133030693-133030693,hsY:10022012-10022012;hs2:133030693-133030693,hs12:38448721-38448721;hs2:136545714-136545714,hs2:157946602-157946602;hs2:136545714-136545714,hs2:166029834-166029834;hs2:136550453-136550453,hs2:136764615-136764615;hs2:136741841-136741841,hs2:146201243-146201243;hs2:145834621-145834621,hs2:157953527-157953527;hs2:145974048-145974048,hs2:200600143-200600143;hs2:145974969-145974969,hs2:184255163-184255163;hs2:145974969-145974969,hs2:198665253-198665253;hs2:145977615-145977615,hs2:184255242-184255242;hs2:146170049-146170049,hs2:199964190-199964190;hs2:146171694-146171694,hs2:158244165-158244165;hs2:146173494-146173494,hs2:198665487-198665487;hs2:146173853-146173853,hs2:188255215-188255215;hs2:146174894-146174894,hs2:184251649-184251649;hs2:152942182-152942182,hs2:175076762-175076762;hs2:154100605-154100605,hs7:45486219-45486219;hs2:154213740-154213740,hs2:191513148-191513148;hs2:154314779-154314779,hs2:154876236-154876236;hs2:154315090-154315090,hs2:201502131-201502131;hs2:154316660-154316660,hs2:184254563-184254563;hs2:154318462-154318462,hs2:185396985-185396985;hs2:154871660-154871660,hs2:180788217-180788217;hs2:154872595-154872595,hs2:201503409-201503409;hs2:154872698-154872698,hs2:154875026-154875026;hs2:154874613-154874613,hs2:186107989-186107989;hs2:155465985-155465985,hs2:155487463-155487463;hs2:157946788-157946788,hs2:166029834-166029834;hs2:158244535-158244535,hs2:184113574-184113574;hs2:158247336-158247336,hs2:188571063-188571063;hs2:158248428-158248428,hs2:187563664-187563664;hs2:160057610-160057610,hs2:166760135-166760135;hs2:166844691-166844691,hs2:171619127-171619127;hs2:174329688-174329688,hs2:180030327-180030327;hs2:174602681-174602681,hs2:174603139-174603139;hs2:174956872-174956872,hs2:199964255-199964255;hs2:174959276-174959276,hs2:180783791-180783791;hs2:174959356-174959356,hs2:188569814-188569814;hs2:175507359-175507359,hs2:175508422-175508422;hs2:180226918-180226918,hs2:180227454-180227454;hs2:180415986-180415986,hs2:180422382-180422382;hs2:180669626-180669626,hs2:195831904-195831904;hs2:180669974-180669974,hs2:195720225-195720225;hs2:180787039-180787039,hs2:186105441-186105441;hs2:180914125-180914125,hs2:200601108-200601108;hs2:183873710-183873710,hs2:184426597-184426597;hs2:184252279-184252279,hs2:184253465-184253465;hs2:184252832-184252832,hs2:184254548-184254548;hs2:184253648-184253648,hs2:200602910-200602910;hs2:184255163-184255163,hs2:186115131-186115131;hs2:184255163-184255163,hs2:198665149-198665149;hs2:185396196-185396196,hs2:199964851-199964851;hs2:186115131-186115131,hs2:198665426-198665426;hs2:187562092-187562092,hs2:188571017-188571017;hs2:187562311-187562311,hs2:188255249-188255249;hs2:188262081-188262081,hs2:198667212-198667212;hs2:189225181-189225181,hs2:189229046-189229046;hs2:191136930-191136930,hs2:201675195-201675195;hs2:195831382-195831382,hs2:196012282-196012282;hs2:196011857-196011857,hs2:196012728-196012728;hs2:198664869-198664869,hs2:200599689-200599689;hs2:201372711-201372711,hs2:202989970-202989970;hs2:205517452-205517452,hs2:205519254-205519254;hs2:223584096-223584096,hs12:105244210-105244210;hs2:228189983-228189983,hs15:93839701-93839701;hs2:228222546-228222546,hs15:93839714-93839714;hs2:229449514-229449514,hs2:229452066-229452066;hs2:230157286-230157286,hs2:230157668-230157668;hs2:240288480-240288480,hs2:240288754-240288754;hs3:303676-303676,hs3:304261-304261;hs3:8390386-8390386,hs22:40515952-40515952;hs3:8390391-8390391,hs22:40516234-40516234;hs3:10190229-10190229,hs3:10191026-10191026;hs3:10226173-10226173,hs3:10228946-10228946;hs3:14132684-14132684,hs3:14133658-14133658;hs3:33003585-33003585,hs3:33008958-33008958;hs3:58534787-58534787,hs3:58537333-58537333;hs3:66054578-66054578,hs3:66055515-66055515;hs3:74147589-74147589,hs3:74154801-74154801;hs3:96050708-96050708,hs3:96051806-96051806;hs3:96132380-96132380,hs3:162848525-162848525;hs3:103922945-103922945,hs3:103925295-103925295;hs3:104791303-104791303,hs3:104792641-104792641;hs3:120161644-120161644,hs3:120164951-120164951;hs3:127529690-127529690,hs3:127530122-127530122;hs3:128672376-128672376,hs3:128675084-128675084;hs3:133235074-133235074,hs3:133235528-133235528;hs3:135697034-135697034,hs3:135701144-135701144;hs3:136515153-136515153,hs3:136517713-136517713;hs3:145479211-145479211,hs3:145479717-145479717;hs3:146427478-146427478,hs3:146428284-146428284;hs3:150202374-150202374,hs3:150203319-150203319;hs3:156929906-156929906,hs5:42974859-42974859;hs3:158732691-158732691,hs3:158734366-158734366;hs3:165362706-165362706,hs3:165363151-165363151;hs3:166054912-166054912,hs3:166056282-166056282;hs3:193135464-193135464,hs3:193142936-193142936;hs3:193720798-193720798,hs3:193726701-193726701;hs4:549027-549027,hs4:549467-549467;hs4:11041506-11041506,hs4:11042659-11042659;hs4:29034054-29034054,hs4:29040404-29040404;hs4:31218703-31218703,hs4:31219432-31219432;hs4:32518403-32518403,hs4:32520077-32520077;hs4:34956601-34956601,hs4:34958180-34958180;hs4:35495333-35495333,hs4:35496897-35496897;hs4:36600070-36600070,hs4:43088243-43088243;hs4:40677281-40677281,hs4:40678298-40678298;hs4:56505801-56505801,hs6:50024388-50024388;hs4:56735154-56735154,hs4:72305540-72305540;hs4:61291652-61291652,hs6:42687772-42687772;hs4:61314477-61314477,hs6:46486136-46486136;hs4:61322424-61322424,hs4:72850763-72850763;hs4:61365098-61365098,hs6:45942061-45942061;hs4:61374146-61374146,hs4:72680416-72680416;hs4:61387363-61387363,hs6:42035105-42035105;hs4:61543180-61543180,hs6:38203449-38203449;hs4:61770620-61770620,hs6:38008158-38008158;hs4:61776497-61776497,hs6:42534094-42534094;hs4:61821373-61821373,hs4:72787536-72787536;hs4:61827372-61827372,hs6:41625082-41625082;hs4:61860512-61860512,hs4:73885155-73885155;hs4:61920367-61920367,hs6:37877201-37877201;hs4:62911757-62911757,hs6:46905154-46905154;hs4:63271077-63271077,hs6:47126719-47126719;hs4:64774590-64774590,hs4:72914994-72914994;hs4:64797563-64797563,hs6:53467881-53467881;hs4:64800108-64800108,hs4:74529066-74529066;hs4:64827432-64827432,hs4:68341722-68341722;hs4:64829174-64829174,hs6:54769132-54769132;hs4:64865378-64865378,hs4:74650480-74650480;hs4:64926029-64926029,hs4:68071848-68071848;hs4:64961354-64961354,hs4:73125644-73125644;hs4:65254066-65254066,hs6:43801661-43801661;hs4:66307976-66307976,hs6:46264801-46264801;hs4:66398309-66398309,hs6:54897764-54897764;hs4:66985257-66985257,hs6:42004908-42004908;hs4:67035949-67035949,hs6:42047962-42047962;hs4:67250283-67250283,hs6:50727212-50727212;hs4:67349757-67349757,hs6:39541854-39541854;hs4:67350161-67350161,hs6:39724025-39724025;hs4:67363420-67363420,hs6:39682788-39682788;hs4:67375635-67375635,hs6:40342285-40342285;hs4:67422366-67422366,hs6:40247057-40247057;hs4:67639272-67639272,hs4:70907495-70907495;hs4:67730940-67730940,hs6:44149197-44149197;hs4:68260167-68260167,hs4:73795257-73795257;hs4:68260852-68260852,hs6:46055495-46055495;hs4:68583433-68583433,hs4:73930334-73930334;hs4:69021123-69021123,hs6:42058157-42058157;hs4:69307833-69307833,hs6:45847411-45847411;hs4:69325966-69325966,hs4:73012607-73012607;hs4:69331654-69331654,hs4:70454397-70454397;hs4:69382721-69382721,hs4:74831950-74831950;hs4:69736878-69736878,hs4:73327798-73327798;hs4:69777210-69777210,hs6:44192602-44192602;hs4:69782971-69782971,hs6:46023440-46023440;hs4:69796714-69796714,hs6:40288704-40288704;hs4:69799579-69799579,hs6:40299958-40299958;hs4:69855761-69855761,hs6:45426848-45426848;hs4:69867267-69867267,hs4:73009343-73009343;hs4:69927481-69927481,hs6:38319491-38319491;hs4:69929129-69929129,hs6:40386640-40386640;hs4:70037180-70037180,hs4:70321094-70321094;hs4:70147887-70147887,hs4:71045840-71045840;hs4:70201180-70201180,hs6:39714969-39714969;hs4:70242616-70242616,hs6:46029342-46029342;hs4:70286335-70286335,hs6:39536537-39536537;hs4:70356653-70356653,hs4:70401523-70401523;hs4:70357933-70357933,hs6:45325759-45325759;hs4:70358183-70358183,hs6:45325215-45325215;hs4:70374860-70374860,hs4:72368690-72368690;hs4:70426107-70426107,hs6:51295062-51295062;hs4:70461621-70461621,hs6:39434325-39434325;hs4:70464610-70464610,hs6:39830957-39830957;hs4:70465475-70465475,hs6:52600030-52600030;hs4:70468193-70468193,hs6:39713660-39713660;hs4:70475755-70475755,hs6:53399467-53399467;hs4:70477445-70477445,hs4:72532139-72532139;hs4:70969237-70969237,hs6:42672500-42672500;hs4:70999037-70999037,hs6:37790414-37790414;hs4:71031750-71031750,hs6:42195265-42195265;hs4:71043413-71043413,hs6:38867743-38867743;hs4:71321475-71321475,hs4:75616176-75616176;hs4:71760538-71760538,hs6:52468096-52468096;hs4:72221435-72221435,hs4:74913127-74913127;hs4:72346521-72346521,hs6:38001492-38001492;hs4:72394537-72394537,hs6:44349873-44349873;hs4:72508937-72508937,hs6:52515067-52515067;hs4:72531545-72531545,hs4:75328317-75328317;hs4:72539000-72539000,hs4:73850843-73850843;hs4:72540287-72540287,hs4:73407110-73407110;hs4:72678368-72678368,hs6:46471924-46471924;hs4:72687561-72687561,hs6:51378820-51378820;hs4:72783347-72783347,hs6:50781613-50781613;hs4:72822856-72822856,hs4:73204772-73204772;hs4:72868477-72868477,hs6:37889745-37889745;hs4:72886024-72886024,hs6:52227693-52227693;hs4:73022937-73022937,hs6:45564359-45564359;hs4:73090679-73090679,hs6:37462877-37462877;hs4:73093019-73093019,hs6:37186575-37186575;hs4:73123300-73123300,hs4:74784717-74784717;hs4:73125983-73125983,hs6:45865830-45865830;hs4:73147145-73147145,hs6:42535198-42535198;hs4:73237228-73237228,hs6:40490401-40490401;hs4:73276316-73276316,hs4:74564039-74564039;hs4:73317195-73317195,hs6:38391083-38391083;hs4:73590363-73590363,hs4:73850353-73850353;hs4:73672439-73672439,hs6:37992960-37992960;hs4:73678830-73678830,hs6:47850223-47850223;hs4:73688938-73688938,hs6:38162362-38162362;hs4:73781107-73781107,hs6:52605399-52605399;hs4:73793180-73793180,hs6:42917329-42917329;hs4:73798560-73798560,hs6:50023699-50023699;hs4:73851426-73851426,hs6:44094033-44094033;hs4:74047626-74047626,hs4:74573827-74573827;hs4:74452238-74452238,hs6:46230005-46230005;hs4:74473358-74473358,hs6:37893966-37893966;hs4:74562597-74562597,hs4:74568092-74568092;hs4:74757196-74757196,hs6:46519016-46519016;hs4:74772992-74772992,hs6:48016925-48016925;hs4:74885295-74885295,hs6:41776179-41776179;hs4:75133655-75133655,hs6:49674164-49674164;hs4:75338842-75338842,hs6:45341568-45341568;hs4:75495549-75495549,hs6:38312416-38312416;hs4:75503289-75503289,hs6:39549060-39549060;hs4:75514221-75514221,hs6:40360626-40360626;hs4:75532619-75532619,hs6:39712955-39712955;hs4:75545651-75545651,hs6:39579273-39579273;hs4:75546403-75546403,hs6:40513134-40513134;hs4:75723349-75723349,hs6:38634767-38634767;hs4:75796465-75796465,hs6:37013151-37013151;hs4:80894548-80894548,hs5:51922582-51922582;hs4:95637744-95637744,hs4:95638665-95638665;hs4:110294606-110294606,hs9:128679225-128679225;hs4:110294615-110294615,hs9:128679304-128679304;hs4:112297323-112297323,hs4:112309618-112309618;hs4:120963567-120963567,hs4:120965123-120965123;hs4:130280832-130280832,hs4:130282938-130282938;hs4:132490414-132490414,hs4:132493639-132493639;hs4:155267664-155267664,hs4:155270456-155270456;hs4:179240638-179240638,hs4:179246433-179246433;hs4:179772405-179772405,hs4:179773729-179773729;hs4:187843681-187843681,hs4:187850410-187850410;hs4:190381898-190381898,hs4:190382468-190382468;hs5:16150014-16150014,hs5:16150781-16150781;hs5:28216660-28216660,hs5:28225302-28225302;hs5:32085341-32085341,hs5:32085836-32085836;hs5:33111866-33111866,hs5:33112668-33112668;hs5:40115029-40115029,hs5:40115347-40115347;hs5:62168532-62168532,hs5:62169406-62169406;hs5:62168542-62168542,hs5:62169251-62169251;hs5:65241576-65241576,hs5:65242944-65242944;hs5:83756705-83756705,hs5:83787400-83787400;hs5:89003720-89003720,hs5:89004043-89004043;hs5:98477590-98477590,hs5:98478333-98478333;hs5:109297106-109297106,hs5:109297424-109297424;hs5:120649513-120649513,hs5:120652351-120652351;hs5:121294717-121294717,hs5:121295024-121295024;hs5:146781914-146781914,hs5:146782225-146782225;hs5:147338021-147338021,hs5:147340539-147340539;hs5:157333021-157333021,hs5:157334789-157334789;hs5:161066845-161066845,hs5:161070868-161070868;hs6:862024-862024,hs6:863770-863770;hs6:9789584-9789584,hs6:9789929-9789929;hs6:12617335-12617335,hs6:12617658-12617658;hs6:29405334-29405334,hs6:29406264-29406264;hs6:30750567-30750567,hs6:30760312-30760312;hs6:37144599-37144599,hs17:68436545-68436545;hs6:37296784-37296784,hs6:45672501-45672501;hs6:37330001-37330001,hs6:37584068-37584068;hs6:37582271-37582271,hs6:42172945-42172945;hs6:37582576-37582576,hs6:42374789-42374789;hs6:37584534-37584534,hs6:41332958-41332958;hs6:37584534-37584534,hs6:43930404-43930404;hs6:38034841-38034841,hs6:40859348-40859348;hs6:38153369-38153369,hs6:45940627-45940627;hs6:38153373-38153373,hs6:50825226-50825226;hs6:38153950-38153950,hs6:38157545-38157545;hs6:38155775-38155775,hs6:38158203-38158203;hs6:38353777-38353777,hs6:40500512-40500512;hs6:38359233-38359233,hs6:44187553-44187553;hs6:38390796-38390796,hs6:40353873-40353873;hs6:38443917-38443917,hs6:39738091-39738091;hs6:38458070-38458070,hs6:46055394-46055394;hs6:38459820-38459820,hs6:39683778-39683778;hs6:38546919-38546919,hs6:42010242-42010242;hs6:38666911-38666911,hs6:44905744-44905744;hs6:39144640-39144640,hs6:39337875-39337875;hs6:39421988-39421988,hs6:46031527-46031527;hs6:39430148-39430148,hs6:39718787-39718787;hs6:39524116-39524116,hs6:45315045-45315045;hs6:39524614-39524614,hs6:40490741-40490741;hs6:39534810-39534810,hs6:40302311-40302311;hs6:39551790-39551790,hs6:39718805-39718805;hs6:39559911-39559911,hs6:46006453-46006453;hs6:39561873-39561873,hs6:40386062-40386062;hs6:39590633-39590633,hs6:40379921-40379921;hs6:39597186-39597186,hs6:40381706-40381706;hs6:39603801-39603801,hs6:40300514-40300514;hs6:39824878-39824878,hs6:39830195-39830195;hs6:39830972-39830972,hs6:45313480-45313480;hs6:40301467-40301467,hs6:45892832-45892832;hs6:40357236-40357236,hs6:44201753-44201753;hs6:40434170-40434170,hs6:40436433-40436433;hs6:40486703-40486703,hs6:45800614-45800614;hs6:42041978-42041978,hs6:46098560-46098560;hs6:42172757-42172757,hs6:42374619-42374619;hs6:42374029-42374029,hs6:42374342-42374342;hs6:43966019-43966019,hs6:45803485-45803485;hs6:44097579-44097579,hs6:46511569-46511569;hs6:44098924-44098924,hs6:44099205-44099205;hs6:44415932-44415932,hs6:47704999-47704999;hs6:45300645-45300645,hs6:45594959-45594959;hs6:45352304-45352304,hs6:45834408-45834408;hs6:45569528-45569528,hs6:45784499-45784499;hs6:45656518-45656518,hs6:45803035-45803035;hs6:45809737-45809737,hs6:50828074-50828074;hs6:45891533-45891533,hs6:46024138-46024138;hs6:46228944-46228944,hs6:46229443-46229443;hs6:46516653-46516653,hs6:52673426-52673426;hs6:46541475-46541475,hs6:53089412-53089412;hs6:46542199-46542199,hs6:47847426-47847426;hs6:46542199-46542199,hs6:47849278-47849278;hs6:46921151-46921151,hs6:52022842-52022842;hs6:47814214-47814214,hs6:53101248-53101248;hs6:47847298-47847298,hs6:51057787-51057787;hs6:47847305-47847305,hs6:47849279-47849279;hs6:47849117-47849117,hs6:51058283-51058283;hs6:48018906-48018906,hs6:50846206-50846206;hs6:48079946-48079946,hs6:50287743-50287743;hs6:50006325-50006325,hs6:50007302-50007302;hs6:50039728-50039728,hs6:50724263-50724263;hs6:51008834-51008834,hs6:51058251-51058251;hs6:51451682-51451682,hs6:51452716-51452716;hs6:52300534-52300534,hs6:53412938-53412938;hs6:69242132-69242132,hs6:69242467-69242467;hs6:74868419-74868419,hs6:74869551-74869551;hs6:78474929-78474929,hs6:78475539-78475539;hs6:87108996-87108996,hs6:87113979-87113979;hs6:88801144-88801144,hs6:88802418-88802418;hs6:96700327-96700327,hs6:96701491-96701491;hs6:121512131-121512131,hs6:121525981-121525981;hs6:121512690-121512690,hs6:121519182-121519182;hs6:121548091-121548091,hs16:88766764-88766764;hs6:121548093-121548093,hs16:88766445-88766445;hs6:126238342-126238342,hs20:34417751-34417751;hs6:134062939-134062939,hs6:134063418-134063418;hs6:142817874-142817874,hs15:96435347-96435347;hs6:143536183-143536183,hs6:143537295-143537295;hs6:161215590-161215590,hs6:161218696-161218696;hs6:163693928-163693928,hs6:163694238-163694238;hs6:164267870-164267870,hs6:164268641-164268641;hs6:166497640-166497640,hs6:166502589-166502589;hs7:297897-297897,hs7:298510-298510;hs7:4416558-4416558,hs7:4420180-4420180;hs7:14918489-14918489,hs7:14919016-14919016;hs7:26305770-26305770,hs7:26308106-26308106;hs7:34278370-34278370,hs7:34281622-34281622;hs7:37186589-37186589,hs7:37187528-37187528;hs7:46829823-46829823,hs7:46832394-46832394;hs7:52275101-52275101,hs7:52275692-52275692;hs7:75335794-75335794,hs7:75337477-75337477;hs7:75668028-75668028,hs7:75668678-75668678;hs7:79471620-79471620,hs7:79481677-79481677;hs7:88914961-88914961,hs7:88915195-88915195;hs7:88953438-88953438,hs7:88954106-88954106;hs7:91562310-91562310,hs7:91564686-91564686;hs7:98228545-98228545,hs7:98230753-98230753;hs7:100337906-100337906,hs7:100340529-100340529;hs7:100894510-100894510,hs7:100895088-100895088;hs7:112774314-112774314,hs7:112776378-112776378;hs7:112774319-112774319,hs7:112775630-112775630;hs7:119387203-119387203,hs7:119388643-119388643;hs7:124634581-124634581,hs7:124637722-124637722;hs7:125525708-125525708,hs7:125526357-125526357;hs7:146253830-146253830,hs7:146254805-146254805;hs7:146299967-146299967,hs7:146302642-146302642;hs7:148566290-148566290,hs7:148566882-148566882;hs7:152360244-152360244,hs7:152360735-152360735;hs7:154885249-154885249,hs7:154889497-154889497;hs8:1938512-1938512,hs8:1939301-1939301;hs8:4475981-4475981,hs8:4486265-4486265;hs8:8760608-8760608,hs8:8761582-8761582;hs8:14945529-14945529,hsX:124433950-124433950;hs8:14946079-14946079,hsX:124433939-124433939;hs8:24593553-24593553,hs8:24595565-24595565;hs8:53185078-53185078,hs8:53187087-53187087;hs8:56998106-56998106,hs8:57000090-57000090;hs8:60996551-60996551,hs8:61007776-61007776;hs8:62512859-62512859,hs8:62515432-62515432;hs8:69488483-69488483,hs8:69488906-69488906;hs8:108781412-108781412,hs8:108782421-108782421;hs8:127401175-127401175,hs8:127404943-127404943;hs8:128946862-128946862,hs8:128948039-128948039;hs8:130141031-130141031,hs8:130145148-130145148;hs8:130435195-130435195,hs8:130442878-130442878;hs8:136218380-136218380,hs8:136220121-136220121;hs8:139910365-139910365,hs8:139919651-139919651;hs8:142502481-142502481,hs8:142503301-142503301;hs9:4397106-4397106,hs9:4398768-4398768;hs9:13655422-13655422,hs9:13655754-13655754;hs9:22666441-22666441,hs9:22666932-22666932;hs9:26275787-26275787,hs9:26306271-26306271;hs9:27619443-27619443,hs9:27624788-27624788;hs9:30908193-30908193,hs9:30909483-30909483;hs9:34596852-34596852,hs9:34599790-34599790;hs9:66455691-66455691,hs9:68414096-68414096;hs9:72298245-72298245,hs9:72298727-72298727;hs9:90065583-90065583,hs9:90066374-90066374;hs9:99395970-99395970,hs9:99396788-99396788;hs9:109774677-109774677,hs9:109775338-109775338;hs9:109775332-109775332,hs20:29878632-29878632;hs9:137138730-137138730,hs9:137140501-137140501;hs10:1037630-1037630,hs10:1037950-1037950;hs10:1110818-1110818,hs10:1117890-1117890;hs10:3226866-3226866,hs10:3228375-3228375;hs10:3574228-3574228,hs10:3575399-3575399;hs10:4437701-4437701,hs10:4441391-4441391;hs10:22151634-22151634,hs10:22161275-22161275;hs10:24569733-24569733,hs10:24570980-24570980;hs10:28564607-28564607,hs10:28572715-28572715;hs10:37816563-37816563,hs10:37823511-37823511;hs10:47088380-47088380,hs10:47088708-47088708;hs10:47088385-47088385,hs10:47088713-47088713;hs10:54929092-54929092,hs10:54938114-54938114;hs10:66131755-66131755,hs10:66132075-66132075;hs10:67342574-67342574,hs10:67344175-67344175;hs10:68241221-68241221,hs10:68241530-68241530;hs10:75123881-75123881,hs10:75128002-75128002;hs10:75373810-75373810,hs10:75381208-75381208;hs10:87242581-87242581,hs10:87243052-87243052;hs10:87243054-87243054,hs10:87245473-87245473;hs10:88321447-88321447,hs10:88326416-88326416;hs10:91998542-91998542,hs10:92002034-92002034;hs11:3767491-3767491,hs11:3768135-3768135;hs11:5445818-5445818,hs11:5548280-5548280;hs11:17209756-17209756,hs11:17211219-17211219;hs11:19555255-19555255,hs11:19555567-19555567;hs11:32611038-32611038,hs11:32617101-32617101;hs11:36137941-36137941,hs11:36140441-36140441;hs11:36138248-36138248,hs11:36141062-36141062;hs11:47875291-47875291,hs11:47877063-47877063;hs11:77254364-77254364,hs11:77256076-77256076;hs11:79972711-79972711,hs11:79983299-79983299;hs11:98473657-98473657,hs11:98476469-98476469;hs11:101565793-101565793,hs11:101575264-101575264;hs11:104923349-104923349,hs11:104931393-104931393;hs11:105293472-105293472,hs11:105298908-105298908;hs11:116712479-116712479,hs11:116712792-116712792;hs11:116863032-116863032,hs11:116863980-116863980;hs11:117406950-117406950,hs11:117467921-117467921;hs11:118549802-118549802,hs11:118562704-118562704;hs11:118913261-118913261,hs11:118913814-118913814;hs11:122788584-122788584,hs11:122789634-122789634;hs11:125286190-125286190,hs11:125290413-125290413;hs12:11113782-11113782,hs12:11114213-11114213;hs12:31112835-31112835,hs12:31115221-31115221;hs12:34207414-34207414,hs12:34216819-34216819;hs12:46631161-46631161,hs12:46632074-46632074;hs12:53596010-53596010,hs12:53596612-53596612;hs12:54074834-54074834,hs12:54076792-54076792;hs12:58509630-58509630,hs12:58513745-58513745;hs12:61243934-61243934,hs14:67419772-67419772;hs12:61244147-61244147,hs14:67418670-67418670;hs12:65017557-65017557,hs12:65018573-65018573;hs12:66791981-66791981,hs12:66794137-66794137;hs12:71886564-71886564,hs12:71889653-71889653;hs12:75111577-75111577,hs12:75115472-75115472;hs12:77721579-77721579,hs12:77722664-77722664;hs12:77721579-77721579,hs12:77722673-77722673;hs12:77722580-77722580,hs12:77722676-77722676;hs12:82592006-82592006,hs12:82592435-82592435;hs12:91241838-91241838,hs12:91244689-91244689;hs12:93210557-93210557,hs12:93211081-93211081;hs12:94339462-94339462,hs12:94342188-94342188;hs12:94339470-94339470,hs12:94342979-94342979;hs12:99016642-99016642,hs12:99017963-99017963;hs12:104278729-104278729,hs12:104278866-104278866;hs12:120355595-120355595,hs12:120357814-120357814;hs12:122081117-122081117,hs12:122082881-122082881;hs12:125642791-125642791,hs12:125653190-125653190;hs12:127404669-127404669,hs12:127406361-127406361;hs12:131059522-131059522,hs12:131059778-131059778;hs13:20547869-20547869,hs13:21948310-21948310;hs13:20547874-20547874,hs13:34850286-34850286;hs13:21948311-21948311,hs13:34850280-34850280;hs13:23325564-23325564,hs13:23327245-23327245;hs13:26449367-26449367,hs13:26449881-26449881;hs13:28693969-28693969,hs13:28697346-28697346;hs13:59227263-59227263,hs13:59235010-59235010;hs13:69699229-69699229,hs13:69699711-69699711;hs13:78593665-78593665,hs13:78596744-78596744;hs13:86673794-86673794,hs13:86676248-86676248;hs13:113263314-113263314,hs13:113267875-113267875;hs13:113325158-113325158,hs13:113326356-113326356;hs14:33941744-33941744,hs14:33942278-33942278;hs14:44980277-44980277,hs17:41464006-41464006;hs14:52756791-52756791,hs14:52757122-52757122;hs14:62654062-62654062,hs14:62665105-62665105;hs14:76313064-76313064,hs14:76314916-76314916;hs14:87555901-87555901,hs14:87556222-87556222;hs14:102876625-102876625,hs14:102878085-102878085;hs15:25107032-25107032,hs15:25109421-25109421;hs15:25833657-25833657,hs15:25835386-25835386;hs15:27213445-27213445,hs15:27213771-27213771;hs15:45316348-45316348,hs15:45319338-45319338;hs15:46254965-46254965,hs15:46257494-46257494;hs15:48260723-48260723,hs15:48266515-48266515;hs15:51978919-51978919,hs15:51986664-51986664;hs15:51978928-51978928,hs15:51986537-51986537;hs15:85479382-85479382,hs15:85479683-85479683;hs15:89483962-89483962,hs15:89486551-89486551;hs15:99711868-99711868,hs15:99712323-99712323;hs16:296533-296533,hs16:300059-300059;hs16:9250190-9250190,hs16:9250787-9250787;hs16:11866055-11866055,hs16:11867743-11867743;hs16:26916920-26916920,hs16:26919504-26919504;hs16:31921481-31921481,hs16:31924268-31924268;hs16:33952595-33952595,hs16:33956031-33956031;hs16:34336815-34336815,hs16:34337356-34337356;hs16:52147348-52147348,hs16:52150631-52150631;hs16:57810326-57810326,hs21:39130447-39130447;hs16:57810650-57810650,hs21:39130453-39130453;hs16:59468927-59468927,hs16:59471506-59471506;hs16:60466727-60466727,hs16:60467430-60467430;hs16:68617354-68617354,hs16:68623421-68623421;hs16:73613666-73613666,hs16:73687835-73687835;hs16:73616832-73616832,hs16:73687535-73687535;hs16:76598920-76598920,hs16:76601564-76601564;hs16:79059786-79059786,hs16:79063002-79063002;hs16:89015953-89015953,hs16:89016402-89016402;hs17:2145674-2145674,hs17:2146011-2146011;hs17:5277498-5277498,hs17:5278070-5278070;hs17:7524434-7524434,hs17:7524942-7524942;hs17:17234334-17234334,hs17:17235372-17235372;hs17:26782412-26782412,hs17:26783510-26783510;hs17:37480258-37480258,hs17:37480784-37480784;hs17:39189734-39189734,hs17:39195213-39195213;hs17:40602532-40602532,hs17:40604066-40604066;hs17:46159882-46159882,hs17:46162290-46162290;hs17:58579854-58579854,hs17:58581278-58581278;hs17:74279957-74279957,hs17:74280899-74280899;hs17:77992016-77992016,hs17:78000845-78000845;hs17:80651978-80651978,hs17:80653608-80653608;hs18:108890-108890,hs18:111145-111145;hs18:108983-108983,hsY:58997380-58997380;hs18:109440-109440,hsY:13485461-13485461;hs18:109519-109519,hsY:13486055-13486055;hs18:110932-110932,hsY:13468034-13468034;hs18:110932-110932,hsY:13484731-13484731;hs18:111069-111069,hsY:13482129-13482129;hs18:111592-111592,hsY:13490058-13490058;hs18:111627-111627,hsY:13464601-13464601;hs18:2119004-2119004,hs18:2120007-2120007;hs18:3322533-3322533,hs18:3323390-3323390;hs18:25974129-25974129,hs18:25981537-25981537;hs18:57546764-57546764,hs18:57547709-57547709;hs18:62041804-62041804,hs18:62042485-62042485;hs18:63635466-63635466,hs18:63640220-63640220;hs18:63829979-63829979,hs18:63834929-63834929;hs18:64006981-64006981,hs18:64008005-64008005;hs18:70766665-70766665,hs18:70769265-70769265;hs18:76542043-76542043,hs18:76543042-76543042;hs18:77679690-77679690,hs18:77681892-77681892;hs19:2131437-2131437,hs19:2131884-2131884;hs19:2820731-2820731,hs19:2821733-2821733;hs19:9863578-9863578,hs19:9871837-9871837;hs19:13479570-13479570,hs19:13479890-13479890;hs19:16042429-16042429,hs19:16044869-16044869;hs19:16814869-16814869,hs19:16816460-16816460;hs19:22423045-22423045,hs19:22426404-22426404;hs19:32703649-32703649,hs19:32704486-32704486;hs19:45473179-45473179,hs19:45474322-45474322;hs19:49072332-49072332,hs19:49075504-49075504;hs19:50554802-50554802,hs19:50561432-50561432;hs19:54180255-54180255,hs19:54181478-54181478;hs19:56211483-56211483,hs19:56211948-56211948;hs19:57202816-57202816,hs19:57212270-57212270;hs20:565737-565737,hs20:566302-566302;hs20:3084985-3084985,hs20:3085579-3085579;hs20:4012510-4012510,hs20:4016482-4016482;hs20:4445321-4445321,hs20:4449530-4449530;hs20:5702592-5702592,hs20:5704784-5704784;hs20:7600868-7600868,hs20:7605002-7605002;hs20:7601036-7601036,hs20:7607572-7607572;hs20:7605002-7605002,hs20:7607569-7607569;hs20:14980987-14980987,hs20:14981318-14981318;hs20:23168343-23168343,hs20:23176317-23176317;hs20:24249643-24249643,hs20:24250475-24250475;hs20:52331746-52331746,hs20:52336663-52336663;hs20:61372626-61372626,hs20:61374774-61374774;hs21:9825604-9825604,hsY:10034199-10034199;hs21:23188329-23188329,hs21:23202329-23202329;hs21:24423331-24423331,hs21:24435107-24435107;hs21:25286457-25286457,hs21:25286765-25286765;hs21:31639129-31639129,hs21:31644641-31644641;hs21:43703855-43703855,hs21:43704401-43704401;hs22:19558040-19558040,hs22:19558431-19558431;hs22:24876431-24876431,hs22:24877008-24877008;hs22:29679476-29679476,hs22:29681965-29681965;hs22:36943236-36943236,hs22:36949761-36949761;hs22:37438442-37438442,hs22:37438952-37438952;hs22:37983487-37983487,hs22:37984458-37984458;hs22:40307364-40307364,hs22:40311283-40311283;hs22:41294233-41294233,hs22:41294566-41294566;hs22:41591135-41591135,hs22:41592350-41592350;hs22:44564946-44564946,hs22:44566028-44566028;hs22:45554720-45554720,hs22:45557125-45557125;hs22:50975831-50975831,hs22:50976607-50976607;hsX:166633-166633,hsX:167725-167725;hsX:329022-329022,hsX:329652-329652;hsX:463256-463256,hsX:463654-463654;hsX:550811-550811,hsX:551367-551367;hsX:1715483-1715483,hsX:1715831-1715831;hsX:4233775-4233775,hsX:4234934-4234934;hsX:24756048-24756048,hsX:24756378-24756378;hsX:27963119-27963119,hsX:27963465-27963465;hsX:35714098-35714098,hsX:35716003-35716003;hsX:42332640-42332640,hsX:42334340-42334340;hsX:105807021-105807021,hsX:105807807-105807807;hsX:113319219-113319219,hsX:113323147-113323147;hsX:125941758-125941758,hsX:125943168-125943168;hsX:133394263-133394263,hsX:133397232-133397232;hsX:138122585-138122585,hsX:138130730-138130730;hsX:149278738-149278738,hsX:149279189-149279189;hsY:13467541-13467541,hsY:13485459-13485459;hsY:13481777-13481777,hsY:13485461-13485461;hsY:13482150-13482150,hsY:58997379-58997379;hsY:13485408-13485408,hsY:13485953-13485953;hsY:13485463-13485463,hsY:58995275-58995275;hsY:58986969-58986969,hsY:58996191-58996191 ACSL3;ALLC;ALS2CR11;ANKRD30BL;AOX1;AOX2P;ARL6IP6;BOLL;BZW1;C11orf63;C14orf28;C16orf72;C16orf82;C20orf196;C3orf58;C4orf32;C4orf33;C5orf46;C6orf118;C6orf132;C6orf223;C8orf34;C9orf170;C9orf72;CACNB4;CALCRL;CCDC85A;CDCA7;CSN1S2BP;CTNNA2;CWC22;CXCR4;CXorf57;CYTIP;DARS;DKFZp686O1327;DNER;ERMN;EVA1A;FAM171B;FAM84A;FANCL;Feb-07;FLJ35282;FONG;FSHR;FSIP2;GALNT13;GALNT5;GNN;GPD2;GPR39;GULP1;HDAC4;HIBCH;HS6ST1;INSIG2;KCNJ3;KCTD18;LCT;LOC100130581;LOC100132354;LOC100144602;LOC100272228;LOC100287639;LOC100505619;LOC100505695;LOC100505964;LOC100506172;LOC100506714;LOC100652824;LOC145820;LOC150185;LOC285501;LOC286094;LOC338758;LOC339535;LOC401164;LOC401397;LOC401497;LOC642236;LOC643401;LOC644649;LOC728724;LRPPRC;LRRTM4;MBD5;MCEE;MFF;MIR302F;MIR4275;MOGAT1;MRPL19;NAB1;NBAS;NCKAP1;NRXN1;NUP35;OLA1;PABPC1P2;PARD3B;PID1;PLCL1;POLE4;PRKCE;RAPH1;RPRM;SATB2;SATB2-AS1;SCN1A;SCN3A;SERTAD2;SESTD1;SLC39A10;SLC8A1;SNTG2;SP3;SP5;SPHKAP;SRBD1;STON1;STON1-GTF2A1L;TACR1;TANC1;TFPI;THADA;TPO;TTC21B;UBE2E3;UNQ6975;VRK2;WIPF1;ZNF385B;ZNF804A; Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Nuffield Department of Clinical Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK Papillary renal cell carcinoma (pRCC) is an important subtype of kidney cancer with a problematic pathological classification and highly variable clinical behaviour. Here we sequence the genomes or exomes of 31 pRCCs, and in four tumours, multi-region sequencing is undertaken. We identify BAP1, SETD2, ARID2 and Nrf2 pathway genes (KEAP1, NHE2L2 and CUL3) as probable drivers, together with at least eight other possible drivers. However, only ~10% of tumours harbour detectable pathogenic changes in any one driver gene, and where present, the mutations are often predicted to be present within cancer sub-clones. We specifically detect parallel evolution of multiple SETD2 mutations within different sub-regions of the same tumour. By contrast, large copy number gains of chromosomes 7, 12, 16 and 17 are usually early, monoclonal changes in pRCC evolution. The predominance of large copy number variants as the major drivers for pRCC highlights an unusual mode of tumorigenesis that may challenge precision medicine approaches. GRCh37/hg19 PRJEB7875;ERP008861 Yes NA CTDB0379 Research 24703847 Chen X, Bahrami A, Pappo A, Easton J, Dalton J, Hedlund E, Ellison D, Shurtleff S, Wu G, Wei L, Parker M, Rusch M, Nagahawatte P, Wu J, Mao S, Boggs K, Mulder H, Yergeau D, Lu C, Ding L, Edmonson M, Qu C, Wang J, Li Y, Navid F, Daw NC, Mardis ER, Wilson RK, Downing JR, Zhang J, Dyer MA Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma Cell Reports 2014 Apr 14 Osteosarcoma Next Generation Sequencing Homo sapiens SJOS002_D Illumina HiSeq2000 chr10:0-135534747:0;chr11:0-71613771:0;chr11:103889008-121575185:-1;chr11:103952154-103253501:1;chr11:122176328-131408959:0;chr11:131213451-135006516:0;chr11:131408960-76092707:1;chr11:132648731-131213450:1;chr11:71613772-122176327:-1;chr11:76092708-132648730:0;chr11:90246731-120596801:-1;chr11:95512737-101280774:-1;chr11:98420694-120996374:-1;chr11:98440720-96986497:1;chr12:0-58692187:0;chr12:120744076-27442273:1;chr12:27442274-133851895:0;chr12:58692188-58955480:-1;chr12:58769898-58769574:1;chr12:58775894-59702388:-1;chr12:58957116-58915309:1;chr12:59092557-75937349:-1;chr12:59702560-58776610:1;chr12:59811459-59806283:1;chr12:60307738-68233914:-1;chr12:60326005-60573018:-1;chr12:60483029-70880352:-1;chr12:60573878-68233119:-1;chr12:60573902-68233119:-1;chr12:61886844-67452370:-1;chr12:62260868-120744075:0;chr12:62262292-58095289:1;chr12:63072135-79798646:0;chr12:63186042-69025304:-1;chr12:64011768-64011513:1;chr12:64671384-75447089:-1;chr12:65377452-58173036:1;chr12:65388046-76214942:-1;chr12:65411562-65325515:1;chr12:67948152-67971521:-1;chr12:68225780-58061093:1;chr12:68232099-62995752:1;chr12:68234373-60577402:1;chr12:68450503-75560099:-1;chr12:68574651-75537713:-1;chr12:69123645-57941843:1;chr12:69328648-62261792:1;chr12:69348040-62996464:1;chr12:69394467-57940344:1;chr12:69515813-58888761:1;chr12:69535848-76206682:-1;chr12:72534415-84050222:0;chr12:75297354-65441697:1;chr12:75522769-68516366:1;chr12:76214943-77965620:0;chr12:77965621-63072134:1;chr12:79798647-72534414:1;chr12:84050223-62260867:1;chr13:0-46029610:0;chr13:46029611-46029827:-1;chr13:46029828-60637849:0;chr13:60637850-60905564:-1;chr13:60905565-74405539:0;chr13:74405540-74442657:-1;chr13:74408932-74435322:-1;chr13:74436326-74404322:1;chr13:74442658-74443039:0;chr13:74442673-74443440:0;chr13:74443040-74442672:1;chr13:74443441-74472827:-1;chr13:74445875-74442649:1;chr13:74450392-74404726:1;chr13:74457710-74454523:1;chr13:74472828-115169878:0;chr14:0-37704867:0;chr14:104640279-104807809:-1;chr14:106047534-95219410:1;chr14:106047632-106119737:0;chr14:106119738-95189489:1;chr14:37704868-37756329:-1;chr14:37756330-38256873:0;chr14:38256874-52276329:-1;chr14:52276330-57567834:0;chr14:57567835-59613843:-1;chr14:59613844-94498157:0;chr14:83152541-95219400:0;chr14:94498158-83152540:1;chr14:95189490-107349540:0;chr14:95219401-106047631:-1;chr15:0-45047577:0;chr15:45047578-95705115:-1;chr15:95705116-102531392:0;chr16:0-12093954:0;chr16:12093955-27841896:-1;chr16:17294995-9986441:1;chr16:27841897-90354753:0;chr17:0-738923:0;chr17:18593076-18593411:-1;chr17:18593412-60794805:0;chr17:60660819-81195210:0;chr17:60794806-60660818:1;chr17:738924-739325:-1;chr17:739326-18593075:0;chr18:0-34043981:0;chr18:34021094-44665793:0;chr18:34043982-34021093:1;chr18:44665794-59948284:-1;chr18:57470679-55260330:1;chr18:59948285-78077248:0;chr19:0-59128983:0;chr1:0-1767241:0;chr1:12921813-16645481:-1;chr1:13183046-62892392:-1;chr1:17052280-8812098:1;chr1:1767242-4131638:-1;chr1:19351410-61357865:-1;chr1:4131639-4902503:0;chr1:4902504-14543022:-1;chr1:5246760-5246991:-1;chr1:5261668-73907295:0;chr1:5577993-63503493:-1;chr1:61661531-64000323:0;chr1:62454541-63953956:0;chr1:62455781-6921552:1;chr1:63503494-63557898:0;chr1:63557899-62454540:1;chr1:63953957-61661530:1;chr1:64000324-7481569:1;chr1:67891191-249250621:0;chr1:6913766-14405593:-1;chr1:71641756-5261667:1;chr1:73907296-67891190:1;chr1:7481570-71641755:0;chr20:0-14771942:0;chr20:14771943-14872416:-1;chr20:14872417-53048666:0;chr20:32950160-63025520:0;chr20:53048667-32950159:1;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-947434:0;chr2:116067900-203351950:0;chr2:118835673-133209500:0;chr2:126784476-127241559:0;chr2:127241560-127379646:-1;chr2:127379647-127761459:0;chr2:127761460-118835672:1;chr2:133209501-134682002:-1;chr2:134682003-136542262:0;chr2:136542263-116067899:1;chr2:1637698-27591527:-1;chr2:203351951-204324074:-1;chr2:204324075-234699147:0;chr2:22018802-24357370:-1;chr2:234699148-234699289:-1;chr2:234699290-243199373:0;chr2:24321715-44531720:-1;chr2:24337787-51977808:-1;chr2:27573056-1638810:1;chr2:27653615-46067240:-1;chr2:3758192-1632550:1;chr2:44531331-44631182:-1;chr2:44635104-46101149:-1;chr2:45044544-43164903:1;chr2:45429957-48659054:-1;chr2:45430509-74752572:0;chr2:48754853-7382996:1;chr2:51977809-52935046:0;chr2:52935047-6230834:1;chr2:57833159-6392985:1;chr2:57834664-6405821:1;chr2:57855104-45430508:1;chr2:6230835-57833158:0;chr2:6329662-4853381:1;chr2:6392986-57834663:0;chr2:6398793-6412414:-1;chr2:6405822-57855103:0;chr2:6408841-7382866:-1;chr2:7381416-7868142:-1;chr2:74752573-75653056:-1;chr2:75653057-81420483:0;chr2:81420484-85444719:-1;chr2:83664071-126784475:-1;chr2:85003866-84649371:1;chr2:85054695-86870615:-1;chr2:85443998-81406246:1;chr2:85508477-85423571:1;chr2:85511647-85229540:1;chr2:85824365-85826341:-1;chr2:86162759-74790864:1;chr2:947435-24303566:-1;chr3:0-174028:0;chr3:116046858-117092131:-1;chr3:116267412-116973526:-1;chr3:117092132-134628897:0;chr3:134628898-137795525:-1;chr3:137775801-137767529:1;chr3:137795526-138352632:0;chr3:138352633-89159729:1;chr3:138466470-158477274:-1;chr3:140936642-140955085:-1;chr3:147525461-147543381:-1;chr3:147556578-147556136:1;chr3:148716158-149859188:-1;chr3:149812607-149805615:1;chr3:151356858-158095895:-1;chr3:151462707-157254835:-1;chr3:153012441-160774600:0;chr3:156915637-58449251:1;chr3:157418972-137784124:1;chr3:158368704-89160005:1;chr3:158477275-158933707:0;chr3:158933708-153012440:1;chr3:159165021-167038468:0;chr3:160774601-159165020:1;chr3:167038469-167043390:-1;chr3:167043359-167530050:-1;chr3:167530051-198022430:0;chr3:174029-579561:-1;chr3:2152777-2196027:0;chr3:2196028-3011887:-1;chr3:2817325-1936654:1;chr3:3011888-58448830:0;chr3:407444-2152776:-1;chr3:580575-2136225:-1;chr3:58448831-90175330:-1;chr3:66157118-61876348:1;chr3:66274621-62107074:1;chr3:66278360-66277907:1;chr3:89159730-138466469:0;chr3:90036829-90036377:1;chr3:90175331-116046857:0;chr4:0-59808971:0;chr4:59808972-59809024:-1;chr4:59809025-191154276:0;chr5:0-96617964:0;chr5:96617965-96618058:-1;chr5:96618059-180915260:0;chr6:0-2016738:0;chr6:2016739-798135:1;chr6:53249385-57980184:-1;chr6:53589632-56459941:-1;chr6:57980185-171115067:0;chr6:798136-53249384:0;chr7:0-77107:0;chr7:111177823-127360142:0;chr7:111435069-111177822:1;chr7:127360143-127515547:-1;chr7:127515548-159138663:0;chr7:17709177-29656514:0;chr7:190086-2624050:-1;chr7:20213426-22077944:0;chr7:20213706-20213425:1;chr7:22077945-24091487:-1;chr7:23592894-28610322:-1;chr7:23978769-75313182:0;chr7:25286087-28255933:-1;chr7:25432806-25504900:-1;chr7:25504856-187918:1;chr7:2624051-20213705:0;chr7:28610323-29470072:0;chr7:29470073-17709176:1;chr7:29656515-23978768:1;chr7:75313183-75313243:-1;chr7:75313244-111435068:0;chr7:77108-2613183:-1;chr8:0-4343663:0;chr8:103700702-146364022:0;chr8:117067438-119068885:0;chr8:119068886-120282083:-1;chr8:120282084-120744903:0;chr8:120744904-103700701:1;chr8:4343664-4343801:-1;chr8:4343802-98073680:0;chr8:98073681-117067437:-1;chr9:0-21843131:0;chr9:21702639-76746066:0;chr9:21843132-21702638:1;chr9:76643326-141213431:0;chr9:76746067-76643325:1;chrX:0-32006599:0;chrX:154891332-155027814:-1;chrX:155027815-155270560:0;chrX:31843569-154891331:0;chrX:32006600-31843568:1;chrY:0-59373566:0 hs1:1768656-1768656,hs1:1048549-1048549;hs1:1965658-1965658,hs1:2431912-2431912;hs1:4842196-4842196,hs16:65246487-65246487;hs1:4844037-4844037,hs1:14039961-14039961;hs1:5516613-5516613,hs1:17291535-17291535;hs1:6081499-6081499,hs6:798519-798519;hs1:8554864-8554864,hs6:1954748-1954748;hs1:8881757-8881757,hs6:2297520-2297520;hs1:8967633-8967633,hs6:326777-326777;hs1:10009076-10009076,hs6:333514-333514;hs1:11752401-11752401,hs1:12790492-12790492;hs1:12669887-12669887,hs1:66353960-66353960;hs1:12790571-12790571,hs1:12787724-12787724;hs1:14401077-14401077,hs1:63405130-63405130;hs1:14406798-14406798,hs1:62276106-62276106;hs1:17390268-17390268,hs1:63454211-63454211;hs1:17469325-17469325,hs1:65265182-65265182;hs1:19955956-19955956,hs1:19346990-19346990;hs1:47464710-47464710,hs7:34530710-34530710;hs1:55201647-55201647,hs1:19164736-19164736;hs1:61818289-61818289,hs6:2239026-2239026;hs1:62456418-62456418,hs1:63606945-63606945;hs1:63889717-63889717,hs1:16912409-16912409;hs1:63996133-63996133,hs1:75710670-75710670;hs1:66419342-66419342,hs6:124819095-124819095;hs1:73812132-73812132,hs1:67574236-67574236;hs1:74339227-74339227,hs1:71292844-71292844;hs1:74971859-74971859,hs1:61987283-61987283;hs1:201050498-201050498,hs12:60574660-60574660;hs1:201050675-201050675,hs3:158091987-158091987;hs11:7047008-7047008,hs11:25813157-25813157;hs11:28104257-28104257,hs7:117484163-117484163;hs11:28483329-28483329,hs14:40305885-40305885;hs11:30813838-30813838,hs3:158251193-158251193;hs11:30888502-30888502,hs14:40285793-40285793;hs11:58034823-58034823,hsX:110189583-110189583;hs11:76093083-76093083,hs7:39849748-39849748;hs11:91916354-91916354,hs11:89934718-89934718;hs11:92071565-92071565,hs11:120594309-120594309;hs11:103116392-103116392,hs14:37640904-37640904;hs11:103227483-103227483,hs7:1646854-1646854;hs11:107379474-107379474,hs11:28183191-28183191;hs11:118024835-118024835,hs11:121004930-121004930;hs11:120590723-120590723,hs11:98428864-98428864;hs11:120670011-120670011,hs11:122191840-122191840;hs11:122180583-122180583,hs7:41744491-41744491;hs11:122185236-122185236,hs7:43310663-43310663;hs12:27442290-27442290,hs2:227120941-227120941;hs12:56549771-56549771,hs2:231983613-231983613;hs12:58061041-58061041,hs3:151357468-151357468;hs12:58097658-58097658,hs3:90167880-90167880;hs12:58116470-58116470,hs6:53784751-53784751;hs12:58147805-58147805,hs3:148757837-148757837;hs12:58166720-58166720,hs12:69546721-69546721;hs12:58185341-58185341,hs8:59135051-59135051;hs12:58496073-58496073,hs6:52959978-52959978;hs12:58726857-58726857,hs12:64469373-64469373;hs12:58729512-58729512,hs2:86829659-86829659;hs12:58768966-58768966,hs3:137782464-137782464;hs12:58769595-58769595,hs3:66155034-66155034;hs12:58769877-58769877,hs3:137782682-137782682;hs12:58770005-58770005,hs3:66154504-66154504;hs12:58770025-58770025,hs3:90034375-90034375;hs12:58773579-58773579,hs3:137783291-137783291;hs12:58776068-58776068,hs3:156808327-156808327;hs12:58896375-58896375,hs12:76195900-76195900;hs12:58899515-58899515,hs12:69556862-69556862;hs12:59062028-59062028,hs2:83555059-83555059;hs12:59097387-59097387,hs12:76215772-76215772;hs12:59203960-59203960,hs12:76196989-76196989;hs12:59687150-59687150,hs3:66279326-66279326;hs12:59698290-59698290,hs3:66279149-66279149;hs12:60181448-60181448,hs6:63698554-63698554;hs12:60305089-60305089,hs2:85220712-85220712;hs12:60323915-60323915,hs12:60573049-60573049;hs12:60324341-60324341,hs12:60307004-60307004;hs12:60374691-60374691,hs12:62997031-62997031;hs12:60575528-60575528,hs3:158114307-158114307;hs12:60599965-60599965,hs3:158128206-158128206;hs12:60804668-60804668,hs3:152379044-152379044;hs12:61419666-61419666,hs12:61421835-61421835;hs12:62996343-62996343,hs2:81455318-81455318;hs12:62997044-62997044,hs2:85421302-85421302;hs12:64607688-64607688,hs2:75643754-75643754;hs12:64696526-64696526,hs12:63966995-63966995;hs12:64711959-64711959,hs2:86826109-86826109;hs12:65386653-65386653,hs2:84824768-84824768;hs12:67748681-67748681,hs2:85658282-85658282;hs12:67821707-67821707,hs8:20880532-20880532;hs12:68011739-68011739,hs12:68011838-68011838;hs12:68019505-68019505,hs3:153710579-153710579;hs12:68235090-68235090,hs2:85273728-85273728;hs12:68316190-68316190,hs12:71973506-71973506;hs12:68316316-68316316,hs12:68316687-68316687;hs12:69024789-69024789,hs3:157253349-157253349;hs12:69223929-69223929,hs12:68315851-68315851;hs12:69230191-69230191,hs3:156728318-156728318;hs12:69270765-69270765,hs12:69268417-69268417;hs12:69290011-69290011,hs3:159017026-159017026;hs12:69325374-69325374,hs12:69325066-69325066;hs12:69536099-69536099,hs12:76213049-76213049;hs12:69543617-69543617,hs12:69532288-69532288;hs12:70924259-70924259,hs3:162060073-162060073;hs12:71371502-71371502,hs3:149828939-149828939;hs12:71381083-71381083,hs2:85093644-85093644;hs12:71586039-71586039,hs3:149675010-149675010;hs12:71601735-71601735,hs3:149810773-149810773;hs12:72052651-72052651,hs2:85058126-85058126;hs12:72109729-72109729,hs2:85620315-85620315;hs12:72237724-72237724,hs2:127736007-127736007;hs12:72562098-72562098,hs3:183062980-183062980;hs12:72696373-72696373,hs2:87952590-87952590;hs12:75548790-75548790,hs2:76885025-76885025;hs12:75566600-75566600,hs2:76610294-76610294;hs12:75705339-75705339,hs12:64611548-64611548;hs12:75941180-75941180,hs2:84605228-84605228;hs12:76171430-76171430,hs12:70603203-70603203;hs12:76198518-76198518,hs12:65385092-65385092;hs12:76209855-76209855,hs3:148732222-148732222;hs12:77675783-77675783,hs3:183052906-183052906;hs12:77965358-77965358,hs12:69325077-69325077;hs12:82586022-82586022,hs12:78865782-78865782;hs12:84049077-84049077,hs12:69501609-69501609;hs13:46037379-46037379,hs2:84696307-84696307;hs13:74446979-74446979,hs13:74473757-74473757;hs13:74458161-74458161,hs13:74472374-74472374;hs13:74473353-74473353,hs13:74442669-74442669;hs14:29001112-29001112,hs7:51197681-51197681;hs14:30456075-30456075,hs11:28160987-28160987;hs14:33091859-33091859,hs11:26013199-26013199;hs14:40005337-40005337,hs5:26921055-26921055;hs14:50432912-50432912,hs11:28113196-28113196;hs14:54983153-54983153,hs14:69387876-69387876;hs14:72465773-72465773,hs14:71213910-71213910;hs14:83152559-83152559,hs14:83152924-83152924;hs14:101972372-101972372,hs14:101991402-101991402;hs14:101975757-101975757,hs14:83198449-83198449;hs14:102553765-102553765,hs14:93806060-93806060;hs15:35106835-35106835,hs15:44450313-44450313;hs15:35109595-35109595,hs8:130756708-130756708;hs15:42589429-42589429,hs15:99588258-99588258;hs15:59888687-59888687,hs18:445312-445312;hs15:85474598-85474598,hs3:129313584-129313584;hs15:85479940-85479940,hs3:129313579-129313579;hs15:89063343-89063343,hs15:78721419-78721419;hs15:89378709-89378709,hs15:78662267-78662267;hs15:90275521-90275521,hs8:138953654-138953654;hs15:92334271-92334271,hs8:127678987-127678987;hs15:99583769-99583769,hs15:46977019-46977019;hs16:2057362-2057362,hs16:27701200-27701200;hs16:2059211-2059211,hs16:9989564-9989564;hs16:9777515-9777515,hs16:9989232-9989232;hs16:10889040-10889040,hs16:27841354-27841354;hs16:12058169-12058169,hs16:10916228-10916228;hs16:13645640-13645640,hs16:22828362-22828362;hs16:17296250-17296250,hs16:17293198-17293198;hs16:22837818-22837818,hs16:2097437-2097437;hs16:22842477-22842477,hs16:22829377-22829377;hs16:25745061-25745061,hs20:59779554-59779554;hs16:27838024-27838024,hs16:9301059-9301059;hs16:65259449-65259449,hs1:5246295-5246295;hs17:7589856-7589856,hs10:125749269-125749269;hs17:36737273-36737273,hs17:36754622-36754622;hs18:55275437-55275437,hs18:55243619-55243619;hs18:55667342-55667342,hs2:46230204-46230204;hs18:55974402-55974402,hs2:51752566-51752566;hs18:57465656-57465656,hs2:57859509-57859509;hs18:59932768-59932768,hs18:59956204-59956204;hs2:1641633-1641633,hs2:43164392-43164392;hs2:1642560-1642560,hs2:24323767-24323767;hs2:4087789-4087789,hs18:55668399-55668399;hs2:6230439-6230439,hs2:49979484-49979484;hs2:6392694-6392694,hs2:6393728-6393728;hs2:6409617-6409617,hs2:6398336-6398336;hs2:7383097-7383097,hs18:57470314-57470314;hs2:23129599-23129599,hs18:59951546-59951546;hs2:24349236-24349236,hs2:43055895-43055895;hs2:27573649-27573649,hs2:27573262-27573262;hs2:27591411-27591411,hs2:46100103-46100103;hs2:44638784-44638784,hs2:24342546-24342546;hs2:49977443-49977443,hs2:6331570-6331570;hs2:50007316-50007316,hs18:57465388-57465388;hs2:52986248-52986248,hs2:7334658-7334658;hs2:52997751-52997751,hs18:59308412-59308412;hs2:57832660-57832660,hs18:57465248-57465248;hs2:57835798-57835798,hs2:50794316-50794316;hs2:57854855-57854855,hs2:6408153-6408153;hs2:74403990-74403990,hs12:56549684-56549684;hs2:74732561-74732561,hs12:75618796-75618796;hs2:75677572-75677572,hs12:65048961-65048961;hs2:75757134-75757134,hs12:59787103-59787103;hs2:75811317-75811317,hs3:148418190-148418190;hs2:75850939-75850939,hs3:148381415-148381415;hs2:76286058-76286058,hs3:132582613-132582613;hs2:76477566-76477566,hs12:70620354-70620354;hs2:76510089-76510089,hs3:152310308-152310308;hs2:76793427-76793427,hs12:68426751-68426751;hs2:79321333-79321333,hs12:77132624-77132624;hs2:81220699-81220699,hs2:81456974-81456974;hs2:81406026-81406026,hs12:60307616-60307616;hs2:81429224-81429224,hs12:69348534-69348534;hs2:81454600-81454600,hs3:158126223-158126223;hs2:83582832-83582832,hs3:151778291-151778291;hs2:83597183-83597183,hs3:136902961-136902961;hs2:84164294-84164294,hs12:68011755-68011755;hs2:84366542-84366542,hs12:69418559-69418559;hs2:84633610-84633610,hs12:66119864-66119864;hs2:84811011-84811011,hs2:87059238-87059238;hs2:85067187-85067187,hs12:58677471-58677471;hs2:85107503-85107503,hs3:148719271-148719271;hs2:85217652-85217652,hs2:85773770-85773770;hs2:85220109-85220109,hs12:69399244-69399244;hs2:85222788-85222788,hs3:151462522-151462522;hs2:85266907-85266907,hs12:60325985-60325985;hs2:85274833-85274833,hs12:68227066-68227066;hs2:85379565-85379565,hs12:63186223-63186223;hs2:85423467-85423467,hs2:85697069-85697069;hs2:85512995-85512995,hs2:81209345-81209345;hs2:85694537-85694537,hs12:67594574-67594574;hs2:85741879-85741879,hs3:155256692-155256692;hs2:85826726-85826726,hs6:46277758-46277758;hs2:86098921-86098921,hs12:57702492-57702492;hs2:88310587-88310587,hs12:67061283-67061283;hs2:88333656-88333656,hs12:66863196-66863196;hs2:118835835-118835835,hs2:123689549-123689549;hs2:122973135-122973135,hs22:36173561-36173561;hs2:124736706-124736706,hs2:124646390-124646390;hs2:127257330-127257330,hs8:81486742-81486742;hs2:127258958-127258958,hs22:32668000-32668000;hs2:138926091-138926091,hs6:50915107-50915107;hs2:144160940-144160940,hs7:203083-203083;hs2:144166035-144166035,hs11:79399025-79399025;hs2:144537252-144537252,hs7:38650666-38650666;hs2:227107489-227107489,hs15:85474484-85474484;hs2:227107832-227107832,hs12:120743942-120743942;hs20:31232663-31232663,hs1:249239374-249239374;hs20:32956580-32956580,hs9:15719994-15719994;hs20:38185268-38185268,hs9:15124434-15124434;hs20:40507355-40507355,hs3:5987508-5987508;hs20:45875461-45875461,hs15:77518684-77518684;hs20:51753596-51753596,hs7:2458577-2458577;hs20:57606020-57606020,hs5:17449153-17449153;hs21:10558568-10558568,hs3:148726476-148726476;hs21:10560195-10560195,hs12:76092703-76092703;hs22:18161157-18161157,hs22:17035742-17035742;hs22:32814657-32814657,hs22:23406855-23406855;hs22:34545173-34545173,hs2:112250788-112250788;hs22:37088698-37088698,hs2:112475745-112475745;hs22:37320579-37320579,hs2:116845524-116845524;hs22:40683009-40683009,hs22:40685328-40685328;hs3:537507-537507,hs3:2137994-2137994;hs3:2100186-2100186,hs3:445118-445118;hs3:2113650-2113650,hs3:2136688-2136688;hs3:2871966-2871966,hs3:2735038-2735038;hs3:3773279-3773279,hs13:83455621-83455621;hs3:11624820-11624820,hs12:59687782-59687782;hs3:58448854-58448854,hs12:58775440-58775440;hs3:58449203-58449203,hs6:56162726-56162726;hs3:61901652-61901652,hs8:40424316-40424316;hs3:61903121-61903121,hs12:58771598-58771598;hs3:62105732-62105732,hs12:58116848-58116848;hs3:65761077-65761077,hs12:58075167-58075167;hs3:66134364-66134364,hs3:66136001-66136001;hs3:66156241-66156241,hs12:58773391-58773391;hs3:66156460-66156460,hs6:56162329-56162329;hs3:66157125-66157125,hs12:68041345-68041345;hs3:66278253-66278253,hs8:58928686-58928686;hs3:66278597-66278597,hs8:20881373-20881373;hs3:86994474-86994474,hs8:58980450-58980450;hs3:89156208-89156208,hs3:89651383-89651383;hs3:89651256-89651256,hs12:58774856-58774856;hs3:90036084-90036084,hs12:67822188-67822188;hs3:90137600-90137600,hs6:63698109-63698109;hs3:90167658-90167658,hs6:53605781-53605781;hs3:90175515-90175515,hs8:20880666-20880666;hs3:136038590-136038590,hs3:132610158-132610158;hs3:137765978-137765978,hs6:53784563-53784563;hs3:137783014-137783014,hs3:66156437-66156437;hs3:137785551-137785551,hs3:137774498-137774498;hs3:137787085-137787085,hs8:37867825-37867825;hs3:138364674-138364674,hs12:58096044-58096044;hs3:139067245-139067245,hs3:135454777-135454777;hs3:140577480-140577480,hs12:58719877-58719877;hs3:140964416-140964416,hs12:63970109-63970109;hs3:142623656-142623656,hs12:61421044-61421044;hs3:147218103-147218103,hs3:142623032-142623032;hs3:147562554-147562554,hs2:76043614-76043614;hs3:147579111-147579111,hs12:70620264-70620264;hs3:148388578-148388578,hs3:156742916-156742916;hs3:148595128-148595128,hs2:84721728-84721728;hs3:148736616-148736616,hs3:148759378-148759378;hs3:148766246-148766246,hs12:76203894-76203894;hs3:149805327-149805327,hs2:85007581-85007581;hs3:149830314-149830314,hs12:58147368-58147368;hs3:150380570-150380570,hs2:76036779-76036779;hs3:151354281-151354281,hs12:69347070-69347070;hs3:151459853-151459853,hs6:51901184-51901184;hs3:151462519-151462519,hs12:67600795-67600795;hs3:152386051-152386051,hs12:72061282-72061282;hs3:153013469-153013469,hs3:153015907-153015907;hs3:153375572-153375572,hs12:71441124-71441124;hs3:153653687-153653687,hs12:71673039-71673039;hs3:153672347-153672347,hs2:84856057-84856057;hs3:153976364-153976364,hs3:155158517-155158517;hs3:155268369-155268369,hs2:85079236-85079236;hs3:156714130-156714130,hs12:71315393-71315393;hs3:156728266-156728266,hs3:161198815-161198815;hs3:156807794-156807794,hs12:58775654-58775654;hs3:156808124-156808124,hs3:66278210-66278210;hs3:156808364-156808364,hs6:53633692-53633692;hs3:156808376-156808376,hs6:53249534-53249534;hs3:157162510-157162510,hs2:85696689-85696689;hs3:157395691-157395691,hs3:152303877-152303877;hs3:157409535-157409535,hs3:66278690-66278690;hs3:157418201-157418201,hs3:157417439-157417439;hs3:157418818-157418818,hs6:52957946-52957946;hs3:158127769-158127769,hs2:85443278-85443278;hs3:158261868-158261868,hs12:60994802-60994802;hs3:159641542-159641542,hs6:48882971-48882971;hs3:183053175-183053175,hs12:63715434-63715434;hs5:11957267-11957267,hs11:131549899-131549899;hs5:13066807-13066807,hs20:58554060-58554060;hs5:26600092-26600092,hs11:110618245-110618245;hs5:50940489-50940489,hs11:114230357-114230357;hs6:737874-737874,hs1:8967254-8967254;hs6:747388-747388,hs1:9933487-9933487;hs6:1624718-1624718,hs1:17400440-17400440;hs6:1996067-1996067,hs1:63974109-63974109;hs6:2101903-2101903,hs17:7585759-7585759;hs6:2348262-2348262,hs1:63282947-63282947;hs6:2350937-2350937,hs1:63898741-63898741;hs6:15026550-15026550,hs6:16570855-16570855;hs6:36468297-36468297,hs17:7589880-7589880;hs6:48892461-48892461,hs6:48892716-48892716;hs6:48892461-48892461,hs6:48892724-48892724;hs6:48956494-48956494,hs21:38832706-38832706;hs6:52958172-52958172,hs8:20881386-20881386;hs6:52958176-52958176,hs6:69079885-69079885;hs6:53221664-53221664,hs6:64279277-64279277;hs6:53221974-53221974,hs3:66161364-66161364;hs6:53558059-53558059,hs8:40811320-40811320;hs6:53611768-53611768,hs8:58928094-58928094;hs6:53616042-53616042,hs3:137759203-137759203;hs6:56163001-56163001,hs8:20881224-20881224;hs6:56461807-56461807,hs8:37563592-37563592;hs6:57979984-57979984,hs3:158370120-158370120;hs6:62197754-62197754,hs3:137771862-137771862;hs6:62496632-62496632,hs6:69062471-69062471;hs6:62496793-62496793,hs3:90138197-90138197;hs6:63698813-63698813,hs12:58776884-58776884;hs6:63698853-63698853,hs3:66286954-66286954;hs6:64026934-64026934,hs8:20879146-20879146;hs6:64279420-64279420,hs12:58829841-58829841;hs6:64289165-64289165,hs6:62496554-62496554;hs6:64289254-64289254,hs3:66278041-66278041;hs6:64289294-64289294,hs12:58769154-58769154;hs6:69062639-69062639,hs3:89651072-89651072;hs6:69079165-69079165,hs3:90036497-90036497;hs6:69079333-69079333,hs3:90036576-90036576;hs6:69081202-69081202,hs3:138352569-138352569;hs7:2130205-2130205,hs7:4151992-4151992;hs7:2624111-2624111,hs20:51755127-51755127;hs7:3302199-3302199,hs14:33222083-33222083;hs7:3787012-3787012,hs11:30938926-30938926;hs7:4423609-4423609,hs15:44453159-44453159;hs7:4896321-4896321,hs15:41567964-41567964;hs7:6240353-6240353,hs5:25326624-25326624;hs7:13574507-13574507,hs6:63343728-63343728;hs7:16111847-16111847,hs7:15276322-15276322;hs7:16182868-16182868,hs7:16135641-16135641;hs7:19715528-19715528,hs15:27088358-27088358;hs7:20405360-20405360,hs17:80060460-80060460;hs7:23582343-23582343,hs7:27250940-27250940;hs7:25415085-25415085,hs7:2902135-2902135;hs7:27210700-27210700,hs15:25018093-25018093;hs7:27241306-27241306,hs16:27361463-27361463;hs7:27620286-27620286,hs7:28720174-28720174;hs7:28245344-28245344,hs7:16083896-16083896;hs7:29376426-29376426,hs7:28590965-28590965;hs7:29452804-29452804,hs7:29476564-29476564;hs7:29469566-29469566,hs7:38664624-38664624;hs7:30764263-30764263,hs7:29656295-29656295;hs7:30785405-30785405,hs7:104325-104325;hs7:32527342-32527342,hs5:11570983-11570983;hs7:33625436-33625436,hs7:16078616-16078616;hs7:44745480-44745480,hs11:30892887-30892887;hs7:137027642-137027642,hs14:37649318-37649318;hs7:138437892-138437892,hs20:62484304-62484304;hs7:150511927-150511927,hs11:100820379-100820379;hs8:9064239-9064239,hs12:58098035-58098035;hs8:20880263-20880263,hs3:11624835-11624835;hs8:20881574-20881574,hs3:137784340-137784340;hs8:37634582-37634582,hs3:65781251-65781251;hs8:37867786-37867786,hs6:64027393-64027393;hs8:37868301-37868301,hs12:58773414-58773414;hs8:40418390-40418390,hs12:58775057-58775057;hs8:40418864-40418864,hs6:126036048-126036048;hs8:40419038-40419038,hs8:58980760-58980760;hs8:40811936-40811936,hs3:66134814-66134814;hs8:58940568-58940568,hs6:53558136-53558136;hs8:58980491-58980491,hs12:58806466-58806466;hs8:58980675-58980675,hs3:86994715-86994715;hs8:59084403-59084403,hs12:58316989-58316989;hs8:59241733-59241733,hs3:66152842-66152842;hs8:85246822-85246822,hs15:48672066-48672066;hs8:100465690-100465690,hs8:102383415-102383415;hs8:100468781-100468781,hs8:119243808-119243808;hs8:103718571-103718571,hs8:103717197-103717197;hs8:104242316-104242316,hs15:92297857-92297857;hs8:104255990-104255990,hs8:127700862-127700862;hs8:118916762-118916762,hs8:104242494-104242494;hs8:134040576-134040576,hs8:140052716-140052716;hs8:140713975-140713975,hs8:137706390-137706390;hs9:16600663-16600663,hs20:59201038-59201038;hs9:22607038-22607038,hs22:46913921-46913921;hs9:22636111-22636111,hs9:15106012-15106012 Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA Pediatric osteosarcoma is characterized by multiple somatic chromosomal lesions, including structural variations (SVs) and copy number alterations (CNAs). To define the landscape of somatic mutations in pediatric osteosarcoma, we performed whole-genome sequencing of DNA from 20 osteosarcoma tumor samples and matched normal tissue in a discovery cohort, as well as 14 samples in a validation cohort. Single-nucleotide variations (SNVs) exhibited a pattern of localized hypermutation called kataegis in 50% of the tumors. We identified p53 pathway lesions in all tumors in the discovery cohort, nine of which were translocations in the first intron of the TP53 gene. Beyond TP53, the RB1, ATRX, and DLG2 genes showed recurrent somatic alterations in 29%-53% of the tumors. These data highlight the power of whole-genome sequencing for identifying recurrent somatic alterations in cancer genomes that may be missed using other methods. GRCh37/hg19 Yes NA CTDB0380 Research 24703847 Chen X, Bahrami A, Pappo A, Easton J, Dalton J, Hedlund E, Ellison D, Shurtleff S, Wu G, Wei L, Parker M, Rusch M, Nagahawatte P, Wu J, Mao S, Boggs K, Mulder H, Yergeau D, Lu C, Ding L, Edmonson M, Qu C, Wang J, Li Y, Navid F, Daw NC, Mardis ER, Wilson RK, Downing JR, Zhang J, Dyer MA Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma Cell Reports 2014 Apr 17 Osteosarcoma Next Generation Sequencing Homo sapiens SJOS003_D Illumina HiSeq2000 chr10:0-135534747:0;chr11:0-30609357:0;chr11:27499431-135006516:0;chr11:30609358-27499430:1;chr12:0-133067446:0;chr12:133067447-133084731:-1;chr12:133084732-133832553:0;chr12:133832554-133838625:-1;chr12:133838626-133851895:0;chr13:0-96829937:0;chr13:104301412-111931246:0;chr13:111931247-111933135:-1;chr13:111933136-115169878:0;chr13:96829938-104301411:-1;chr14:0-34828349:0;chr14:34828350-67821768:-1;chr14:35974155-65197099:-1;chr14:65004253-65004498:-1;chr14:67821769-107349540:0;chr15:0-66341128:0;chr15:65899226-77202324:0;chr15:66341129-65899225:1;chr15:77202325-81434310:-1;chr15:77202504-77202077:1;chr15:81434311-81573672:0;chr15:81573673-82400998:-1;chr15:82400999-102531392:0;chr16:0-90354753:0;chr17:0-5920:0;chr17:11919890-11942995:-1;chr17:11942996-14900855:0;chr17:13481623-19891583:0;chr17:14900856-13481622:1;chr17:19891584-19892307:-1;chr17:19892308-20070331:0;chr17:20070332-20070716:-1;chr17:20070717-21484903:0;chr17:21484904-37715396:-1;chr17:22095016-22095235:-1;chr17:22095016-22095262:-1;chr17:22180403-22170389:1;chr17:23535-11919889:0;chr17:36663058-76742186:0;chr17:37399995-52244042:-1;chr17:37715485-38587623:-1;chr17:37944199-37945399:-1;chr17:38271150-38034974:1;chr17:38271150-38034997:1;chr17:38722192-41044173:-1;chr17:39781641-69084227:-1;chr17:43122353-39718958:1;chr17:45150715-45860940:-1;chr17:45662983-80426160:0;chr17:46432293-74924040:-1;chr17:49254869-76230415:-1;chr17:50680447-69485386:-1;chr17:51729504-33791132:1;chr17:57623517-41621088:1;chr17:5921-23534:-1;chr17:68116867-57159584:1;chr17:69422372-81195210:0;chr17:71411456-54542603:1;chr17:75954422-20868707:1;chr17:76034913-73935277:1;chr17:76230416-76441210:0;chr17:76441211-36663057:1;chr17:76742187-76742389:-1;chr17:76742390-77149329:0;chr17:77149330-45662982:1;chr17:80426161-69422371:1;chr18:0-4282178:0;chr18:12544893-22519758:0;chr18:22519759-22660301:-1;chr18:22660302-22737219:0;chr18:22737220-23572681:-1;chr18:23572682-78077248:0;chr18:4282179-12544892:-1;chr19:0-59128983:0;chr1:0-8463373:0;chr1:109962608-236879343:0;chr1:114935434-116116839:-1;chr1:116116840-116545188:0;chr1:116545189-118867181:-1;chr1:118867182-151210376:0;chr1:151210377-171929931:-1;chr1:154915339-160836743:-1;chr1:157701861-157211630:1;chr1:169113275-156760680:1;chr1:171929932-177017242:0;chr1:177017243-109962607:1;chr1:236879344-243905502:-1;chr1:243905503-243979639:0;chr1:243979640-243980266:-1;chr1:243980267-249250621:0;chr1:68885150-114935433:0;chr1:68889107-68885149:1;chr1:8459514-68889106:0;chr1:8463374-8459513:1;chr20:0-61318569:0;chr20:61318516-63025520:0;chr20:61318570-61318515:1;chr21:0-45910534:0;chr21:45910477-48129895:0;chr21:45910535-45910476:1;chr22:0-47142216:0;chr22:46970768-51304566:0;chr22:47142217-47176986:-1;chr22:47176987-47184215:0;chr22:47184216-46970767:1;chr2:0-38524928:0;chr2:155215801-243199373:0;chr2:155217005-155215800:1;chr2:38520165-86684033:0;chr2:38524929-38520164:1;chr2:86684034-9100593:1;chr2:9100594-155217004:0;chr3:0-114187174:0;chr3:114187175-115694718:-1;chr3:115410406-116202339:0;chr3:115694719-115830628:0;chr3:115830629-115410405:1;chr3:116202340-116258260:-1;chr3:116258261-125676910:0;chr3:125676911-125676955:-1;chr3:125676956-142869681:0;chr3:138630075-150105891:0;chr3:142869682-138630074:1;chr3:150105892-154114928:-1;chr3:150193928-150105689:1;chr3:154114929-198022430:0;chr4:0-6363879:0;chr4:16622534-33995510:-1;chr4:17431955-29643921:-1;chr4:18048572-19442595:-1;chr4:19393068-14878969:1;chr4:23731319-48571216:-1;chr4:27847825-17455985:1;chr4:30914089-19540032:1;chr4:34335391-27667349:1;chr4:48571217-191154276:0;chr4:6363880-18793802:-1;chr4:8728687-4224338:1;chr5:0-159456539:0;chr5:159456540-98429052:1;chr5:98429053-180915260:0;chr6:0-20259855:0;chr6:20259856-20259910:-1;chr6:20259911-171115067:0;chr7:0-159122385:0;chr7:159120684-159138663:0;chr7:159122386-159120683:1;chr8:0-53838326:0;chr8:119418603-136289170:0;chr8:119473813-128260574:-1;chr8:128260575-128268349:0;chr8:128268350-130065725:-1;chr8:129438323-128652324:1;chr8:129526527-128705335:1;chr8:130064869-130698420:-1;chr8:130066526-130065897:1;chr8:130066556-130065854:1;chr8:130066625-130063879:1;chr8:130066710-130065845:1;chr8:130698421-130700178:0;chr8:130700179-119418602:1;chr8:136289171-136306005:-1;chr8:136306006-139671304:0;chr8:139073924-144398592:0;chr8:139671305-139073923:1;chr8:144398593-144398647:-1;chr8:144398648-146364022:0;chr8:53838327-55929610:-1;chr8:53874562-56454358:-1;chr8:53896645-55953033:-1;chr8:54785324-60670658:-1;chr8:55947513-53876069:1;chr8:56484159-56525361:-1;chr8:56790264-56790346:-1;chr8:57061567-65845127:-1;chr8:59478424-66125651:-1;chr8:60576448-55318715:1;chr8:61209552-67740290:-1;chr8:63358505-65881244:-1;chr8:63861059-63872897:-1;chr8:63861746-63864412:-1;chr8:63873687-68246029:-1;chr8:64689548-56368662:1;chr8:65225431-60589111:1;chr8:65543935-65546556:-1;chr8:66464653-53734933:1;chr8:67473130-69008314:0;chr8:67574944-67575316:-1;chr8:68215569-63859661:1;chr8:68246030-68531506:0;chr8:68531507-67473129:1;chr8:69008315-79393090:-1;chr8:79393091-79549190:0;chr8:79549191-86245092:-1;chr8:79981303-90751680:0;chr8:80566986-119473812:0;chr8:86245093-90560723:0;chr8:90560724-79981302:1;chr8:90751681-80566985:1;chr9:0-93561722:0;chr9:93561679-141213431:0;chr9:93561723-93561678:1;chrX:0-149730184:0;chrX:149730185-149851548:-1;chrX:149851549-155270560:0;chrY:0-59373566:0 hs1:1768656-1768656,hs1:1048549-1048549;hs1:1965658-1965658,hs1:2431912-2431912;hs1:4842196-4842196,hs16:65246487-65246487;hs1:4844037-4844037,hs1:14039961-14039961;hs1:5516613-5516613,hs1:17291535-17291535;hs1:6081499-6081499,hs6:798519-798519;hs1:8554864-8554864,hs6:1954748-1954748;hs1:8881757-8881757,hs6:2297520-2297520;hs1:8967633-8967633,hs6:326777-326777;hs1:10009076-10009076,hs6:333514-333514;hs1:11752401-11752401,hs1:12790492-12790492;hs1:12669887-12669887,hs1:66353960-66353960;hs1:12790571-12790571,hs1:12787724-12787724;hs1:14401077-14401077,hs1:63405130-63405130;hs1:14406798-14406798,hs1:62276106-62276106;hs1:17390268-17390268,hs1:63454211-63454211;hs1:17469325-17469325,hs1:65265182-65265182;hs1:19955956-19955956,hs1:19346990-19346990;hs1:47464710-47464710,hs7:34530710-34530710;hs1:55201647-55201647,hs1:19164736-19164736;hs1:61818289-61818289,hs6:2239026-2239026;hs1:62456418-62456418,hs1:63606945-63606945;hs1:63889717-63889717,hs1:16912409-16912409;hs1:63996133-63996133,hs1:75710670-75710670;hs1:66419342-66419342,hs6:124819095-124819095;hs1:73812132-73812132,hs1:67574236-67574236;hs1:74339227-74339227,hs1:71292844-71292844;hs1:74971859-74971859,hs1:61987283-61987283;hs1:201050498-201050498,hs12:60574660-60574660;hs1:201050675-201050675,hs3:158091987-158091987;hs11:7047008-7047008,hs11:25813157-25813157;hs11:28104257-28104257,hs7:117484163-117484163;hs11:28483329-28483329,hs14:40305885-40305885;hs11:30813838-30813838,hs3:158251193-158251193;hs11:30888502-30888502,hs14:40285793-40285793;hs11:58034823-58034823,hsX:110189583-110189583;hs11:76093083-76093083,hs7:39849748-39849748;hs11:91916354-91916354,hs11:89934718-89934718;hs11:92071565-92071565,hs11:120594309-120594309;hs11:103116392-103116392,hs14:37640904-37640904;hs11:103227483-103227483,hs7:1646854-1646854;hs11:107379474-107379474,hs11:28183191-28183191;hs11:118024835-118024835,hs11:121004930-121004930;hs11:120590723-120590723,hs11:98428864-98428864;hs11:120670011-120670011,hs11:122191840-122191840;hs11:122180583-122180583,hs7:41744491-41744491;hs11:122185236-122185236,hs7:43310663-43310663;hs12:27442290-27442290,hs2:227120941-227120941;hs12:56549771-56549771,hs2:231983613-231983613;hs12:58061041-58061041,hs3:151357468-151357468;hs12:58097658-58097658,hs3:90167880-90167880;hs12:58116470-58116470,hs6:53784751-53784751;hs12:58147805-58147805,hs3:148757837-148757837;hs12:58166720-58166720,hs12:69546721-69546721;hs12:58185341-58185341,hs8:59135051-59135051;hs12:58496073-58496073,hs6:52959978-52959978;hs12:58726857-58726857,hs12:64469373-64469373;hs12:58729512-58729512,hs2:86829659-86829659;hs12:58768966-58768966,hs3:137782464-137782464;hs12:58769595-58769595,hs3:66155034-66155034;hs12:58769877-58769877,hs3:137782682-137782682;hs12:58770005-58770005,hs3:66154504-66154504;hs12:58770025-58770025,hs3:90034375-90034375;hs12:58773579-58773579,hs3:137783291-137783291;hs12:58776068-58776068,hs3:156808327-156808327;hs12:58896375-58896375,hs12:76195900-76195900;hs12:58899515-58899515,hs12:69556862-69556862;hs12:59062028-59062028,hs2:83555059-83555059;hs12:59097387-59097387,hs12:76215772-76215772;hs12:59203960-59203960,hs12:76196989-76196989;hs12:59687150-59687150,hs3:66279326-66279326;hs12:59698290-59698290,hs3:66279149-66279149;hs12:60181448-60181448,hs6:63698554-63698554;hs12:60305089-60305089,hs2:85220712-85220712;hs12:60323915-60323915,hs12:60573049-60573049;hs12:60324341-60324341,hs12:60307004-60307004;hs12:60374691-60374691,hs12:62997031-62997031;hs12:60575528-60575528,hs3:158114307-158114307;hs12:60599965-60599965,hs3:158128206-158128206;hs12:60804668-60804668,hs3:152379044-152379044;hs12:61419666-61419666,hs12:61421835-61421835;hs12:62996343-62996343,hs2:81455318-81455318;hs12:62997044-62997044,hs2:85421302-85421302;hs12:64607688-64607688,hs2:75643754-75643754;hs12:64696526-64696526,hs12:63966995-63966995;hs12:64711959-64711959,hs2:86826109-86826109;hs12:65386653-65386653,hs2:84824768-84824768;hs12:67748681-67748681,hs2:85658282-85658282;hs12:67821707-67821707,hs8:20880532-20880532;hs12:68011739-68011739,hs12:68011838-68011838;hs12:68019505-68019505,hs3:153710579-153710579;hs12:68235090-68235090,hs2:85273728-85273728;hs12:68316190-68316190,hs12:71973506-71973506;hs12:68316316-68316316,hs12:68316687-68316687;hs12:69024789-69024789,hs3:157253349-157253349;hs12:69223929-69223929,hs12:68315851-68315851;hs12:69230191-69230191,hs3:156728318-156728318;hs12:69270765-69270765,hs12:69268417-69268417;hs12:69290011-69290011,hs3:159017026-159017026;hs12:69325374-69325374,hs12:69325066-69325066;hs12:69536099-69536099,hs12:76213049-76213049;hs12:69543617-69543617,hs12:69532288-69532288;hs12:70924259-70924259,hs3:162060073-162060073;hs12:71371502-71371502,hs3:149828939-149828939;hs12:71381083-71381083,hs2:85093644-85093644;hs12:71586039-71586039,hs3:149675010-149675010;hs12:71601735-71601735,hs3:149810773-149810773;hs12:72052651-72052651,hs2:85058126-85058126;hs12:72109729-72109729,hs2:85620315-85620315;hs12:72237724-72237724,hs2:127736007-127736007;hs12:72562098-72562098,hs3:183062980-183062980;hs12:72696373-72696373,hs2:87952590-87952590;hs12:75548790-75548790,hs2:76885025-76885025;hs12:75566600-75566600,hs2:76610294-76610294;hs12:75705339-75705339,hs12:64611548-64611548;hs12:75941180-75941180,hs2:84605228-84605228;hs12:76171430-76171430,hs12:70603203-70603203;hs12:76198518-76198518,hs12:65385092-65385092;hs12:76209855-76209855,hs3:148732222-148732222;hs12:77675783-77675783,hs3:183052906-183052906;hs12:77965358-77965358,hs12:69325077-69325077;hs12:82586022-82586022,hs12:78865782-78865782;hs12:84049077-84049077,hs12:69501609-69501609;hs13:46037379-46037379,hs2:84696307-84696307;hs13:74446979-74446979,hs13:74473757-74473757;hs13:74458161-74458161,hs13:74472374-74472374;hs13:74473353-74473353,hs13:74442669-74442669;hs14:29001112-29001112,hs7:51197681-51197681;hs14:30456075-30456075,hs11:28160987-28160987;hs14:33091859-33091859,hs11:26013199-26013199;hs14:40005337-40005337,hs5:26921055-26921055;hs14:50432912-50432912,hs11:28113196-28113196;hs14:54983153-54983153,hs14:69387876-69387876;hs14:72465773-72465773,hs14:71213910-71213910;hs14:83152559-83152559,hs14:83152924-83152924;hs14:101972372-101972372,hs14:101991402-101991402;hs14:101975757-101975757,hs14:83198449-83198449;hs14:102553765-102553765,hs14:93806060-93806060;hs15:35106835-35106835,hs15:44450313-44450313;hs15:35109595-35109595,hs8:130756708-130756708;hs15:42589429-42589429,hs15:99588258-99588258;hs15:59888687-59888687,hs18:445312-445312;hs15:85474598-85474598,hs3:129313584-129313584;hs15:85479940-85479940,hs3:129313579-129313579;hs15:89063343-89063343,hs15:78721419-78721419;hs15:89378709-89378709,hs15:78662267-78662267;hs15:90275521-90275521,hs8:138953654-138953654;hs15:92334271-92334271,hs8:127678987-127678987;hs15:99583769-99583769,hs15:46977019-46977019;hs16:2057362-2057362,hs16:27701200-27701200;hs16:2059211-2059211,hs16:9989564-9989564;hs16:9777515-9777515,hs16:9989232-9989232;hs16:10889040-10889040,hs16:27841354-27841354;hs16:12058169-12058169,hs16:10916228-10916228;hs16:13645640-13645640,hs16:22828362-22828362;hs16:17296250-17296250,hs16:17293198-17293198;hs16:22837818-22837818,hs16:2097437-2097437;hs16:22842477-22842477,hs16:22829377-22829377;hs16:25745061-25745061,hs20:59779554-59779554;hs16:27838024-27838024,hs16:9301059-9301059;hs16:65259449-65259449,hs1:5246295-5246295;hs17:7589856-7589856,hs10:125749269-125749269;hs17:36737273-36737273,hs17:36754622-36754622;hs18:55275437-55275437,hs18:55243619-55243619;hs18:55667342-55667342,hs2:46230204-46230204;hs18:55974402-55974402,hs2:51752566-51752566;hs18:57465656-57465656,hs2:57859509-57859509;hs18:59932768-59932768,hs18:59956204-59956204;hs2:1641633-1641633,hs2:43164392-43164392;hs2:1642560-1642560,hs2:24323767-24323767;hs2:4087789-4087789,hs18:55668399-55668399;hs2:6230439-6230439,hs2:49979484-49979484;hs2:6392694-6392694,hs2:6393728-6393728;hs2:6409617-6409617,hs2:6398336-6398336;hs2:7383097-7383097,hs18:57470314-57470314;hs2:23129599-23129599,hs18:59951546-59951546;hs2:24349236-24349236,hs2:43055895-43055895;hs2:27573649-27573649,hs2:27573262-27573262;hs2:27591411-27591411,hs2:46100103-46100103;hs2:44638784-44638784,hs2:24342546-24342546;hs2:49977443-49977443,hs2:6331570-6331570;hs2:50007316-50007316,hs18:57465388-57465388;hs2:52986248-52986248,hs2:7334658-7334658;hs2:52997751-52997751,hs18:59308412-59308412;hs2:57832660-57832660,hs18:57465248-57465248;hs2:57835798-57835798,hs2:50794316-50794316;hs2:57854855-57854855,hs2:6408153-6408153;hs2:74403990-74403990,hs12:56549684-56549684;hs2:74732561-74732561,hs12:75618796-75618796;hs2:75677572-75677572,hs12:65048961-65048961;hs2:75757134-75757134,hs12:59787103-59787103;hs2:75811317-75811317,hs3:148418190-148418190;hs2:75850939-75850939,hs3:148381415-148381415;hs2:76286058-76286058,hs3:132582613-132582613;hs2:76477566-76477566,hs12:70620354-70620354;hs2:76510089-76510089,hs3:152310308-152310308;hs2:76793427-76793427,hs12:68426751-68426751;hs2:79321333-79321333,hs12:77132624-77132624;hs2:81220699-81220699,hs2:81456974-81456974;hs2:81406026-81406026,hs12:60307616-60307616;hs2:81429224-81429224,hs12:69348534-69348534;hs2:81454600-81454600,hs3:158126223-158126223;hs2:83582832-83582832,hs3:151778291-151778291;hs2:83597183-83597183,hs3:136902961-136902961;hs2:84164294-84164294,hs12:68011755-68011755;hs2:84366542-84366542,hs12:69418559-69418559;hs2:84633610-84633610,hs12:66119864-66119864;hs2:84811011-84811011,hs2:87059238-87059238;hs2:85067187-85067187,hs12:58677471-58677471;hs2:85107503-85107503,hs3:148719271-148719271;hs2:85217652-85217652,hs2:85773770-85773770;hs2:85220109-85220109,hs12:69399244-69399244;hs2:85222788-85222788,hs3:151462522-151462522;hs2:85266907-85266907,hs12:60325985-60325985;hs2:85274833-85274833,hs12:68227066-68227066;hs2:85379565-85379565,hs12:63186223-63186223;hs2:85423467-85423467,hs2:85697069-85697069;hs2:85512995-85512995,hs2:81209345-81209345;hs2:85694537-85694537,hs12:67594574-67594574;hs2:85741879-85741879,hs3:155256692-155256692;hs2:85826726-85826726,hs6:46277758-46277758;hs2:86098921-86098921,hs12:57702492-57702492;hs2:88310587-88310587,hs12:67061283-67061283;hs2:88333656-88333656,hs12:66863196-66863196;hs2:118835835-118835835,hs2:123689549-123689549;hs2:122973135-122973135,hs22:36173561-36173561;hs2:124736706-124736706,hs2:124646390-124646390;hs2:127257330-127257330,hs8:81486742-81486742;hs2:127258958-127258958,hs22:32668000-32668000;hs2:138926091-138926091,hs6:50915107-50915107;hs2:144160940-144160940,hs7:203083-203083;hs2:144166035-144166035,hs11:79399025-79399025;hs2:144537252-144537252,hs7:38650666-38650666;hs2:227107489-227107489,hs15:85474484-85474484;hs2:227107832-227107832,hs12:120743942-120743942;hs20:31232663-31232663,hs1:249239374-249239374;hs20:32956580-32956580,hs9:15719994-15719994;hs20:38185268-38185268,hs9:15124434-15124434;hs20:40507355-40507355,hs3:5987508-5987508;hs20:45875461-45875461,hs15:77518684-77518684;hs20:51753596-51753596,hs7:2458577-2458577;hs20:57606020-57606020,hs5:17449153-17449153;hs21:10558568-10558568,hs3:148726476-148726476;hs21:10560195-10560195,hs12:76092703-76092703;hs22:18161157-18161157,hs22:17035742-17035742;hs22:32814657-32814657,hs22:23406855-23406855;hs22:34545173-34545173,hs2:112250788-112250788;hs22:37088698-37088698,hs2:112475745-112475745;hs22:37320579-37320579,hs2:116845524-116845524;hs22:40683009-40683009,hs22:40685328-40685328;hs3:537507-537507,hs3:2137994-2137994;hs3:2100186-2100186,hs3:445118-445118;hs3:2113650-2113650,hs3:2136688-2136688;hs3:2871966-2871966,hs3:2735038-2735038;hs3:3773279-3773279,hs13:83455621-83455621;hs3:11624820-11624820,hs12:59687782-59687782;hs3:58448854-58448854,hs12:58775440-58775440;hs3:58449203-58449203,hs6:56162726-56162726;hs3:61901652-61901652,hs8:40424316-40424316;hs3:61903121-61903121,hs12:58771598-58771598;hs3:62105732-62105732,hs12:58116848-58116848;hs3:65761077-65761077,hs12:58075167-58075167;hs3:66134364-66134364,hs3:66136001-66136001;hs3:66156241-66156241,hs12:58773391-58773391;hs3:66156460-66156460,hs6:56162329-56162329;hs3:66157125-66157125,hs12:68041345-68041345;hs3:66278253-66278253,hs8:58928686-58928686;hs3:66278597-66278597,hs8:20881373-20881373;hs3:86994474-86994474,hs8:58980450-58980450;hs3:89156208-89156208,hs3:89651383-89651383;hs3:89651256-89651256,hs12:58774856-58774856;hs3:90036084-90036084,hs12:67822188-67822188;hs3:90137600-90137600,hs6:63698109-63698109;hs3:90167658-90167658,hs6:53605781-53605781;hs3:90175515-90175515,hs8:20880666-20880666;hs3:136038590-136038590,hs3:132610158-132610158;hs3:137765978-137765978,hs6:53784563-53784563;hs3:137783014-137783014,hs3:66156437-66156437;hs3:137785551-137785551,hs3:137774498-137774498;hs3:137787085-137787085,hs8:37867825-37867825;hs3:138364674-138364674,hs12:58096044-58096044;hs3:139067245-139067245,hs3:135454777-135454777;hs3:140577480-140577480,hs12:58719877-58719877;hs3:140964416-140964416,hs12:63970109-63970109;hs3:142623656-142623656,hs12:61421044-61421044;hs3:147218103-147218103,hs3:142623032-142623032;hs3:147562554-147562554,hs2:76043614-76043614;hs3:147579111-147579111,hs12:70620264-70620264;hs3:148388578-148388578,hs3:156742916-156742916;hs3:148595128-148595128,hs2:84721728-84721728;hs3:148736616-148736616,hs3:148759378-148759378;hs3:148766246-148766246,hs12:76203894-76203894;hs3:149805327-149805327,hs2:85007581-85007581;hs3:149830314-149830314,hs12:58147368-58147368;hs3:150380570-150380570,hs2:76036779-76036779;hs3:151354281-151354281,hs12:69347070-69347070;hs3:151459853-151459853,hs6:51901184-51901184;hs3:151462519-151462519,hs12:67600795-67600795;hs3:152386051-152386051,hs12:72061282-72061282;hs3:153013469-153013469,hs3:153015907-153015907;hs3:153375572-153375572,hs12:71441124-71441124;hs3:153653687-153653687,hs12:71673039-71673039;hs3:153672347-153672347,hs2:84856057-84856057;hs3:153976364-153976364,hs3:155158517-155158517;hs3:155268369-155268369,hs2:85079236-85079236;hs3:156714130-156714130,hs12:71315393-71315393;hs3:156728266-156728266,hs3:161198815-161198815;hs3:156807794-156807794,hs12:58775654-58775654;hs3:156808124-156808124,hs3:66278210-66278210;hs3:156808364-156808364,hs6:53633692-53633692;hs3:156808376-156808376,hs6:53249534-53249534;hs3:157162510-157162510,hs2:85696689-85696689;hs3:157395691-157395691,hs3:152303877-152303877;hs3:157409535-157409535,hs3:66278690-66278690;hs3:157418201-157418201,hs3:157417439-157417439;hs3:157418818-157418818,hs6:52957946-52957946;hs3:158127769-158127769,hs2:85443278-85443278;hs3:158261868-158261868,hs12:60994802-60994802;hs3:159641542-159641542,hs6:48882971-48882971;hs3:183053175-183053175,hs12:63715434-63715434;hs5:11957267-11957267,hs11:131549899-131549899;hs5:13066807-13066807,hs20:58554060-58554060;hs5:26600092-26600092,hs11:110618245-110618245;hs5:50940489-50940489,hs11:114230357-114230357;hs6:737874-737874,hs1:8967254-8967254;hs6:747388-747388,hs1:9933487-9933487;hs6:1624718-1624718,hs1:17400440-17400440;hs6:1996067-1996067,hs1:63974109-63974109;hs6:2101903-2101903,hs17:7585759-7585759;hs6:2348262-2348262,hs1:63282947-63282947;hs6:2350937-2350937,hs1:63898741-63898741;hs6:15026550-15026550,hs6:16570855-16570855;hs6:36468297-36468297,hs17:7589880-7589880;hs6:48892461-48892461,hs6:48892716-48892716;hs6:48892461-48892461,hs6:48892724-48892724;hs6:48956494-48956494,hs21:38832706-38832706;hs6:52958172-52958172,hs8:20881386-20881386;hs6:52958176-52958176,hs6:69079885-69079885;hs6:53221664-53221664,hs6:64279277-64279277;hs6:53221974-53221974,hs3:66161364-66161364;hs6:53558059-53558059,hs8:40811320-40811320;hs6:53611768-53611768,hs8:58928094-58928094;hs6:53616042-53616042,hs3:137759203-137759203;hs6:56163001-56163001,hs8:20881224-20881224;hs6:56461807-56461807,hs8:37563592-37563592;hs6:57979984-57979984,hs3:158370120-158370120;hs6:62197754-62197754,hs3:137771862-137771862;hs6:62496632-62496632,hs6:69062471-69062471;hs6:62496793-62496793,hs3:90138197-90138197;hs6:63698813-63698813,hs12:58776884-58776884;hs6:63698853-63698853,hs3:66286954-66286954;hs6:64026934-64026934,hs8:20879146-20879146;hs6:64279420-64279420,hs12:58829841-58829841;hs6:64289165-64289165,hs6:62496554-62496554;hs6:64289254-64289254,hs3:66278041-66278041;hs6:64289294-64289294,hs12:58769154-58769154;hs6:69062639-69062639,hs3:89651072-89651072;hs6:69079165-69079165,hs3:90036497-90036497;hs6:69079333-69079333,hs3:90036576-90036576;hs6:69081202-69081202,hs3:138352569-138352569;hs7:2130205-2130205,hs7:4151992-4151992;hs7:2624111-2624111,hs20:51755127-51755127;hs7:3302199-3302199,hs14:33222083-33222083;hs7:3787012-3787012,hs11:30938926-30938926;hs7:4423609-4423609,hs15:44453159-44453159;hs7:4896321-4896321,hs15:41567964-41567964;hs7:6240353-6240353,hs5:25326624-25326624;hs7:13574507-13574507,hs6:63343728-63343728;hs7:16111847-16111847,hs7:15276322-15276322;hs7:16182868-16182868,hs7:16135641-16135641;hs7:19715528-19715528,hs15:27088358-27088358;hs7:20405360-20405360,hs17:80060460-80060460;hs7:23582343-23582343,hs7:27250940-27250940;hs7:25415085-25415085,hs7:2902135-2902135;hs7:27210700-27210700,hs15:25018093-25018093;hs7:27241306-27241306,hs16:27361463-27361463;hs7:27620286-27620286,hs7:28720174-28720174;hs7:28245344-28245344,hs7:16083896-16083896;hs7:29376426-29376426,hs7:28590965-28590965;hs7:29452804-29452804,hs7:29476564-29476564;hs7:29469566-29469566,hs7:38664624-38664624;hs7:30764263-30764263,hs7:29656295-29656295;hs7:30785405-30785405,hs7:104325-104325;hs7:32527342-32527342,hs5:11570983-11570983;hs7:33625436-33625436,hs7:16078616-16078616;hs7:44745480-44745480,hs11:30892887-30892887;hs7:137027642-137027642,hs14:37649318-37649318;hs7:138437892-138437892,hs20:62484304-62484304;hs7:150511927-150511927,hs11:100820379-100820379;hs8:9064239-9064239,hs12:58098035-58098035;hs8:20880263-20880263,hs3:11624835-11624835;hs8:20881574-20881574,hs3:137784340-137784340;hs8:37634582-37634582,hs3:65781251-65781251;hs8:37867786-37867786,hs6:64027393-64027393;hs8:37868301-37868301,hs12:58773414-58773414;hs8:40418390-40418390,hs12:58775057-58775057;hs8:40418864-40418864,hs6:126036048-126036048;hs8:40419038-40419038,hs8:58980760-58980760;hs8:40811936-40811936,hs3:66134814-66134814;hs8:58940568-58940568,hs6:53558136-53558136;hs8:58980491-58980491,hs12:58806466-58806466;hs8:58980675-58980675,hs3:86994715-86994715;hs8:59084403-59084403,hs12:58316989-58316989;hs8:59241733-59241733,hs3:66152842-66152842;hs8:85246822-85246822,hs15:48672066-48672066;hs8:100465690-100465690,hs8:102383415-102383415;hs8:100468781-100468781,hs8:119243808-119243808;hs8:103718571-103718571,hs8:103717197-103717197;hs8:104242316-104242316,hs15:92297857-92297857;hs8:104255990-104255990,hs8:127700862-127700862;hs8:118916762-118916762,hs8:104242494-104242494;hs8:134040576-134040576,hs8:140052716-140052716;hs8:140713975-140713975,hs8:137706390-137706390;hs9:16600663-16600663,hs20:59201038-59201038;hs9:22607038-22607038,hs22:46913921-46913921;hs9:22636111-22636111,hs9:15106012-hs151060121:109962590-109962590,hs19:19172754-19172754;hs1:112848439-112848439,hs1:167050574-167050574;hs1:116711378-116711378,hs1:166960872-166960872;hs1:162367587-162367587,hs1:110670277-110670277;hs11:30401103-30401103,hs11:25091190-25091190;hs11:30736425-30736425,hs14:77102093-77102093;hs11:31429983-31429983,hs11:22800995-22800995;hs11:79607311-79607311,hs11:79634393-79634393;hs11:80294200-80294200,hs11:79607299-79607299;hs12:133840739-133840739,hs2:37110857-37110857;hs13:97108915-97108915,hs3:148583776-148583776;hs13:97502631-97502631,hs13:97509576-97509576;hs13:102835459-102835459,hs3:148606924-148606924;hs13:105119773-105119773,hs3:149561793-149561793;hs13:108500611-108500611,hs13:96102987-96102987;hs14:28681314-28681314,hs14:20926259-20926259;hs14:34824046-34824046,hs14:34821743-34821743;hs14:49174458-49174458,hs3:157793386-157793386;hs14:51311458-51311458,hs14:79854603-79854603;hs14:55201369-55201369,hs3:147247056-147247056;hs14:58390173-58390173,hs14:50778674-50778674;hs14:61312550-61312550,hs14:69158577-69158577;hs14:72718452-72718452,hs14:80156335-80156335;hs14:77118535-77118535,hs19:58884443-58884443;hs14:77335495-77335495,hs14:79979263-79979263;hs14:79852144-79852144,hs14:53947450-53947450;hs14:80021817-80021817,hs14:79786335-79786335;hs15:76436075-76436075,hs15:83742270-83742270;hs15:79530825-79530825,hs15:96723486-96723486;hs15:81577280-81577280,hs15:81226111-81226111;hs15:82366600-82366600,hs15:81434726-81434726;hs15:82391496-82391496,hs15:77202219-77202219;hs15:84711038-84711038,hs15:74693082-74693082;hs15:96375633-96375633,hs15:100850957-100850957;hs17:7586251-7586251,hs3:158530829-158530829;hs17:10007933-10007933,hs17:19297874-19297874;hs17:10922586-10922586,hs8:79555796-79555796;hs17:10938697-10938697,hs3:116586825-116586825;hs17:11748205-11748205,hs8:79552654-79552654;hs17:11956718-11956718,hs1:226135548-226135548;hs17:12964740-12964740,hs17:13052366-13052366;hs17:12984782-12984782,hs3:115864865-115864865;hs17:13039031-13039031,hs17:10949293-10949293;hs17:13060930-13060930,hs8:55537230-55537230;hs17:13481410-13481410,hs8:60522252-60522252;hs17:15278501-15278501,hs8:72686592-72686592;hs17:22171186-22171186,hs8:56446675-56446675;hs17:25586475-25586475,hs17:74720993-74720993;hs17:25588886-25588886,hs17:51377486-51377486;hs17:32368984-32368984,hs17:33498939-33498939;hs17:36892338-36892338,hs17:74114053-74114053;hs17:38888969-38888969,hs17:50677416-50677416;hs17:40538097-40538097,hs17:75721950-75721950;hs17:42736230-42736230,hs17:32546113-32546113;hs17:47413166-47413166,hs17:37718582-37718582;hs17:51097077-51097077,hs17:58686060-58686060;hs17:51522030-51522030,hs17:31955287-31955287;hs17:52238261-52238261,hs17:22259461-22259461;hs17:54098880-54098880,hs17:58715549-58715549;hs17:60120162-60120162,hs17:51357154-51357154;hs17:61408375-61408375,hs17:62317755-62317755;hs17:64110827-64110827,hs17:69281375-69281375;hs17:69577873-69577873,hs17:73873731-73873731;hs17:72707622-72707622,hs17:57159561-57159561;hs17:79570800-79570800,hs17:50679280-50679280;hs18:65399911-65399911,hs17:14872456-14872456;hs19:13047288-13047288,hs5:157232247-157232247;hs19:19172760-19172760,hs19:13046775-13046775;hs19:30186588-30186588,hs14:44440442-44440442;hs19:58897567-58897567,hs19:58897854-58897854;hs2:9567993-9567993,hs3:158530787-158530787;hs2:123370238-123370238,hs2:123369988-123369988;hs3:102703892-102703892,hs3:103299902-103299902;hs3:114187937-114187937,hs17:12962428-12962428;hs3:114785909-114785909,hs17:11385676-11385676;hs3:115436732-115436732,hs8:79527391-79527391;hs3:115443898-115443898,hs8:86213826-86213826;hs3:115731230-115731230,hs17:10949457-10949457;hs3:115851715-115851715,hs17:10913868-10913868;hs3:116104081-116104081,hs8:80544491-80544491;hs3:116434619-116434619,hs8:55804757-55804757;hs3:138646949-138646949,hs3:139629693-139629693;hs3:142801339-142801339,hs3:143908011-143908011;hs3:145092241-145092241,hs13:97109814-97109814;hs3:145406282-145406282,hs14:48993996-48993996;hs3:147245118-147245118,hs3:151254570-151254570;hs3:148166058-148166058,hs13:97090611-97090611;hs3:148256752-148256752,hs3:147246483-147246483;hs3:148607084-148607084,hs13:102141836-102141836;hs3:150832870-150832870,hs14:48286614-48286614;hs3:154216706-154216706,hs3:146055728-146055728;hs4:4304546-4304546,hs4:28785295-28785295;hs4:4503435-4503435,hs4:29597905-29597905;hs4:11086354-11086354,hs4:19462632-19462632;hs4:14844051-14844051,hs4:16669696-16669696;hs4:18435541-18435541,hs4:4358842-4358842;hs4:18784398-18784398,hs4:18785958-18785958;hs4:23920418-23920418,hs4:23731137-23731137;hs4:26305297-26305297,hs4:31517735-31517735;hs4:26481849-26481849,hs4:31516691-31516691;hs4:26699051-26699051,hs4:29559790-29559790;hs4:26702833-26702833,hs4:5894311-5894311;hs4:26816868-26816868,hs4:26818258-26818258;hs4:26817028-26817028,hs4:17424956-17424956;hs4:27860093-27860093,hs4:11120543-11120543;hs4:29559798-29559798,hs4:16669213-16669213;hs4:31503541-31503541,hs4:29558706-29558706;hs5:4333739-4333739,hs5:4332776-4332776;hs5:7785950-7785950,hs12:128750293-128750293;hs5:8790376-8790376,hs1:236850501-236850501;hs6:89140899-89140899,hs3:150863054-150863054;hs6:89141054-89141054,hs3:150863935-150863935;hs6:98222103-98222103,hs3:103079074-103079074;hs6:137532597-137532597,hs6:131693199-131693199;hs8:52793780-52793780,hs8:53963832-53963832;hs8:53764530-53764530,hs8:51892534-51892534;hs8:54505914-54505914,hs8:53008144-53008144;hs8:54770874-54770874,hs8:54770054-54770054;hs8:55317881-55317881,hs8:60521755-60521755;hs8:55716023-55716023,hs3:114180050-114180050;hs8:55926294-55926294,hs17:14901300-14901300;hs8:56363365-56363365,hs8:56453103-56453103;hs8:56414387-56414387,hs17:22074375-22074375;hs8:56692727-56692727,hs17:10007892-10007892;hs8:56795664-56795664,hs8:63697198-63697198;hs8:56876953-56876953,hs8:65845040-65845040;hs8:57058190-57058190,hs8:56867910-56867910;hs8:59213598-59213598,hs8:65969835-65969835;hs8:60676549-60676549,hs8:60677573-60677573;hs8:61229169-61229169,hs17:19279470-19279470;hs8:63692513-63692513,hs8:58687421-58687421;hs8:63838911-63838911,hs17:9954729-9954729;hs8:63849994-63849994,hs8:65931260-65931260;hs8:63852228-63852228,hs17:19320472-19320472;hs8:64519996-64519996,hs8:60366371-60366371;hs8:64682078-64682078,hs8:53854050-53854050;hs8:65224454-65224454,hs8:56358123-56358123;hs8:65881365-65881365,hs17:13282229-13282229;hs8:68781413-68781413,hs8:55870308-55870308;hs8:68932846-68932846,hs8:82225030-82225030;hs8:70997214-70997214,hs8:71061574-71061574;hs8:71024348-71024348,hs17:11334111-11334111;hs8:71096033-71096033,hs8:70994818-70994818;hs8:79394348-79394348,hs8:139075814-139075814;hs8:79543868-79543868,hs17:13052403-13052403;hs8:79931752-79931752,hs14:39108204-39108204;hs8:79931752-79931752,hs17:11750286-11750286;hs8:79983173-79983173,hs17:11770140-11770140;hs8:86247281-86247281,hs3:115438949-115438949;hs8:86276941-86276941,hs8:90693144-90693144;hs8:86342020-86342020,hs17:12963267-12963267;hs8:86349963-86349963,hs8:79905563-79905563;hs8:90690619-90690619,hs3:116103051-116103051;hs8:90743287-90743287,hs8:90687121-90687121;hs8:128653490-128653490,hs8:130066422-130066422;hs8:130064256-130064256,hs8:128243315-128243315;hs8:130064670-130064670,hs8:130066690-130066690;hs8:132670995-132670995,hs8:128630827-128630827;hs8:139658797-139658797,hs17:9335036-9335036;hs8:144948472-144948472,hs13:113755726-113755726;hs8:144948472-144948472,hs17:7586249-7586249;hs9:30866550-30866550,hs9:68414321-68414321 Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA Pediatric osteosarcoma is characterized by multiple somatic chromosomal lesions, including structural variations (SVs) and copy number alterations (CNAs). To define the landscape of somatic mutations in pediatric osteosarcoma, we performed whole-genome sequencing of DNA from 20 osteosarcoma tumor samples and matched normal tissue in a discovery cohort, as well as 14 samples in a validation cohort. Single-nucleotide variations (SNVs) exhibited a pattern of localized hypermutation called kataegis in 50% of the tumors. We identified p53 pathway lesions in all tumors in the discovery cohort, nine of which were translocations in the first intron of the TP53 gene. Beyond TP53, the RB1, ATRX, and DLG2 genes showed recurrent somatic alterations in 29%-53% of the tumors. These data highlight the power of whole-genome sequencing for identifying recurrent somatic alterations in cancer genomes that may be missed using other methods. GRCh37/hg19 Yes NA CTDB0381 Research 24703847 Chen X, Bahrami A, Pappo A, Easton J, Dalton J, Hedlund E, Ellison D, Shurtleff S, Wu G, Wei L, Parker M, Rusch M, Nagahawatte P, Wu J, Mao S, Boggs K, Mulder H, Yergeau D, Lu C, Ding L, Edmonson M, Qu C, Wang J, Li Y, Navid F, Daw NC, Mardis ER, Wilson RK, Downing JR, Zhang J, Dyer MA Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma Cell Reports 2014 Apr 6 Osteosarcoma Next Generation Sequencing Homo sapiens SJOS005_D Illumina HiSeq2000 chr10:0-9216632:0;chr10:103872717-122644322:0;chr10:104042466-103872716:1;chr10:122644323-122648107:-1;chr10:122648108-135534747:0;chr10:26001761-104042465:0;chr10:9216633-26001760:-1;chr11:0-77648050:0;chr11:111478533-46715306:1;chr11:46715307-135006516:0;chr11:77647178-80154857:0;chr11:77648051-77647177:1;chr11:80107698-81075738:0;chr11:80154858-80275358:-1;chr11:80275359-80485519:0;chr11:80485520-80107697:1;chr11:81075739-81129420:-1;chr11:81129421-92458714:0;chr11:92377198-111478532:0;chr11:92458715-92377197:1;chr12:0-20112320:0;chr12:20112321-20213817:-1;chr12:20213818-48674465:0;chr12:48509289-133851895:0;chr12:48674466-48509288:1;chr13:0-115169878:0;chr14:0-69399788:0;chr14:102547510-74126373:1;chr14:103810250-107349540:0;chr14:103914039-103810249:1;chr14:69399789-69407473:-1;chr14:69407474-102547509:0;chr14:74126374-103914038:0;chr15:0-102531392:0;chr16:0-34918017:0;chr16:34918018-34978009:-1;chr16:34978010-64857218:0;chr16:64582001-90354753:0;chr16:64855918-64902479:0;chr16:64857219-64855917:1;chr16:64902480-64582000:1;chr17:0-16375896:0;chr17:16375897-18011594:-1;chr17:17273325-18878333:-1;chr17:18878334-18878739:0;chr17:18878740-19317479:-1;chr17:19317480-54111363:0;chr17:54026770-56589967:0;chr17:54111364-54026769:1;chr17:56589968-60998711:-1;chr17:60998712-61357150:0;chr17:61357151-64604928:-1;chr17:64294589-69309758:-1;chr17:64724975-70276849:-1;chr17:64725706-69795788:-1;chr17:67931615-70130180:-1;chr17:69750320-68086989:1;chr17:70117676-70291927:-1;chr17:70276398-56608280:1;chr17:70277015-64725551:1;chr17:70291928-81195210:0;chr18:0-89840:0;chr18:107593-1280132:0;chr18:11743950-31529475:0;chr18:1280133-1284981:-1;chr18:1284982-2649087:0;chr18:14739124-14739401:0;chr18:14739402-8890496:1;chr18:22445787-11743949:1;chr18:2649088-7192738:-1;chr18:31529476-37626598:-1;chr18:32625379-33490069:-1;chr18:3292476-3399560:-1;chr18:33832275-49471250:-1;chr18:35545503-57656446:-1;chr18:38688686-42524095:-1;chr18:42578596-46919939:-1;chr18:43984462-48951389:-1;chr18:46098436-32605070:1;chr18:47142984-52478915:-1;chr18:48589284-32373156:1;chr18:50994075-51494750:-1;chr18:51529306-32439351:1;chr18:55892331-55890693:1;chr18:56371525-55892400:1;chr18:56433618-37086604:1;chr18:57656447-78077248:0;chr18:7192739-8879487:0;chr18:8879488-14739123:-1;chr18:8890497-22445786:0;chr18:89841-107592:-1;chr19:0-35534393:0;chr19:35534394-35542979:-1;chr19:35542980-38037917:0;chr19:38037918-38039502:-1;chr19:38039503-39588850:0;chr19:39588851-40328493:-1;chr19:40328494-59128983:0;chr1:0-33769775:0;chr1:151880489-151880596:-1;chr1:151880597-163798033:0;chr1:163798034-227036256:-1;chr1:166888394-228455449:-1;chr1:168430820-168432576:-1;chr1:172292879-172358942:-1;chr1:173121812-199649122:-1;chr1:189068206-189698596:-1;chr1:190925127-196235588:-1;chr1:191244522-194630146:-1;chr1:191813545-191239739:1;chr1:194630964-173121883:1;chr1:194835337-189083157:1;chr1:196241722-194875105:1;chr1:196623173-199124410:-1;chr1:198811597-199151929:-1;chr1:228455450-228458903:0;chr1:228458904-228458960:-1;chr1:228458961-249250621:0;chr1:31502598-151880488:0;chr1:33769776-31502597:1;chr20:0-50471703:0;chr20:46813649-53774698:0;chr20:50471704-50646290:-1;chr20:50506801-50780913:-1;chr20:50650557-50436091:1;chr20:50780914-51444736:0;chr20:51444737-46813648:1;chr20:53774699-54193393:-1;chr20:54193394-63025520:0;chr21:0-48129895:0;chr22:0-23823428:0;chr22:23823429-27370359:-1;chr22:27370360-33542709:0;chr22:33542710-37579658:-1;chr22:37579659-51304566:0;chr2:0-8885830:0;chr2:28648603-28983854:-1;chr2:28983855-243199373:0;chr2:8781361-28648602:0;chr2:8885831-8781360:1;chr3:0-25698973:0;chr3:102210932-110297820:-1;chr3:104492452-110466639:-1;chr3:104565079-104794305:-1;chr3:107556615-109401669:-1;chr3:110338007-106401714:1;chr3:110466640-110469446:0;chr3:110469447-111092973:-1;chr3:110924920-109031586:1;chr3:111092974-115772387:0;chr3:114837888-116200836:0;chr3:115772388-114837887:1;chr3:116200837-96530885:1;chr3:116359144-116713646:-1;chr3:116713647-174635588:0;chr3:174635589-174932044:-1;chr3:174696822-175002521:-1;chr3:175002522-198022430:0;chr3:25698974-25769958:-1;chr3:25769959-60356519:0;chr3:60356520-60543725:-1;chr3:60543726-77755667:0;chr3:77755668-77801058:-1;chr3:77801059-78234498:0;chr3:78234499-78234680:-1;chr3:78234681-86772538:0;chr3:86772258-88375342:0;chr3:86772539-86800738:-1;chr3:86800739-86973364:0;chr3:86973365-86772257:1;chr3:88375343-107555268:-1;chr3:88745291-88776082:-1;chr3:93568726-103971354:-1;chr3:95371633-102793109:-1;chr3:95372468-104686162:-1;chr3:96530886-116359143:0;chr4:0-25460357:0;chr4:110488613-110488812:-1;chr4:110488813-191154276:0;chr4:25460358-34739463:-1;chr4:27900722-35851890:0;chr4:34726065-33898223:1;chr4:34739464-35662382:0;chr4:35662383-27900721:1;chr4:35851891-35852324:-1;chr4:35852325-110488612:0;chr5:0-2438185:0;chr5:142142157-142144461:-1;chr5:142142181-142144196:-1;chr5:142142289-142144022:-1;chr5:142142341-142141829:1;chr5:142144340-142141891:1;chr5:142144672-142144363:1;chr5:142144675-142143928:1;chr5:148853572-146547549:1;chr5:151085392-147817855:1;chr5:151799493-180915260:0;chr5:2438186-4719252:-1;chr5:26114450-26115052:-1;chr5:26115053-38340195:0;chr5:3299177-26114449:0;chr5:3602022-4712879:-1;chr5:38337833-49943370:0;chr5:38340196-44915418:-1;chr5:38869781-12934923:1;chr5:43125112-43133364:-1;chr5:43772016-43775532:-1;chr5:44813112-44438711:1;chr5:44915419-45106840:0;chr5:45106841-45442178:-1;chr5:45441869-44936906:1;chr5:45442179-45444617:0;chr5:45444618-38337832:1;chr5:4719253-6481424:0;chr5:49943371-151799492:-1;chr5:6481425-3299176:1;chr6:0-38608130:0;chr6:100199725-99269715:1;chr6:100216387-163356418:-1;chr6:100217292-94734740:1;chr6:100742650-115249776:-1;chr6:100753149-67737204:1;chr6:101912029-39726789:1;chr6:101938901-47412207:1;chr6:115297694-48412613:1;chr6:115703730-63711828:1;chr6:115708418-134029455:-1;chr6:115952333-48780095:1;chr6:117448502-164597983:0;chr6:120200377-49498270:1;chr6:128890388-54672123:1;chr6:130393292-51722974:1;chr6:130442632-51677188:1;chr6:130444244-38604662:1;chr6:138340886-138341003:-1;chr6:142097319-115977936:1;chr6:142832590-70096046:1;chr6:143120119-164139302:-1;chr6:146629194-115977790:1;chr6:147228348-70127550:1;chr6:147732377-100483638:1;chr6:152844410-53912451:1;chr6:152980512-92310812:1;chr6:162672259-46475774:1;chr6:162896605-141352725:1;chr6:162970151-115294028:1;chr6:163163669-100231550:1;chr6:164139303-164141433:0;chr6:164141434-117448501:1;chr6:164597984-63961777:1;chr6:38608131-93087140:-1;chr6:38640009-38065479:1;chr6:38656591-37454228:1;chr6:39102412-39116272:-1;chr6:39146679-68678818:-1;chr6:40064307-52794754:-1;chr6:41048661-104018438:-1;chr6:43116404-43116445:-1;chr6:44665079-44475105:1;chr6:49229610-78247412:-1;chr6:49437555-51506407:-1;chr6:50536157-50518263:1;chr6:50713323-39196628:1;chr6:50845774-55100250:-1;chr6:51141839-51484091:-1;chr6:51699518-104062507:-1;chr6:52075949-40960176:1;chr6:52284374-56545165:-1;chr6:53915455-145919745:-1;chr6:54517116-143092585:-1;chr6:54650495-115145181:-1;chr6:54673348-129058297:-1;chr6:54758345-70060109:-1;chr6:54994539-147733147:-1;chr6:55197454-38499041:1;chr6:55321298-39087344:1;chr6:56547609-39099956:1;chr6:56551152-54699319:1;chr6:57040887-52480568:1;chr6:63713968-50796117:1;chr6:63961778-171115067:0;chr6:65055255-128766047:-1;chr6:65434912-100343621:-1;chr6:66265670-63965504:1;chr6:66948544-66812253:1;chr6:67715024-48338822:1;chr6:68678916-67387922:1;chr6:69621876-47262487:1;chr6:70061103-98492788:-1;chr6:70320534-49518493:1;chr6:76433696-162945893:-1;chr6:76440189-53643530:1;chr6:76673964-50714059:1;chr6:78219910-69521332:1;chr6:82386900-115866081:-1;chr6:91438710-40597145:1;chr6:91836712-67670904:1;chr6:92062901-129817339:-1;chr6:92069238-93103333:-1;chr6:92095222-115680474:-1;chr6:93285609-100764221:-1;chr6:95441473-145897239:-1;chr6:97605748-73235318:1;chr6:98235455-47464425:1;chr6:99390546-70085676:1;chr7:0-12699288:0;chr7:110067170-110071784:-1;chr7:110071785-130995713:0;chr7:12375138-29785220:0;chr7:12699289-12375137:1;chr7:130944258-146569587:0;chr7:130995714-130944257:1;chr7:146569588-146887970:-1;chr7:146887971-159138663:0;chr7:29672565-67080136:0;chr7:29785221-29672564:1;chr7:67080137-67081259:-1;chr7:67081260-69659211:0;chr7:69659212-69888024:-1;chr7:69888025-70115234:0;chr7:70115235-70192192:-1;chr7:70192193-96604494:0;chr7:96502302-110067169:0;chr7:96604495-96502301:1;chr8:0-37500195:0;chr8:118978979-118988540:-1;chr8:118988541-144295462:0;chr8:144295463-144295521:-1;chr8:144295522-146364022:0;chr8:37414576-118978978:0;chr8:37500196-37414575:1;chr9:0-9950441:0;chr9:124175825-128201630:0;chr9:124300117-124175824:1;chr9:128201631-128303929:-1;chr9:128303930-141213431:0;chr9:30816892-90880250:0;chr9:31381465-30816891:1;chr9:90880251-90884336:-1;chr9:90884337-124300116:0;chr9:9950442-9950773:-1;chr9:9950774-31381464:0;chrX:0-46048519:0;chrX:123115147-123135684:-1;chrX:123135685-155270560:0;chrX:46048520-46051710:-1;chrX:46051711-76193239:0;chrX:76193240-88508799:-1;chrX:88508800-123115146:0;chrY:0-59373566:0 hs1:150190710-150190710,hs18:35019436-35019436;hs1:163881810-163881810,hs1:163728408-163728408;hs1:165454505-165454505,hs1:166289365-166289365;hs1:166887103-166887103,hs1:163214664-163214664;hs1:178806161-178806161,hs1:203247752-203247752;hs1:187197271-187197271,hs1:187200584-187200584;hs1:188272022-188272022,hs5:42516185-42516185;hs1:189698593-189698593,hs1:192218419-192218419;hs1:192212247-192212247,hs1:195067387-195067387;hs1:192212291-192212291,hs1:191813594-191813594;hs1:194632268-194632268,hs1:191244603-191244603;hs1:195046855-195046855,hs1:199657797-199657797;hs1:195046926-195046926,hs1:156935292-156935292;hs1:210741648-210741648,hs1:233360870-233360870;hs1:219249940-219249940,hs1:227042886-227042886;hs1:231842357-231842357,hs1:235627384-235627384;hs1:233548665-233548665,hs17:70141719-70141719;hs1:247410644-247410644,hs18:29345508-29345508;hs10:4022319-4022319,hs19:39588521-39588521;hs10:4512785-4512785,hs19:38596551-38596551;hs10:4705400-4705400,hs19:33669093-33669093;hs10:4705547-4705547,hs19:33669093-33669093;hs10:4710824-4710824,hs19:33531993-33531993;hs10:5577824-5577824,hsX:75284498-75284498;hs10:9147003-9147003,hs5:38346474-38346474;hs10:29272287-29272287,hsX:50666004-50666004;hs10:42647705-42647705,hs6:48525668-48525668;hs11:2665252-2665252,hs7:67079827-67079827;hs11:3664891-3664891,hs5:149504431-149504431;hs11:34780628-34780628,hs19:39106283-39106283;hs11:35314002-35314002,hs5:42679825-42679825;hs11:43295586-43295586,hsX:76178720-76178720;hs11:43436330-43436330,hsX:82631013-82631013;hs11:46716602-46716602,hs20:56104016-56104016;hs11:51345040-51345040,hs18:9850983-9850983;hs11:59889695-59889695,hs11:59892399-59892399;hs11:111476706-111476706,hs20:56119259-56119259;hs11:111658893-111658893,hs19:31954747-31954747;hs11:112733841-112733841,hs5:42716402-42716402;hs11:123147417-123147417,hs5:42606530-42606530;hs12:20606292-20606292,hs12:20720032-20720032;hs12:21962087-21962087,hs12:40089430-40089430;hs13:101756771-101756771,hs5:142141854-142141854;hs13:101833542-101833542,hs5:142142329-142142329;hs14:29668039-29668039,hs19:18710137-18710137;hs16:9802350-9802350,hs9:23292351-23292351;hs17:7528965-7528965,hs19:3798149-3798149;hs17:15938135-15938135,hs17:18011928-18011928;hs17:16720785-16720785,hs6:55436886-55436886;hs17:16737680-16737680,hs6:52232094-52232094;hs17:17273199-17273199,hs17:21197540-21197540;hs17:18882877-18882877,hs17:21243160-21243160;hs17:19317893-19317893,hs6:52231489-52231489;hs17:19641279-19641279,hs17:18882239-18882239;hs17:19641678-19641678,hs3:88623684-88623684;hs17:20016250-20016250,hs6:49222533-49222533;hs17:20025180-20025180,hs6:141285336-141285336;hs17:20108850-20108850,hs6:67381065-67381065;hs17:20121301-20121301,hs6:92093945-92093945;hs17:20151494-20151494,hs6:82382910-82382910;hs17:20198196-20198196,hs3:114942934-114942934;hs17:20213325-20213325,hs6:164636697-164636697;hs17:20234836-20234836,hs3:115387071-115387071;hs17:20302947-20302947,hs3:109135004-109135004;hs17:20323023-20323023,hs3:116164737-116164737;hs17:20323937-20323937,hs6:146553052-146553052;hs17:20406333-20406333,hs17:16375317-16375317;hs17:20778082-20778082,hs6:53053612-53053612;hs17:21198692-21198692,hs3:81862790-81862790;hs17:21892825-21892825,hs6:53515449-53515449;hs17:54073198-54073198,hs20:55124362-55124362;hs17:62523869-62523869,hs17:64793365-64793365;hs17:68521284-68521284,hs17:70134331-70134331;hs17:69270699-69270699,hs1:233490865-233490865;hs17:69433273-69433273,hs17:64785229-64785229;hs18:3154588-3154588,hs19:34131463-34131463;hs18:3405730-3405730,hs18:3408411-3408411;hs18:14739034-14739034,hs18:8879196-8879196;hs18:18518082-18518082,hs1:245783942-245783942;hs18:22612423-22612423,hs5:149294807-149294807;hs18:31666592-31666592,hs18:32405421-32405421;hs18:32449506-32449506,hs18:39574625-39574625;hs18:32985216-32985216,hs18:35348639-35348639;hs18:35092604-35092604,hs18:39908351-39908351;hs18:35544072-35544072,hs18:31596945-31596945;hs18:37230115-37230115,hs18:39909527-39909527;hs18:37652687-37652687,hs18:45699461-45699461;hs18:39434117-39434117,hs18:33743598-33743598;hs18:42883830-42883830,hs18:44956295-44956295;hs18:44363761-44363761,hs18:36470333-36470333;hs18:44378204-44378204,hs18:54184229-54184229;hs18:45245357-45245357,hs18:52235819-52235819;hs18:45674634-45674634,hs18:44851278-44851278;hs18:48414856-48414856,hs18:46083037-46083037;hs18:48651466-48651466,hs18:46632420-46632420;hs18:48988291-48988291,hs18:48867310-48867310;hs18:49505527-49505527,hs18:43893500-43893500;hs18:54152328-54152328,hs18:52221527-52221527;hs18:55891623-55891623,hs18:49817805-49817805;hs19:28789298-28789298,hs20:56119229-56119229;hs19:28796467-28796467,hs11:111478101-111478101;hs19:30269696-30269696,hs19:30267500-30267500;hs19:31091975-31091975,hs19:38003187-38003187;hs19:31153758-31153758,hs19:31136344-31136344;hs19:31945533-31945533,hs18:3208490-3208490;hs19:33180898-33180898,hs11:111955173-111955173;hs19:33397936-33397936,hs11:56934651-56934651;hs19:33642748-33642748,hs19:33670424-33670424;hs19:34131228-34131228,hs19:34129650-34129650;hs19:34769700-34769700,hs10:26278126-26278126;hs19:35605840-35605840,hs10:26929870-26929870;hs19:37936796-37936796,hs11:42265423-42265423;hs19:38036045-38036045,hs19:38039726-38039726;hs19:38066180-38066180,hs19:38088122-38088122;hs19:38091283-38091283,hs19:38086657-38086657;hs19:38092895-38092895,hs10:4709411-4709411;hs19:39064765-39064765,hs10:4685144-4685144;hs19:39103288-39103288,hs20:54283229-54283229;hs19:40338411-40338411,hs10:3449527-3449527;hs2:36972909-36972909,hs2:37127060-37127060;hs2:37124956-37124956,hs3:88744885-88744885;hs2:37126877-37126877,hs2:34740239-34740239;hs2:37143155-37143155,hs2:36945789-36945789;hs2:43369928-43369928,hs2:134431164-134431164;hs2:119941622-119941622,hs19:34775217-34775217;hs2:136514803-136514803,hs2:136523513-136523513;hs2:136530189-136530189,hs2:136517499-136517499;hs2:147332931-147332931,hs15:58344688-58344688;hs20:42067072-42067072,hs20:42066337-42066337;hs20:54276167-54276167,hs19:30685244-30685244;hs20:54283591-54283591,hs19:38049856-38049856;hs20:54283916-54283916,hs19:38032005-38032005;hs20:54352709-54352709,hs19:33647070-33647070;hs20:55446643-55446643,hs5:89515282-89515282;hs20:57468181-57468181,hs5:38174651-38174651;hs21:9847808-9847808,hs5:4479373-4479373;hs22:33936154-33936154,hs22:37594497-37594497;hs3:78719089-78719089,hs6:51014576-51014576;hs3:81140725-81140725,hs6:47455526-47455526;hs3:81853229-81853229,hs6:91939958-91939958;hs3:82024081-82024081,hs3:109402125-109402125;hs3:82072234-82072234,hs6:128767566-128767566;hs3:82575269-82575269,hs6:53968190-53968190;hs3:85297377-85297377,hs6:41634402-41634402;hs3:86800517-86800517,hs3:86772561-86772561;hs3:88243024-88243024,hs6:96843432-96843432;hs3:88346093-88346093,hs6:145925892-145925892;hs3:88397748-88397748,hs3:115703772-115703772;hs3:88809861-88809861,hs6:41634776-41634776;hs3:89391164-89391164,hs3:111022410-111022410;hs3:89422450-89422450,hs6:58464754-58464754;hs3:94885463-94885463,hs6:77277195-77277195;hs3:96427986-96427986,hs6:64048116-64048116;hs3:96519958-96519958,hs3:102797816-102797816;hs3:96528020-96528020,hs6:163323954-163323954;hs3:96533912-96533912,hs3:115707500-115707500;hs3:97610238-97610238,hs6:92063103-92063103;hs3:101373650-101373650,hs6:48376414-48376414;hs3:103413468-103413468,hs6:47316058-47316058;hs3:103414302-103414302,hs6:163357643-163357643;hs3:103653429-103653429,hs6:79289208-79289208;hs3:104200230-104200230,hs6:93355969-93355969;hs3:104371960-104371960,hs3:110952352-110952352;hs3:104586475-104586475,hs6:128919574-128919574;hs3:104675836-104675836,hs3:95371690-95371690;hs3:104683982-104683982,hs6:53649584-53649584;hs3:104691212-104691212,hs3:104797915-104797915;hs3:104820590-104820590,hs6:164145669-164145669;hs3:104847783-104847783,hs17:20197059-20197059;hs3:104855930-104855930,hs6:115665429-115665429;hs3:105610148-105610148,hs6:55102576-55102576;hs3:106155127-106155127,hs3:102797657-102797657;hs3:106157094-106157094,hs3:104413752-104413752;hs3:106318220-106318220,hs6:164584312-164584312;hs3:106402026-106402026,hs6:93050688-93050688;hs3:107563792-107563792,hs6:165143413-165143413;hs3:108257924-108257924,hs6:77279048-77279048;hs3:108285698-108285698,hs3:116158111-116158111;hs3:108932398-108932398,hs6:100369527-100369527;hs3:108938508-108938508,hs6:141676991-141676991;hs3:109119957-109119957,hs6:93355776-93355776;hs3:109136112-109136112,hs6:91939296-91939296;hs3:109279866-109279866,hs3:109390241-109390241;hs3:109449409-109449409,hs6:142818716-142818716;hs3:110217610-110217610,hs6:134101259-134101259;hs3:110341345-110341345,hs6:46479441-46479441;hs3:110538414-110538414,hs6:116550847-116550847;hs3:110928462-110928462,hs3:104369586-104369586;hs3:111069908-111069908,hs6:147845762-147845762;hs3:114839049-114839049,hs6:48780540-48780540;hs3:115010234-115010234,hs6:145926656-145926656;hs3:115316343-115316343,hs3:97313792-97313792;hs3:115360504-115360504,hs6:90583822-90583822;hs3:115447337-115447337,hs3:109447807-109447807;hs3:115633230-115633230,hs6:49620713-49620713;hs3:115775163-115775163,hs3:115665645-115665645;hs3:115775304-115775304,hs6:47297620-47297620;hs3:115776126-115776126,hs11:16705910-16705910;hs3:115784754-115784754,hs6:142818537-142818537;hs3:115979614-115979614,hs6:164668037-164668037;hs3:116086883-116086883,hs6:91875736-91875736;hs3:116181674-116181674,hs3:115370369-115370369;hs3:116198239-116198239,hs3:104495551-104495551;hs4:23710780-23710780,hs5:4713797-4713797;hs4:25473680-25473680,hs4:34668872-34668872;hs4:25491133-25491133,hs4:35825994-35825994;hs4:26141830-26141830,hs5:3427033-3427033;hs4:28604057-28604057,hs5:4840952-4840952;hs4:33898648-33898648,hs5:2437709-2437709;hs4:33926250-33926250,hs21:9846660-9846660;hs4:33926474-33926474,hs5:2530829-2530829;hs4:34717553-34717553,hs5:3426047-3426047;hs4:34725481-34725481,hs4:23711285-23711285;hs4:34726048-34726048,hs5:3426692-3426692;hs4:34741458-34741458,hs4:35846832-35846832;hs4:35536472-35536472,hs5:3610318-3610318;hs4:35547699-35547699,hs4:34192089-34192089;hs4:35824972-35824972,hs4:34717047-34717047;hs4:35836735-35836735,hs4:34725315-34725315;hs4:35846739-35846739,hs4:26141665-26141665;hs4:47767479-47767479,hs18:61679763-61679763;hs4:67780309-67780309,hs4:71839720-71839720;hs4:71839236-71839236,hs4:67779935-67779935;hs4:150719562-150719562,hs12:18886678-18886678;hs4:151118315-151118315,hs2:147251981-147251981;hs5:2534013-2534013,hs4:35722870-35722870;hs5:2540042-2540042,hs4:23709871-23709871;hs5:3239065-3239065,hs5:3276466-3276466;hs5:3253575-3253575,hs5:3238540-3238540;hs5:3426205-3426205,hs4:25472937-25472937;hs5:3433879-3433879,hs4:25459740-25459740;hs5:3434193-3434193,hs5:4069369-4069369;hs5:3601184-3601184,hs4:25490623-25490623;hs5:3609882-3609882,hs4:23692914-23692914;hs5:4687625-4687625,hs5:2539588-2539588;hs5:4721235-4721235,hs4:35662251-35662251;hs5:18483034-18483034,hs1:176464601-176464601;hs5:24619955-24619955,hs5:26132797-26132797;hs5:33290691-33290691,hs5:24361220-24361220;hs5:38342044-38342044,hs5:44900370-44900370;hs5:38699260-38699260,hsX:77265842-77265842;hs5:40793517-40793517,hs5:40782340-40782340;hs5:40820308-40820308,hs1:168326477-168326477;hs5:42508883-42508883,hs19:30270886-30270886;hs5:42619203-42619203,hs19:39078927-39078927;hs5:43133794-43133794,hs20:53727351-53727351;hs5:43684269-43684269,hs5:43836208-43836208;hs5:43997956-43997956,hs5:45034426-45034426;hs5:44814154-44814154,hs5:44812309-44812309;hs5:44814434-44814434,hs5:44926769-44926769;hs5:44887441-44887441,hs5:38315319-38315319;hs5:45104960-45104960,hs10:9209409-9209409;hs5:45433047-45433047,hs5:38341512-38341512;hs5:95211458-95211458,hs20:55443378-55443378;hs5:142142152-142142152,hs5:142144432-142144432;hs5:142142225-142142225,hs5:142144926-142144926;hs5:142142353-142142353,hs5:142148949-142148949;hs5:142144029-142144029,hs5:142142155-142142155;hs5:142144245-142144245,hs5:142141890-142141890;hs5:142144324-142144324,hs5:142141944-142141944;hs5:142144519-142144519,hs7:67079855-67079855;hs5:142144627-142144627,hs13:105357688-105357688;hs5:142144907-142144907,hs7:67079827-67079827;hs5:142929510-142929510,hs5:147525705-147525705;hs5:144153562-144153562,hs18:22611588-22611588;hs5:147044759-147044759,hs5:144251324-144251324;hs5:148380981-148380981,hs7:69591061-69591061;hs5:148394337-148394337,hs5:10737274-10737274;hs5:148855115-148855115,hs5:146552939-146552939;hs5:149066651-149066651,hs11:4142770-4142770;hs5:149080385-149080385,hs11:3237720-3237720;hs5:149522221-149522221,hs5:141732537-141732537;hs5:151735766-151735766,hs18:12218080-12218080;hs5:152053296-152053296,hs7:70280126-70280126;hs6:36800437-36800437,hs17:15099460-15099460;hs6:36800441-36800441,hs17:7741515-7741515;hs6:37454525-37454525,hs17:20008259-20008259;hs6:38639302-38639302,hs3:77507076-77507076;hs6:38639451-38639451,hs6:38630515-38630515;hs6:39103717-39103717,hs6:134056581-134056581;hs6:39198690-39198690,hs6:143093723-143093723;hs6:39359983-39359983,hs6:40503935-40503935;hs6:39784524-39784524,hs6:100486714-100486714;hs6:39784741-39784741,hs3:88372342-88372342;hs6:39786991-39786991,hs17:20175728-20175728;hs6:40588050-40588050,hs3:115956677-115956677;hs6:40591956-40591956,hs3:115781214-115781214;hs6:41633575-41633575,hs6:44611752-44611752;hs6:44611645-44611645,hs6:44611097-44611097;hs6:44624840-44624840,hs3:78923597-78923597;hs6:46339634-46339634,hs6:120819144-120819144;hs6:46386032-46386032,hs17:20324614-20324614;hs6:46581572-46581572,hs3:115771661-115771661;hs6:47248872-47248872,hs3:109355778-109355778;hs6:47263750-47263750,hs3:104564021-104564021;hs6:47318318-47318318,hs6:93087861-93087861;hs6:47326690-47326690,hs3:88367764-88367764;hs6:47437775-47437775,hs3:88437119-88437119;hs6:47464960-47464960,hs3:82341397-82341397;hs6:47618236-47618236,hs6:51830033-51830033;hs6:47650483-47650483,hs6:93189998-93189998;hs6:48100515-48100515,hs3:107563894-107563894;hs6:48340514-48340514,hs6:73239723-73239723;hs6:48362261-48362261,hs6:93103432-93103432;hs6:49137714-49137714,hs6:47248006-47248006;hs6:49137846-49137846,hs3:82330595-82330595;hs6:49519674-49519674,hs6:67742139-67742139;hs6:49523553-49523553,hs3:109119243-109119243;hs6:50798374-50798374,hs6:145921293-145921293;hs6:51613120-51613120,hs6:54134412-54134412;hs6:51682854-51682854,hs6:100672705-100672705;hs6:51691352-51691352,hs6:95008341-95008341;hs6:51694760-51694760,hs6:56470181-56470181;hs6:51724084-51724084,hs3:110336236-110336236;hs6:51774091-51774091,hs3:82562467-82562467;hs6:51776503-51776503,hs6:91604145-91604145;hs6:51829457-51829457,hs6:48458508-48458508;hs6:51877513-51877513,hs17:20291996-20291996;hs6:53948929-53948929,hs3:81051084-81051084;hs6:54091051-54091051,hs6:51907759-51907759;hs6:54094055-54094055,hs3:116042095-116042095;hs6:54432804-54432804,hs3:101216088-101216088;hs6:54551769-54551769,hs3:81853040-81853040;hs6:54702224-54702224,hs17:17670162-17670162;hs6:54874749-54874749,hs6:47650158-47650158;hs6:55180557-55180557,hs6:41350044-41350044;hs6:56757370-56757370,hs6:51593846-51593846;hs6:56774640-56774640,hs3:87877386-87877386;hs6:58465762-58465762,hs3:106315256-106315256;hs6:63966856-63966856,hs6:70087555-70087555;hs6:64053541-64053541,hs6:100289049-100289049;hs6:65052096-65052096,hs3:109277769-109277769;hs6:65431272-65431272,hs6:54755644-54755644;hs6:66276930-66276930,hs6:72762278-72762278;hs6:66946826-66946826,hs6:54274207-54274207;hs6:67711025-67711025,hs6:115668343-115668343;hs6:68472373-68472373,hs6:129202113-129202113;hs6:69378778-69378778,hs6:102446299-102446299;hs6:69629269-69629269,hs6:147273752-147273752;hs6:70096520-70096520,hs6:162462462-162462462;hs6:70129406-70129406,hs3:96526929-96526929;hs6:70319958-70319958,hs3:116164445-116164445;hs6:77293612-77293612,hs3:104803319-104803319;hs6:77331879-77331879,hs3:103649013-103649013;hs6:90543085-90543085,hs3:97793169-97793169;hs6:91509208-91509208,hs6:100506929-100506929;hs6:91836212-91836212,hs6:48358897-48358897;hs6:92316179-92316179,hs3:109630558-109630558;hs6:92995101-92995101,hs3:110536301-110536301;hs6:93102510-93102510,hs3:103312179-103312179;hs6:93131260-93131260,hs6:53959328-53959328;hs6:93189734-93189734,hs6:47615976-47615976;hs6:93241864-93241864,hs6:164562817-164562817;hs6:93284370-93284370,hs6:48082590-48082590;hs6:93296310-93296310,hs3:115782853-115782853;hs6:93297515-93297515,hs3:115372064-115372064;hs6:94736395-94736395,hs3:102176164-102176164;hs6:95011400-95011400,hs6:98217807-98217807;hs6:96295903-96295903,hs6:91508856-91508856;hs6:96296800-96296800,hs17:15937596-15937596;hs6:97954601-97954601,hs6:86987744-86987744;hs6:97955392-97955392,hs3:105608653-105608653;hs6:98217048-98217048,hs3:104674773-104674773;hs6:98493688-98493688,hs6:120623816-120623816;hs6:99414817-99414817,hs3:108257718-108257718;hs6:99414958-99414958,hs17:20211390-20211390;hs6:100191483-100191483,hs6:72715835-72715835;hs6:100191668-100191668,hs3:101206903-101206903;hs6:100196970-100196970,hs6:46580417-46580417;hs6:100216454-100216454,hs3:81327740-81327740;hs6:100289632-100289632,hs3:115679827-115679827;hs6:100435852-100435852,hs17:21242364-21242364;hs6:100437556-100437556,hs6:141300827-141300827;hs6:100765341-100765341,hs3:115370091-115370091;hs6:101932965-101932965,hs3:110522765-110522765;hs6:101938737-101938737,hs3:116162966-116162966;hs6:102347343-102347343,hs6:115447219-115447219;hs6:102445371-102445371,hs6:67708062-67708062;hs6:104019973-104019973,hs6:115154416-115154416;hs6:104991864-104991864,hs3:110949152-110949152;hs6:105870555-105870555,hs6:130419671-130419671;hs6:115229619-115229619,hs6:164585204-164585204;hs6:115536203-115536203,hs6:51698376-51698376;hs6:115681547-115681547,hs6:163193824-163193824;hs6:115705712-115705712,hs3:110339374-110339374;hs6:115951256-115951256,hs6:105566941-105566941;hs6:120213779-120213779,hs3:104582711-104582711;hs6:120363019-120363019,hs3:81138926-81138926;hs6:120623577-120623577,hs3:96519236-96519236;hs6:128917764-128917764,hs6:92598439-92598439;hs6:129058812-129058812,hs3:110486368-110486368;hs6:129818521-129818521,hs3:116204484-116204484;hs6:130393023-130393023,hs6:128889934-128889934;hs6:130416525-130416525,hs6:77424111-77424111;hs6:130441144-130441144,hs6:78218004-78218004;hs6:141300745-141300745,hs6:142149676-142149676;hs6:141675033-141675033,hs6:95450340-95450340;hs6:142095386-142095386,hs3:115961575-115961575;hs6:143084328-143084328,hs6:129198077-129198077;hs6:143660788-143660788,hs3:88353109-88353109;hs6:146598085-146598085,hs6:95440559-95440559;hs6:146786789-146786789,hs3:82021536-82021536;hs6:147267338-147267338,hs3:108938230-108938230;hs6:147276987-147276987,hs6:100740859-100740859;hs6:147280119-147280119,hs3:101328050-101328050;hs6:152842684-152842684,hs6:79288846-79288846;hs6:162461819-162461819,hs6:115152661-115152661;hs6:162671804-162671804,hs6:49228357-49228357;hs6:162892651-162892651,hs3:115781013-115781013;hs6:162946180-162946180,hs3:115495272-115495272;hs6:162968811-162968811,hs6:76437937-76437937;hs6:163192364-163192364,hs17:20230378-20230378;hs6:163323076-163323076,hs17:20148470-20148470;hs6:164381166-164381166,hs6:77330190-77330190;hs6:164564935-164564935,hs6:50838716-50838716;hs6:164597701-164597701,hs6:130499336-130499336;hs6:164633177-164633177,hs3:89300320-89300320;hs6:164666378-164666378,hs6:134052920-134052920;hs6:164682345-164682345,hs6:68326567-68326567;hs6:164683916-164683916,hs3:115005995-115005995;hs7:25589163-25589163,hs1:78692313-78692313;hs7:67079941-67079941,hs5:142141901-142141901;hs7:67080109-67080109,hs5:142144452-142144452;hs7:67080127-67080127,hs5:142142093-142142093;hs7:67081362-67081362,hs5:142144277-142144277;hs7:69265901-69265901,hs5:142041976-142041976;hs9:8685021-8685021,hs17:35349332-35349332;hsX:44850174-44850174,hs19:33180639-33180639;hsX:46075925-46075925,hs5:95249808-95249808;hsX:46629590-46629590,hs5:93773459-93773459;hsX:56270198-56270198,hs18:8827898-8827898;hsX:83811712-83811712,hs20:56895381-56895381;hsX:84365945-84365945,hs19:28789883-28789883;hsX:84372600-84372600,hs11:48783544-48783544;hsX:84373278-84373278,hs11:111475907-111475907 Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA Pediatric osteosarcoma is characterized by multiple somatic chromosomal lesions, including structural variations (SVs) and copy number alterations (CNAs). To define the landscape of somatic mutations in pediatric osteosarcoma, we performed whole-genome sequencing of DNA from 20 osteosarcoma tumor samples and matched normal tissue in a discovery cohort, as well as 14 samples in a validation cohort. Single-nucleotide variations (SNVs) exhibited a pattern of localized hypermutation called kataegis in 50% of the tumors. We identified p53 pathway lesions in all tumors in the discovery cohort, nine of which were translocations in the first intron of the TP53 gene. Beyond TP53, the RB1, ATRX, and DLG2 genes showed recurrent somatic alterations in 29%-53% of the tumors. These data highlight the power of whole-genome sequencing for identifying recurrent somatic alterations in cancer genomes that may be missed using other methods. GRCh37/hg19 Yes NA CTDB0382 Research 24703847 Chen X, Bahrami A, Pappo A, Easton J, Dalton J, Hedlund E, Ellison D, Shurtleff S, Wu G, Wei L, Parker M, Rusch M, Nagahawatte P, Wu J, Mao S, Boggs K, Mulder H, Yergeau D, Lu C, Ding L, Edmonson M, Qu C, Wang J, Li Y, Navid F, Daw NC, Mardis ER, Wilson RK, Downing JR, Zhang J, Dyer MA Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma Cell Reports 2014 Apr 13 Osteosarcoma Next Generation Sequencing Homo sapiens SJOS010_M Illumina HiSeq2000 chr10:0-135534747:0;chr11:0-28247999:0;chr11:28245810-39497467:0;chr11:28248000-28245809:1;chr11:39497468-39685014:-1;chr11:39685015-41794086:0;chr11:41296867-55136808:0;chr11:41794087-41296866:1;chr11:41798581-135006516:0;chr11:55136809-41798580:1;chr12:0-20662254:0;chr12:131369056-133851895:0;chr12:131484945-131369055:1;chr12:20653713-72006794:0;chr12:20662255-20653712:1;chr12:69634695-131484944:0;chr12:72006795-69634694:1;chr13:0-19215482:0;chr13:106965240-49557801:1;chr13:19215483-52510508:-1;chr13:28444154-28448736:-1;chr13:39836916-35909205:1;chr13:48521969-48694370:-1;chr13:48821858-81886196:-1;chr13:49557802-115169878:0;chr13:52688622-94067968:-1;chr13:58114809-74559322:-1;chr13:64218376-74836218:-1;chr13:65673345-28695848:1;chr13:75132067-89776862:-1;chr13:80923519-80238750:1;chr13:81774961-81776181:-1;chr13:81776365-22290156:1;chr13:81985462-106965239:0;chr13:83921635-52669030:1;chr13:85361179-20632251:1;chr13:85535127-58613270:1;chr13:85822319-87024488:-1;chr13:85972564-49092130:1;chr13:86129602-85393539:1;chr13:86247965-91125223:-1;chr13:88019043-58045876:1;chr13:90119456-92164088:-1;chr13:92725882-21633074:1;chr13:94067969-98626434:0;chr13:98626435-98653083:-1;chr13:98653084-98742737:0;chr13:98742738-81985461:1;chr14:0-22967018:0;chr14:22967019-23054195:-1;chr14:23054196-23583618:0;chr14:23583619-23620652:-1;chr14:23620653-26087493:0;chr14:26087494-26101134:-1;chr14:26101135-27562176:0;chr14:27535621-62189818:0;chr14:27562177-27535620:1;chr14:59732099-79317733:0;chr14:62189819-59732098:1;chr14:79317734-79331162:-1;chr14:79331163-107349540:0;chr15:0-25965230:0;chr15:25965231-25974268:-1;chr15:25974269-48697381:0;chr15:48680474-51703010:0;chr15:48697382-48697422:-1;chr15:48697423-48734409:0;chr15:48734410-48680473:1;chr15:51543245-102531392:0;chr15:51703011-51543244:1;chr16:0-72320862:0;chr16:72320863-72472646:-1;chr16:72470062-90354753:0;chr16:72472647-72473026:0;chr16:72473027-72470061:1;chr17:0-70523176:0;chr17:70523177-70527932:-1;chr17:70527933-81195210:0;chr18:0-42987755:0;chr18:42987756-54014653:-1;chr18:45792335-49276482:-1;chr18:54014654-78077248:0;chr19:0-6199452:0;chr19:15464441-11270949:1;chr19:22529780-22620446:-1;chr19:30317754-31251894:-1;chr19:32058559-30799855:1;chr19:32259558-32277769:-1;chr19:32699645-35378705:0;chr19:33911341-37629249:0;chr19:35378706-33911340:1;chr19:37629250-48403210:-1;chr19:42152218-42019073:1;chr19:47608949-47606063:1;chr19:48403211-48403368:0;chr19:48403369-48404383:-1;chr19:48404384-59128983:0;chr19:6199453-7500855:-1;chr19:7500856-7673951:0;chr19:7673952-32699644:-1;chr1:0-2367899:0;chr1:100681094-77657086:1;chr1:101239849-110561159:0;chr1:110308988-113940912:0;chr1:110561160-110308987:1;chr1:113940913-61907266:1;chr1:172939395-245921999:0;chr1:21415206-45531246:0;chr1:21643964-21415205:1;chr1:2367900-2368044:-1;chr1:2368045-21643963:0;chr1:236894435-172939394:1;chr1:245922000-246031775:-1;chr1:246031776-249250621:0;chr1:45531247-45954407:-1;chr1:45954408-46152522:0;chr1:46152523-52592533:-1;chr1:52592534-54371769:0;chr1:54371770-54372852:-1;chr1:54372853-56025433:0;chr1:55932223-72091843:0;chr1:56025434-55932222:1;chr1:61907267-236894434:0;chr1:72091844-72093468:-1;chr1:72093469-72094145:0;chr1:72094146-72175951:-1;chr1:72175952-73762555:0;chr1:73762556-80322822:-1;chr1:75493772-75497808:-1;chr1:75503152-75623561:-1;chr1:76214061-96074303:-1;chr1:77657032-80322828:-1;chr1:85890860-86012845:-1;chr1:90488001-101239848:-1;chr20:0-63025520:0;chr21:0-39747629:0;chr21:39747102-39795901:0;chr21:39747630-39747820:-1;chr21:39747821-39778586:0;chr21:39778587-39747101:1;chr21:39795902-39799369:-1;chr21:39799370-48129895:0;chr22:0-22072135:0;chr22:22072136-28297628:-1;chr22:28297629-31904645:0;chr22:31904646-35794906:-1;chr22:31927485-51304566:0;chr22:31928752-31954921:-1;chr22:35794907-35798394:0;chr22:35798395-31927484:1;chr2:0-72894279:0;chr2:189933143-206644875:0;chr2:190470997-189933142:1;chr2:206435384-235335006:0;chr2:206644876-206435383:1;chr2:234451810-238247431:0;chr2:235335007-234451809:1;chr2:238072799-243199373:0;chr2:238247432-238072798:1;chr2:72894280-75978227:-1;chr2:75978228-190470996:0;chr3:0-64519341:0;chr3:116387467-116976044:-1;chr3:116613540-116655954:-1;chr3:116617030-116810387:-1;chr3:116976045-171811540:0;chr3:169934631-174711856:0;chr3:171811541-169934630:1;chr3:174711857-174878817:-1;chr3:174878818-198022430:0;chr3:64205025-116387466:0;chr3:64519342-64205024:1;chr4:0-24194131:0;chr4:170926622-170927170:-1;chr4:170927171-175287812:0;chr4:171916558-191154276:0;chr4:175287813-171916557:1;chr4:24194132-24200107:-1;chr4:24200108-41728909:0;chr4:41728910-41729992:-1;chr4:41729993-44701183:0;chr4:44700623-64075439:0;chr4:44701184-44700622:1;chr4:64075440-64076006:-1;chr4:64076007-79156001:0;chr4:79156002-79158859:-1;chr4:79158860-170926621:0;chr5:0-31285432:0;chr5:101436358-122098634:0;chr5:121972473-147337692:0;chr5:122098635-121972472:1;chr5:147246604-159471138:0;chr5:147337693-147246603:1;chr5:159471139-170299667:-1;chr5:170299668-180915260:0;chr5:31285433-35927486:-1;chr5:35927487-76349976:0;chr5:76349977-101436357:-1;chr5:99400881-99715013:-1;chr6:0-44121520:0;chr6:101799447-101852542:-1;chr6:101852543-111969525:0;chr6:111962485-121699876:0;chr6:111967765-122423310:0;chr6:111969526-111962484:1;chr6:121699049-171115067:0;chr6:121699877-111967764:1;chr6:122423311-121699048:1;chr6:44121521-44816428:-1;chr6:44122426-44816629:-1;chr6:44605330-45306131:-1;chr6:44816619-44122409:1;chr6:45306132-48987179:0;chr6:48987069-101799446:0;chr6:48987180-48987068:1;chr7:0-11089861:0;chr7:11089862-11303085:-1;chr7:11303086-19177787:0;chr7:127907202-133451639:0;chr7:128055106-146808222:0;chr7:132114200-127907201:1;chr7:133451640-128055105:1;chr7:146808223-147054475:-1;chr7:146862199-147014075:-1;chr7:147054476-159138663:0;chr7:16565339-68987461:0;chr7:19177788-16565338:1;chr7:68987462-77939295:-1;chr7:69021666-68619191:1;chr7:69271312-68680356:1;chr7:77637964-78181654:0;chr7:77939296-78051787:0;chr7:78051788-77637963:1;chr7:78181655-78238901:-1;chr7:78238902-78404179:0;chr7:78404180-78421198:-1;chr7:78421199-132114199:0;chr8:0-38626537:0;chr8:100109761-111944605:0;chr8:111944606-137486195:-1;chr8:136043899-132457079:1;chr8:137486196-146364022:0;chr8:38432539-67353049:0;chr8:38626538-38432538:1;chr8:67315457-98896327:0;chr8:67353050-67315456:1;chr8:98293233-99981824:0;chr8:98896328-98293232:1;chr8:99981825-100109760:-1;chr9:0-29765785:0;chr9:130255826-137580561:0;chr9:130398732-130255825:1;chr9:137305285-141213431:0;chr9:137580562-137305284:1;chr9:29445595-130398731:0;chr9:29765786-29445594:1;chrX:0-32232425:0;chrX:133866272-155270560:0;chrX:133899531-133866271:1;chrX:32232426-32266085:-1;chrX:32266086-133899530:0;chrY:0-59373566:0 hs1:12395198-12395198,hs18:30002277-30002277;hs1:12406960-12406960,hs13:111768808-111768808;hs1:19423758-19423758,hs1:19180010-19180010;hs1:50948535-50948535,hs18:47138598-47138598;hs1:52627237-52627237,hs18:47137469-47137469;hs1:52630240-52630240,hs1:50948571-50948571;hs1:53078040-53078040,hs1:103229916-103229916;hs1:54830018-54830018,hs7:132158493-132158493;hs1:54830126-54830126,hs7:133451737-133451737;hs1:56841419-56841419,hs1:56860001-56860001;hs1:58906784-58906784,hs13:65026383-65026383;hs1:61998243-61998243,hs2:73006059-73006059;hs1:62189156-62189156,hs2:77113657-77113657;hs1:64262435-64262435,hs1:72594033-72594033;hs1:64712605-64712605,hs2:73006130-73006130;hs1:72574697-72574697,hs1:71517342-71517342;hs1:80344248-80344248,hs1:83496285-83496285;hs1:86863186-86863186,hs1:104870143-104870143;hs1:88510505-88510505,hs1:101342228-101342228;hs1:97989111-97989111,hs1:73020543-73020543;hs1:102898227-102898227,hs1:53075559-53075559;hs1:111276668-111276668,hs1:113695211-113695211;hs1:116368047-116368047,hs1:87367412-87367412;hs1:160161271-160161271,hs1:207481988-207481988;hs1:215260439-215260439,hs1:165331101-165331101;hs1:220644583-220644583,hs1:157575932-157575932;hs10:53734900-53734900,hs10:53723803-53723803;hs10:75111697-75111697,hs5:43105607-43105607;hs11:35028377-35028377,hs21:39605109-39605109;hs11:41285058-41285058,hs11:41802354-41802354;hs11:41296308-41296308,hs11:56227364-56227364;hs11:43645154-43645154,hs11:41802453-41802453;hs11:49976327-49976327,hs19:8796504-8796504;hs11:56993191-56993191,hs19:35814311-35814311;hs11:80299153-80299153,hs11:78834690-78834690;hs11:80300441-80300441,hs11:80298718-80298718;hs13:21765996-21765996,hs18:52925487-52925487;hs13:22321404-22321404,hs18:58725396-58725396;hs13:25223755-25223755,hs18:49324537-49324537;hs13:27983838-27983838,hs9:134112924-134112924;hs13:28448967-28448967,hs13:28448605-28448605;hs13:28945030-28945030,hs13:86665988-86665988;hs13:28948974-28948974,hs19:30380157-30380157;hs13:31211134-31211134,hs13:64952646-64952646;hs13:31215848-31215848,hs19:32662497-32662497;hs13:31790759-31790759,hs19:33000099-33000099;hs13:31795164-31795164,hs13:27598494-27598494;hs13:31834753-31834753,hs19:30965357-30965357;hs13:32482042-32482042,hs19:3296269-3296269;hs13:36986453-36986453,hs1:56844095-56844095;hs13:48807936-48807936,hs19:30195445-30195445;hs13:49814509-49814509,hs18:41876898-41876898;hs13:52541725-52541725,hs13:105440332-105440332;hs13:52586233-52586233,hs19:6435447-6435447;hs13:52712037-52712037,hs19:22462295-22462295;hs13:57666539-57666539,hs13:90518954-90518954;hs13:57748553-57748553,hs13:85218067-85218067;hs13:65717353-65717353,hs1:51707032-51707032;hs13:74062968-74062968,hs18:46412116-46412116;hs13:74571862-74571862,hs18:41850604-41850604;hs13:77132984-77132984,hs13:91454362-91454362;hs13:80852765-80852765,hs13:81367581-81367581;hs13:81969455-81969455,hs18:52561149-52561149;hs13:82039783-82039783,hs18:41961145-41961145;hs13:82127638-82127638,hs19:32250759-32250759;hs13:83887524-83887524,hs13:92625862-92625862;hs13:85210058-85210058,hs13:76785648-76785648;hs13:85401082-85401082,hs13:88970699-88970699;hs13:85551423-85551423,hs13:64217469-64217469;hs13:85592880-85592880,hs18:58836438-58836438;hs13:86096599-86096599,hs13:58470730-58470730;hs13:86665523-86665523,hs19:32816048-32816048;hs13:86679860-86679860,hs1:90487277-90487277;hs13:86686687-86686687,hs13:86697075-86697075;hs13:86696535-86696535,hs1:81081274-81081274;hs13:86964305-86964305,hs18:28094826-28094826;hs13:87105420-87105420,hs18:42975844-42975844;hs13:87467000-87467000,hs18:46898211-46898211;hs13:87995965-87995965,hs13:85424779-85424779;hs13:88131617-88131617,hs18:41974191-41974191;hs13:88496184-88496184,hs18:58933715-58933715;hs13:88588294-88588294,hs18:54074590-54074590;hs13:89942823-89942823,hs13:85300631-85300631;hs13:91297797-91297797,hs13:20480086-20480086;hs13:92205896-92205896,hs18:42470515-42470515;hs13:94072308-94072308,hs19:7501404-7501404;hs13:96929473-96929473,hs19:21639368-21639368;hs13:97061990-97061990,hs19:22894218-22894218;hs13:97972285-97972285,hs1:239139461-239139461;hs13:106899351-106899351,hs13:86361322-86361322;hs13:111962073-111962073,hs18:41973215-41973215;hs15:82219709-82219709,hs15:82216069-82216069;hs16:15114651-15114651,hs18:56530021-56530021;hs16:17868659-17868659,hs1:53683299-53683299;hs16:35086343-35086343,hs5:116180917-116180917;hs17:19804611-19804611,hs4:40932044-40932044;hs17:28606748-28606748,hs17:28607569-28607569;hs17:32280568-32280568,hs7:77912623-77912623;hs18:28190173-28190173,hs13:85908882-85908882;hs18:38821839-38821839,hs18:38821423-38821423;hs18:39057189-39057189,hs22:35638051-35638051;hs18:41922334-41922334,hs13:49707527-49707527;hs18:44144395-44144395,hs13:90509534-90509534;hs18:45104749-45104749,hs18:46868498-46868498;hs18:45405414-45405414,hs13:48500322-48500322;hs18:45787344-45787344,hs18:28175273-28175273;hs18:45997644-45997644,hs13:95568596-95568596;hs18:46031602-46031602,hs13:105348130-105348130;hs18:46402501-46402501,hs13:52710344-52710344;hs18:46719136-46719136,hs19:8773144-8773144;hs18:47939353-47939353,hs1:53648570-53648570;hs18:47971917-47971917,hs18:52905778-52905778;hs18:48604045-48604045,hs18:49365351-49365351;hs18:49038318-49038318,hs18:45394271-45394271;hs18:49048881-49048881,hs19:3054531-3054531;hs18:49306678-49306678,hs18:54935027-54935027;hs18:49966881-49966881,hs13:88550592-88550592;hs18:50132471-50132471,hs18:58797360-58797360;hs18:51095825-51095825,hs18:54834589-54834589;hs18:52467832-52467832,hs18:50918342-50918342;hs18:52806313-52806313,hs13:88408276-88408276;hs18:52925483-52925483,hs13:105755313-105755313;hs18:53703141-53703141,hs13:32484026-32484026;hs18:53873536-53873536,hs13:94070005-94070005;hs18:53891538-53891538,hs13:47481378-47481378;hs18:53996808-53996808,hs13:96025155-96025155;hs18:54029764-54029764,hs13:20120588-20120588;hs18:54703514-54703514,hs18:45068352-45068352;hs18:56510111-56510111,hs18:56509166-56509166;hs18:56550911-56550911,hs13:86193980-86193980;hs18:56583203-56583203,hs18:49141864-49141864;hs18:58476629-58476629,hs19:13320955-13320955;hs18:58615670-58615670,hs18:47853824-47853824;hs18:59019075-59019075,hs13:57661422-57661422;hs18:59066650-59066650,hs18:61316882-61316882;hs18:60003346-60003346,hs13:88963455-88963455;hs18:60870565-60870565,hs19:5741444-5741444;hs18:61516935-61516935,hs13:22417895-22417895;hs18:61566599-61566599,hs13:81759641-81759641;hs18:62266240-62266240,hs18:61268746-61268746;hs19:4026368-4026368,hs18:60664254-60664254;hs19:7500648-7500648,hs13:74896029-74896029;hs19:7970257-7970257,hs13:52547953-52547953;hs19:7971257-7971257,hs4:90436665-90436665;hs19:7972368-7972368,hs18:58913192-58913192;hs19:8773318-8773318,hs18:46719136-46719136;hs19:9114922-9114922,hs16:31480575-31480575;hs19:9160347-9160347,hs18:54911203-54911203;hs19:16178799-16178799,hs13:25132465-25132465;hs19:21586886-21586886,hs19:32899464-32899464;hs19:21783211-21783211,hs13:90445491-90445491;hs19:21797406-21797406,hs13:58566518-58566518;hs19:22665368-22665368,hs13:97053388-97053388;hs19:22805053-22805053,hs13:96882026-96882026;hs19:28852250-28852250,hs19:30961969-30961969;hs19:30104002-30104002,hs19:32308463-32308463;hs19:30251919-30251919,hs19:30160572-30160572;hs19:30375211-30375211,hs19:31803169-31803169;hs19:30654049-30654049,hs19:30654655-30654655;hs19:31007594-31007594,hs13:86520327-86520327;hs19:31254507-31254507,hs1:45525895-45525895;hs19:32049500-32049500,hs19:30300412-30300412;hs19:32274177-32274177,hs1:96075419-96075419;hs19:32276508-32276508,hs19:32052079-32052079;hs19:32415450-32415450,hs19:30848068-30848068;hs19:32553271-32553271,hs13:86665445-86665445;hs19:32624436-32624436,hs16:17869336-17869336;hs19:32662413-32662413,hs19:32662823-32662823;hs19:32729178-32729178,hs13:105725713-105725713;hs19:33086747-33086747,hs13:85570534-85570534;hs19:33655763-33655763,hs19:33655231-33655231;hs19:33687645-33687645,hs19:33688564-33688564;hs19:35838252-35838252,hs19:35839634-35839634;hs2:39608575-39608575,hs19:8540250-8540250;hs2:72866478-72866478,hs2:72865044-72865044;hs2:73439171-73439171,hs13:58619007-58619007;hs2:73787399-73787399,hs1:112573002-112573002;hs2:73792562-73792562,hs1:73810826-73810826;hs2:90451518-90451518,hs19:56121156-56121156;hs2:128936032-128936032,hs2:55829607-55829607;hs2:128936036-128936036,hs2:55829607-55829607;hs2:235334572-235334572,hs2:235258060-235258060;hs20:14765802-14765802,hs20:14776587-14776587;hs20:14775312-14775312,hs20:15096852-15096852;hs21:14346560-14346560,hs18:53425772-53425772;hs21:22092886-22092886,hs21:22076394-22076394;hs21:39798420-39798420,hs21:39871074-39871074;hs22:17876713-17876713,hs8:111846458-111846458;hs22:30101093-30101093,hs22:25479946-25479946;hs22:31955622-31955622,hs22:35811022-35811022;hs22:44409377-44409377,hs22:35804677-35804677;hs22:45322663-45322663,hs17:14652828-14652828;hs22:47901865-47901865,hs21:11051573-11051573;hs3:113453410-113453410,hs15:87430462-87430462;hs3:126677391-126677391,hs3:127208225-127208225;hs3:147604777-147604777,hs3:150087287-150087287;hs3:147604861-147604861,hs3:147585038-147585038;hs3:158751002-158751002,hs7:94061713-94061713;hs4:26093325-26093325,hs4:56783693-56783693;hs4:27013622-27013622,hs4:45839582-45839582;hs4:29077822-29077822,hs17:12366904-12366904;hs4:55210860-55210860,hs19:55782416-55782416;hs4:55659122-55659122,hs4:26062955-26062955;hs4:56346786-56346786,hs4:56347979-56347979;hs4:56360217-56360217,hs4:56360478-56360478;hs4:56787933-56787933,hs4:32912686-32912686;hs4:106368668-106368668,hs4:106374538-106374538;hs5:90025223-90025223,hs5:90032677-90032677;hs5:90041274-90041274,hs5:90032319-90032319;hs5:90165636-90165636,hs5:90032324-90032324;hs5:115398904-115398904,hs5:158376276-158376276;hs5:153258209-153258209,hs5:173890072-173890072;hs5:165812411-165812411,hs16:35053736-35053736;hs6:31700031-31700031,hs1:102149904-102149904;hs6:44818072-44818072,hs6:44821421-44821421;hs6:112663353-112663353,hs21:39474550-39474550;hs6:121699658-121699658,hs5:38715149-38715149;hs6:122422362-122422362,hs6:121699358-121699358;hs7:1472668-1472668,hsX:60520-60520;hs7:68983709-68983709,hs7:68983021-68983021;hs7:69020363-69020363,hs2:54035466-54035466;hs7:128049490-128049490,hs7:139856261-139856261;hs7:139856085-139856085,hs7:140000269-140000269;hs7:139856276-139856276,hs6:7307156-7307156;hs7:146236401-146236401,hs7:146238448-146238448;hs7:146607569-146607569,hs7:146236417-146236417;hs7:148427227-148427227,hs7:148428232-148428232;hs8:36397946-36397946,hs19:52826229-52826229;hs8:39263916-39263916,hs16:143796-143796;hs8:61176410-61176410,hs17:14400037-14400037;hs8:61873098-61873098,hs4:40621385-40621385;hs8:95332195-95332195,hs22:19955812-19955812;hs9:29151832-29151832,hs5:33117370-33117370;hs9:33342910-33342910,hs5:116160650-116160650;hsX:526791-526791,hsX:529215-529215;hsX:48745925-48745925,hs19:29777214-29777214 Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA Pediatric osteosarcoma is characterized by multiple somatic chromosomal lesions, including structural variations (SVs) and copy number alterations (CNAs). To define the landscape of somatic mutations in pediatric osteosarcoma, we performed whole-genome sequencing of DNA from 20 osteosarcoma tumor samples and matched normal tissue in a discovery cohort, as well as 14 samples in a validation cohort. Single-nucleotide variations (SNVs) exhibited a pattern of localized hypermutation called kataegis in 50% of the tumors. We identified p53 pathway lesions in all tumors in the discovery cohort, nine of which were translocations in the first intron of the TP53 gene. Beyond TP53, the RB1, ATRX, and DLG2 genes showed recurrent somatic alterations in 29%-53% of the tumors. These data highlight the power of whole-genome sequencing for identifying recurrent somatic alterations in cancer genomes that may be missed using other methods. GRCh37/hg19 Yes NA CTDB0384 Research 25186909 Inaki K, Menghi F, Woo XY, Wagner JP, Jacques PE, Lee YF, Shreckengast PT, Soon WW, Malhotra A, Teo AS, Hillmer AM, Khng AJ, Ruan X, Ong SH, Bertrand D, Nagarajan N, Karuturi RK, Miranda AH, Liu ET Systems consequences of amplicon formation in human breast cancer Genome Research 2014 Oct 22 Breast cancer Next Generation Sequencing Homo sapiens BT55 AB SOLiD 3 Plus System chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-26477557:0;chr17:26477558-53167545:-1;chr17:35327718-44040832:-1;chr17:35484752-32471649:1;chr17:35511432-35114153:1;chr17:44577064-47997384:-1;chr17:48218299-19265756:1;chr17:48761811-35187023:1;chr17:53167546-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-146364022:0;chr9:0-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs17:43485798-43485798,hs17:46036716-46036716;hs17:35336616-35336616,hs17:45874398-45874398;hs17:34388439-34388439,hs17:44664869-44664869;hs17:46780169-46780169,hs17:48815995-48815995;hs8:82011394-82011394,hs8:86729758-86729758;hs13:58728264-58728264,hs17:45198558-45198558 Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Genome, Singapore 138672, Singapore Chromosomal structural variations play an important role in determining the transcriptional landscape of human breast cancers. To assess the nature of these structural variations, we analyzed eight breast tumor samples with a focus on regions of gene amplification using mate-pair sequencing of long-insert genomic DNA with matched transcriptome profiling. We found that tandem duplications appear to be early events in tumor evolution, especially in the genesis of amplicons. In a detailed reconstruction of events on chromosome 17, we found large unpaired inversions and deletions connect a tandemly duplicated ERBB2 with neighboring 17q21.3 amplicons while simultaneously deleting the intervening BRCA1 tumor suppressor locus. This series of events appeared to be unusually common when examined in larger genomic data sets of breast cancers albeit using approaches with lesser resolution. Using siRNAs in breast cancer cell lines, we showed that the 17q21.3 amplicon harbored a significant number of weak oncogenes that appeared consistently coamplified in primary tumors. Down-regulation of BRCA1 expression augmented the cell proliferation in ERBB2-transfected human normal mammary epithelial cells. Coamplification of other functionally tested oncogenic elements in other breast tumors examined, such as RIPK2 and MYC on chromosome 8, also parallel these findings. Our analyses suggest that structural variations efficiently orchestrate the gain and loss of cancer gene cassettes that engage many oncogenic pathways simultaneously and that such oncogenic cassettes are favored during the evolution of a cancer. GRCh37/hg19 GSE57914 Yes MYH9,TTC28;CABIN1,BRD1;DESI1,EIF3L CTDB0385 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 4 Glioma Next Generation Sequencing Homo sapiens SJHGG003_A Illumina Genome Analyzer IIx or HiSeq chr10:0-319616:0;chr10:135524701-135534747:0;chr10:25879812-25885000:1;chr10:25885001-25885000:0;chr10:25885001-25889198:1;chr10:25889199-25889198:0;chr10:25889199-25894119:1;chr10:25894120-25894119:0;chr10:25894120-25897300:1;chr10:25897301-25897400:0;chr10:25897401-25897500:1;chr10:25897501-42753900:0;chr10:319617-320400:1;chr10:320401-320400:0;chr10:320401-408027:1;chr10:408028-408027:0;chr10:408028-710869:1;chr10:42753901-135524700:-1;chr10:710870-710869:0;chr10:710870-711300:1;chr10:711301-711300:0;chr10:711301-776100:1;chr10:776101-25879811:0;chr11:0-133700:0;chr11:13221610-13221609:0;chr11:13221610-13223467:-1;chr11:13223468-13223467:0;chr11:13223468-84279022:-1;chr11:133701-13221609:-1;chr11:134946401-135006516:0;chr11:84279023-84279022:0;chr11:84279023-84309912:-1;chr11:84309913-134946400:-1;chr11:84309913-84309912:0;chr12:0-57948297:0;chr12:122248387-124310873:1;chr12:124310874-133851895:0;chr12:57948298-57953600:1;chr12:57953601-57953600:0;chr12:57953601-57963600:1;chr12:57963601-57963600:0;chr12:57963601-58158690:1;chr12:58158691-58158690:0;chr12:58158691-58310360:1;chr12:58310361-58310360:0;chr12:58310361-58310600:1;chr12:58310601-58310600:0;chr12:58310601-58557840:1;chr12:58557841-58557840:0;chr12:58557841-58558200:1;chr12:58558201-58558200:0;chr12:58558201-58561515:1;chr12:58561516-58561515:0;chr12:58561516-58569000:1;chr12:58569001-58569000:0;chr12:58569001-58569700:1;chr12:58569701-58569700:0;chr12:58569701-58570000:1;chr12:58570001-58570000:0;chr12:58570001-58611116:1;chr12:58611117-58611116:0;chr12:58611117-58611438:1;chr12:58611439-58611438:0;chr12:58611439-58615200:1;chr12:58615201-58615200:0;chr12:58615201-58618300:1;chr12:58618301-58618300:0;chr12:58618301-58619700:1;chr12:58619701-58619700:0;chr12:58619701-58621800:1;chr12:58621801-122248386:0;chr13:0-115169878:0;chr14:0-19964300:0;chr14:107289501-107349540:0;chr14:19964301-22352300:-1;chr14:22352301-22352300:0;chr14:22352301-22974800:1;chr14:22974801-30217076:0;chr14:30217077-30350303:-1;chr14:30350304-107289500:-1;chr14:30350304-30350303:0;chr15:0-21885800:0;chr15:102521201-102531392:0;chr15:21885801-102521200:-1;chr16:0-74531130:0;chr16:74531131-74532821:-1;chr16:74532822-90354753:0;chr17:0-0:0;chr17:1-14258442:-1;chr17:14258443-57825593:0;chr17:57825594-58210400:1;chr17:58210401-58210400:0;chr17:58210401-58264300:1;chr17:58264301-58264400:0;chr17:58264401-58405372:1;chr17:58405373-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-161160900:0;chr1:161160901-161173000:-1;chr1:161173001-243265700:0;chr1:243265701-245044000:1;chr1:245044001-249250621:0;chr20:0-39609281:0;chr20:39609282-39788000:1;chr20:39788001-39788000:0;chr20:39788001-39804900:1;chr20:39804901-39804900:0;chr20:39804901-40217500:1;chr20:40217501-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-10500:0;chr4:10484201-10484200:0;chr4:10484201-10501699:1;chr4:10501-8158568:-1;chr4:10501700-10501699:0;chr4:10501700-19042264:-1;chr4:19042265-19042264:0;chr4:19042265-19043000:1;chr4:19043001-19043000:0;chr4:19043001-19049946:1;chr4:19049947-19049946:0;chr4:19049947-19054823:1;chr4:19054824-19054823:0;chr4:19054824-19055600:1;chr4:19055601-19055600:0;chr4:19055601-19088800:1;chr4:19088801-19088800:0;chr4:19088801-19089300:1;chr4:19089301-19089300:0;chr4:19089301-19093940:1;chr4:19093941-19093940:0;chr4:19093941-19094330:1;chr4:19094331-19094330:0;chr4:19094331-19094500:1;chr4:19094501-19094500:0;chr4:19094501-19102604:1;chr4:19102605-19102604:0;chr4:19102605-19115421:1;chr4:191043901-191154276:0;chr4:19115422-19115421:0;chr4:19115422-32457739:-1;chr4:32457740-32457739:0;chr4:32457740-32458805:1;chr4:32458806-32458805:0;chr4:32458806-33005500:-1;chr4:33005501-33005730:0;chr4:33005731-33012600:1;chr4:33012601-33012600:0;chr4:33012601-33013782:1;chr4:33013783-33013782:0;chr4:33013783-34569129:-1;chr4:34569130-34569129:0;chr4:34569130-34640647:1;chr4:34640648-34640647:0;chr4:34640648-34640657:1;chr4:34640658-34640657:0;chr4:34640658-34653188:1;chr4:34653189-34653188:0;chr4:34653189-34658100:1;chr4:34658101-34658100:0;chr4:34658101-34675530:1;chr4:34675531-34675530:0;chr4:34675531-35616000:1;chr4:35616001-35616000:0;chr4:35616001-36989108:-1;chr4:36989109-36989108:0;chr4:36989109-36992396:1;chr4:36992397-53595100:0;chr4:53595101-54513083:1;chr4:54513084-54513083:0;chr4:54513084-54513200:1;chr4:54513201-54513200:0;chr4:54513201-54562900:1;chr4:54562901-54562900:0;chr4:54562901-54565100:1;chr4:54565101-54565100:0;chr4:54565101-54565500:1;chr4:54565501-54565500:0;chr4:54565501-54568102:1;chr4:54568103-54568102:0;chr4:54568103-54575669:1;chr4:54575670-54575669:0;chr4:54575670-54576083:1;chr4:54576084-54576083:0;chr4:54576084-54576195:1;chr4:54576196-54576195:0;chr4:54576196-54577438:1;chr4:54577439-54577438:0;chr4:54577439-54862394:1;chr4:54862395-54862394:0;chr4:54862395-54863600:1;chr4:54863601-54863600:0;chr4:54863601-54864000:1;chr4:54864001-54864000:0;chr4:54864001-54868081:1;chr4:54868082-54868081:0;chr4:54868082-54872475:1;chr4:54872476-54872475:0;chr4:54872476-54876900:1;chr4:54876901-54876900:0;chr4:54876901-54879647:1;chr4:54879648-54879647:0;chr4:54879648-54881882:1;chr4:54881883-54881882:0;chr4:54881883-55040002:1;chr4:55040003-55040002:0;chr4:55040003-55139437:1;chr4:55139438-55139437:0;chr4:55139438-55140416:1;chr4:55140417-55140416:0;chr4:55140417-55212164:1;chr4:55212165-55212164:0;chr4:55212165-55358161:1;chr4:55358162-57015374:0;chr4:57015375-57025500:1;chr4:57025501-57259600:0;chr4:57259601-64706666:-1;chr4:64706667-64706666:0;chr4:64706667-64710500:1;chr4:64710501-64710500:0;chr4:64710501-64713100:1;chr4:64713101-64713500:0;chr4:64713501-64717100:1;chr4:64717101-64717100:0;chr4:64717101-64717400:1;chr4:64717401-64717400:0;chr4:64717401-64722629:1;chr4:64722630-64722629:0;chr4:64722630-69463216:-1;chr4:69463217-69463216:0;chr4:69463217-69491400:1;chr4:69491401-69491500:0;chr4:69491501-69493000:1;chr4:69493001-69493100:0;chr4:69493101-69495900:1;chr4:69495901-69495975:0;chr4:69495976-69503400:1;chr4:69503401-69503460:0;chr4:69503461-69505866:1;chr4:69505867-191043900:-1;chr4:69505867-69505866:0;chr4:8158569-8158568:0;chr4:8158569-8184900:1;chr4:8184901-8184900:0;chr4:8184901-8185264:1;chr4:8185265-10484200:-1;chr4:8185265-8185264:0;chr5:0-110271009:0;chr5:110271010-137498900:-1;chr5:137498901-138227100:0;chr5:138227101-145626781:-1;chr5:145626782-180915260:0;chr6:0-57623682:0;chr6:171050901-171115067:0;chr6:57623683-58075900:-1;chr6:58075901-61880300:0;chr6:61880301-171050900:-1;chr7:0-117407779:0;chr7:117407780-117408436:-1;chr7:117408437-135306487:0;chr7:135306488-135306625:-1;chr7:135306626-159138663:0;chr8:0-123740009:0;chr8:123740010-124433923:1;chr8:124433924-146364022:0;chr9:0-141213431:0;chrX:0-2699500:0;chrX:124406301-124406300:0;chrX:124406301-124414700:-1;chrX:124414701-124414700:0;chrX:124414701-144898200:1;chrX:144898201-144898200:0;chrX:144898201-144913900:1;chrX:144913901-144913900:0;chrX:144913901-154930300:1;chrX:154930301-155270560:0;chrX:2699501-124406300:1;chrY:0-2649500:0;chrY:26446401-59373566:0;chrY:2649501-26446400:-1 hs3:160202262-160202262,hs2:159281315-159281315;hs4:19115422-19115422,hs4:55358162-55358162;hs4:33005731-33005731,hs10:25879812-25879812;hs4:55140417-55140417,hs10:710870-710870;hs4:8185265-8185265,hs4:33013781-33013781;hs4:34569130-34569130,hs4:32457740-32457740;hs4:88005070-88005070,hs4:64706667-64706667;hs4:55140417-55140417,hs10:710870-710870;hs4:8158569-8158569,hs10:319617-319617;hs4:55139438-55139438,hs11:98307129-98307129;hs4:54872476-54872476,hs4:54513084-54513084;hs4:34675531-34675531,hs4:55212165-55212165;hs6:57623683-57623683,hs17:14258443-14258443;hs10:8040140-8040140,hs10:22018846-22018846;hs10:8040140-8040140,hs10:22018846-22018846;hs10:408028-408028,hs4:69491436-69491436;hs10:776144-776144,hs4:10501696-10501696;hs12:58614957-58614957,hs12:58614760-58614760;hs12:58158691-58158691,hs4:54868080-54868080;hs13:91558653-91558653,hs13:89295341-89295341 ABLIM2;ACOX3;AFAP1;AFF1;ARAP2;ARL9;BOD1L;C1orf101;C4orf14;C8orf76;CCKAR;CENPC1;CHIC2;CLNK;CXorf51;DCAF16;DEFB131;DRD5;DTHD1;DUX2;DUX4;DUX4L2;DUX4L3;DUX4L4;DUX4L5;DUX4L6;DUX4L7;EPHA5;FAM184B;FIP1L1;GBA3;GPCRLTM7;GPR125;GPR78;GRPEL1;GSX2;HOPX;HS3ST1;HTRA3;IGFBP7;LCORL;LNX1;LOC100288413;LOC144776;LOC653486;LPHN3;MED28;METTL19;NCAPG;NKX3-2;PACRGL;PAICS;PCDH7;PDGFRA;POLR2B;PPAT;PSAPL1;RAB28;RASL11B;RBPJ;REST;SCFD2;SH3TC1;SLC2A9;SORCS2;SRP72;STAP1;STIM2;TBC1D19;TECRL;TMPRSS11B;UBA6;UGT2A3;UGT2B10;UGT2B11;UGT2B15;UGT2B17;UGT2B7;WDR1;YTHDC1;ZNF518B;ZNF595;ZNF718; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes DIP2C,PDGFRA CTDB0386 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 15 Glioma Next Generation Sequencing Homo sapiens SJHGG004_D Illumina Genome Analyzer IIx or HiSeq chr10:0-42355000:0;chr10:135476901-135534747:0;chr10:42355001-52665706:-1;chr10:52665707-52665706:0;chr10:52665707-69909310:-1;chr10:69909311-69909310:0;chr10:69909311-85091787:-1;chr10:85091788-85091787:0;chr10:85091788-85095874:-1;chr10:85095875-85095874:0;chr10:85095875-85101400:-1;chr10:85101401-85101645:0;chr10:85101646-85107120:-1;chr10:85107121-85107120:0;chr10:85107121-85121200:-1;chr10:85121201-85121745:0;chr10:85121746-85158900:-1;chr10:85158901-85158900:0;chr10:85158901-89580853:-1;chr10:89580854-89580853:0;chr10:89580854-89693652:-1;chr10:89693653-135476900:-1;chr10:89693653-89693652:0;chr11:0-168400:0;chr11:134946401-135006516:0;chr11:168401-2466500:-1;chr11:2466501-134946400:-1;chr11:2466501-2466500:0;chr12:0-133851895:0;chr13:0-19020700:0;chr13:115109801-115169878:0;chr13:19020701-115109800:-1;chr14:0-19191600:0;chr14:107289501-107349540:0;chr14:19191601-22033026:1;chr14:22033027-22033026:0;chr14:22033027-22034100:-1;chr14:22034101-22034200:0;chr14:22034201-22073565:1;chr14:22073566-107289500:-1;chr14:22073566-22073565:0;chr15:0-20000000:0;chr15:20000001-82664400:-1;chr15:82664401-83229106:0;chr15:83229107-83234500:1;chr15:83234501-83234500:0;chr15:83234501-83305857:1;chr15:83305858-83305857:0;chr15:83305858-83609926:1;chr15:83609927-83609926:0;chr15:83609927-83709380:1;chr15:83709381-83709380:0;chr15:83709381-83833182:1;chr15:83833183-83833182:0;chr15:83833183-83886500:1;chr15:83886501-83886500:0;chr15:83886501-84958300:1;chr15:84958301-85080346:0;chr15:85080347-86293000:1;chr15:86293001-86293000:0;chr15:86293001-86313100:1;chr15:86313101-86313100:0;chr15:86313101-86656300:1;chr15:86656301-86656300:0;chr15:86656301-86674945:1;chr15:86674946-86674945:0;chr15:86674946-87172300:1;chr15:87172301-87172300:0;chr15:87172301-87177448:1;chr15:87177449-87177448:0;chr15:87177449-87531100:1;chr15:87531101-87531100:0;chr15:87531101-87659900:1;chr15:87659901-87659900:0;chr15:87659901-88288100:1;chr15:88288101-88288100:0;chr15:88288101-88660093:1;chr15:88660094-88660093:0;chr15:88660094-89676083:1;chr15:89676084-89676083:0;chr15:89676084-89804637:1;chr15:89804638-89804637:0;chr15:89804638-90278566:1;chr15:90278567-96729370:0;chr15:96729371-96770681:1;chr15:96770682-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-25583775:0;chr18:25583776-25705352:-1;chr18:25705353-78077248:0;chr19:0-158500:0;chr19:11485901-19965815:1;chr19:158501-7996700:-1;chr19:19965816-19965815:0;chr19:19965816-24453400:-1;chr19:24453401-27731800:0;chr19:27731801-59118800:-1;chr19:59118801-59128983:0;chr19:7996701-11485900:0;chr1:0-249250621:0;chr20:0-60000:0;chr20:18439844-18439843:0;chr20:18439844-18983600:1;chr20:18983601-19284572:0;chr20:19284573-22770329:-1;chr20:22770330-63025520:0;chr20:60001-18439843:-1;chr21:0-14338400:0;chr21:14338401-48119800:-1;chr21:48119801-48129895:0;chr22:0-17039000:0;chr22:17039001-17652692:-1;chr22:17652693-17657900:0;chr22:17657901-17804279:-1;chr22:17804280-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-90700:0;chr6:53410001-98489375:0;chr6:90701-53410000:-1;chr6:98489376-98642109:-1;chr6:98642110-171115067:0;chr7:0-159138663:0;chr8:0-74565145:0;chr8:74565146-74754778:1;chr8:74754779-146364022:0;chr9:0-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs15:85864830-85864830,hs15:86160094-86160094;hs14:22033027-22033027,hs14:22073566-22073566;hs20:18439844-18439844,hs14:22034083-22034083;hs19:33121294-33121294,hs10:3446375-3446375;hs15:85865305-85865305,hs15:89250459-89250459;hs19:19965816-19965816,hsX:1781376-1781376;hs15:95610288-95610288,hs15:99346209-99346209;hs3:169746022-169746022,hs15:95592769-95592769;hs10:85091788-85091788,hs10:85120150-85120150;hs15:86674946-86674946,hs15:87177449-87177449;hs15:89408289-89408289,hs15:88945062-88945062;hs15:86185075-86185075,hs15:84313872-84313872;hs15:89804638-89804638,hs15:88977330-88977330;hs15:85357531-85357531,hs15:89292296-89292296;hs15:85167984-85167984,hs15:83709381-83709381 ABHD2;ACAN;ADAMTSL3;AEN;AGBL1;AKAP13;ALPK3;AP3B2;BNC1;BTBD1;C10orf99;C15orf40;C15orf42;C19orf12;CPEB1;DET1;EFTUD1;FAM103A1;FAM154B;FANCI;FSD2;GOLGA6L10;GOLGA6L6;HAPLN3;HDGFRP3;HOMER2;IGF1R;ISG20;KIF7;KLHL25;LOC100128496;LOC645781;LOC653486;MEX3B;MFGE8;MRPL46;MRPS11;NMB;NTRK3;OR4M2;OR4N4;PDE8A;PEX11A;PLIN1;POLG;POTEB;RHCG;RLBP1;SEC11A;SH3GL3;SLC28A1;TM6SF1;TMC3;WDR73;WDR93;WHAMM;ZNF592;ZSCAN2; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes ABHD2,AKAP13;BTBD1,CPEB1;BTBD1,NTRK3;CPEB1,NTRK3;UBE2Q2P1,HDGFRP3 CTDB0387 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May X Glioma Next Generation Sequencing Homo sapiens SJHGG007_A Illumina Genome Analyzer IIx or HiSeq chr10:0-135534747:0;chr11:0-55362900:0;chr11:106865708-106866660:-1;chr11:106866661-106880100:0;chr11:106880101-116354984:-1;chr11:116354985-135006516:0;chr11:55362901-63762408:-1;chr11:63762409-68314700:0;chr11:68314701-70395737:-1;chr11:70395738-106865707:0;chr12:0-34485100:0;chr12:34485101-34505100:-1;chr12:34505101-64597831:0;chr12:64597832-64597915:1;chr12:64597916-133851895:0;chr13:0-19338000:0;chr13:19338001-70111100:-1;chr13:70111101-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-20271200:0;chr17:20271201-22262900:1;chr17:22262901-29683303:0;chr17:29683304-29684973:1;chr17:29684974-81195210:0;chr18:0-78077248:0;chr19:0-158500:0;chr19:158501-397400:1;chr19:397401-551800:0;chr19:551801-572300:1;chr19:572301-59128983:0;chr1:0-144454200:0;chr1:144454201-249240500:1;chr1:249240501-249250621:0;chr20:0-60000:0;chr20:26317701-63025520:0;chr20:60001-26317700:-1;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-133825295:0;chr6:133825296-135577686:-1;chr6:135577687-171115067:0;chr7:0-124170500:0;chr7:124170501-124278903:1;chr7:124278904-124305859:0;chr7:124305860-141747700:1;chr7:141747701-141747840:0;chr7:141747841-141775645:1;chr7:141775646-141775645:0;chr7:141775646-146953908:1;chr7:146953909-146953908:0;chr7:146953909-147164300:1;chr7:147164301-147164300:0;chr7:147164301-147294114:1;chr7:147294115-147294171:0;chr7:147294172-147329892:1;chr7:147329893-147329892:0;chr7:147329893-147344346:1;chr7:147344347-147344346:0;chr7:147344347-159128500:-1;chr7:159128501-159138663:0;chr8:0-146364022:0;chr9:0-10000:0;chr9:10001-39638800:-1;chr9:39638801-89558853:0;chr9:89558854-89560838:-1;chr9:89560839-141213431:0;chrX:0-127371980:0;chrX:127371981-127381000:1;chrX:127381001-127929013:0;chrX:127929014-127929393:1;chrX:127929394-128870386:0;chrX:128870387-128870533:1;chrX:128870534-128870533:0;chrX:128870534-128870818:1;chrX:128870819-128870818:0;chrX:128870819-128870853:1;chrX:128870854-128870853:0;chrX:128870854-128870958:1;chrX:128870959-128870958:0;chrX:128870959-128871109:1;chrX:128871110-128871109:0;chrX:128871110-128871248:1;chrX:128871249-128871248:0;chrX:128871249-128871276:1;chrX:128871277-128871276:0;chrX:128871277-128871421:1;chrX:128871422-128871421:0;chrX:128871422-128871484:1;chrX:128871485-128871484:0;chrX:128871485-128871563:1;chrX:128871564-128871563:0;chrX:128871564-128871902:1;chrX:128871903-128871902:0;chrX:128871903-128871966:1;chrX:128871967-128942253:0;chrX:128942254-129069878:1;chrX:129069879-131390128:0;chrX:131390129-131412063:1;chrX:131412064-131413081:0;chrX:131413082-131438243:1;chrX:131438244-131438243:0;chrX:131438244-131438265:1;chrX:131438266-131438265:0;chrX:131438266-131438518:1;chrX:131438519-131438518:0;chrX:131438519-131438569:1;chrX:131438570-131438569:0;chrX:131438570-131438697:1;chrX:131438698-131438697:0;chrX:131438698-131438816:1;chrX:131438817-131438816:0;chrX:131438817-131439360:1;chrX:131439361-131441477:0;chrX:131441478-131443085:1;chrX:131443086-131443085:0;chrX:131443086-131444117:1;chrX:131444118-131447200:0;chrX:131447201-131447284:1;chrX:131447285-131447284:0;chrX:131447285-131447478:1;chrX:131447479-131447478:0;chrX:131447479-131447600:1;chrX:131447601-131447600:0;chrX:131447601-131448419:1;chrX:131448420-131454500:0;chrX:131454501-131456182:1;chrX:131456183-134229769:0;chrX:134229770-134230082:1;chrX:134230083-134235682:0;chrX:134235683-134235780:1;chrX:134235781-134235780:0;chrX:134235781-134236334:1;chrX:134236335-134236334:0;chrX:134236335-134236561:1;chrX:134236562-134246828:0;chrX:134246829-134246894:1;chrX:134246895-134246894:0;chrX:134246895-134247016:1;chrX:134247017-134247016:0;chrX:134247017-134247216:1;chrX:134247217-135480500:0;chrX:135480501-135503157:1;chrX:135503158-142667655:0;chrX:142667656-142689555:1;chrX:142689556-142689555:0;chrX:142689556-142689760:1;chrX:142689761-142689760:0;chrX:142689761-142689892:1;chrX:142689893-142689892:0;chrX:142689893-142690042:1;chrX:142690043-143256900:0;chrX:143256901-143310858:1;chrX:143310859-143310858:0;chrX:143310859-143311096:1;chrX:143311097-143311096:0;chrX:143311097-144354565:1;chrX:144354566-144355187:0;chrX:144355188-152989100:1;chrX:152989101-152989100:0;chrX:152989101-153076600:1;chrX:153076601-153076600:0;chrX:153076601-154930300:1;chrX:154930301-155270560:0;chrY:0-2649500:0;chrY:2649501-28817600:-1;chrY:28817601-59373566:0 hs17:29684974-29684974,hs11:99252689-99252689;hs11:99252874-99252874,hs17:29683304-29683304;hsX:128870472-128870472,hsX:131438519-131438519;hsX:131448163-131448163,hsX:131438484-131438484;hsX:131447601-131447601,hsX:131438266-131438266;hsX:131438437-131438437,hsX:128870472-128870472;hsX:128871527-128871527,hsX:131438750-131438750;hsX:128871110-128871110,hsX:128870670-128870670;hsX:129069879-129069879,hsX:131412064-131412064;hsX:127921466-127921466,hsX:128870979-128870979;hsX:134247205-134247205,hsX:128870976-128870976;hsX:143311097-143311097,hsX:142667656-142667656;hsX:128870625-128870625,hsX:131438842-131438842;hsX:134233095-134233095,hsX:131447151-131447151;hsX:128871359-128871359,hsX:128870800-128870800;hsX:131438655-131438655,hsX:142689893-142689893;hsX:128871563-128871563,hsX:134230174-134230174;hsX:131443086-131443086,hsX:142690043-142690043;hs11:70395738-70395738,hs11:63762409-63762409;hsX:127921323-127921323,hsX:128871432-128871432;hsX:131438266-131438266,hsX:131390129-131390129 ABCD1;ARHGAP4;AVPR2;BCAP31;C12orf66;C17orf51;C9orf66;CLIC2;CXorf1;CXorf51;DUSP9;FAM58A;FMR1;FMR1NB;GPR112;H2AFB2;IDH3G;L1CAM;LOC154872;LOC646627;NAA10;PDZD4;PLXNB3;PNCK;RAB39B;SLC6A8;SLITRK2;SPANXN1;SRPK3;SSR4;TMLHE;UTP14A;VBP1;ZDHHC9; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes NA CTDB0388 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 7 Glioma Next Generation Sequencing Homo sapiens SJHGG009_A Illumina Genome Analyzer IIx or HiSeq chr10:0-71700:0;chr10:135476901-135534747:0;chr10:39154801-42397500:0;chr10:42397501-135476900:1;chr10:71701-39154800:1;chr11:0-133700:0;chr11:133701-33358870:1;chr11:134923601-134946400:-1;chr11:134946401-135006516:0;chr11:33358871-33358870:0;chr11:33358871-33499500:1;chr11:33499501-33499500:0;chr11:33499501-36302000:1;chr11:36302001-36302000:0;chr11:36302001-36402368:1;chr11:36402369-36402368:0;chr11:36402369-42060600:1;chr11:42060601-42060600:0;chr11:42060601-42229819:1;chr11:42229820-42268811:0;chr11:42268812-43804586:1;chr11:43804587-43804586:0;chr11:43804587-44203059:1;chr11:44203060-44203059:0;chr11:44203060-49718400:1;chr11:49718401-68164538:0;chr11:68164539-68656400:1;chr11:68656401-68656400:0;chr11:68656401-71229300:1;chr11:71229301-134923600:0;chr12:0-60700:0;chr12:133841501-133851895:0;chr12:38173487-38173486:0;chr12:38173487-38173907:1;chr12:38173908-38173907:0;chr12:38173908-38312286:1;chr12:38312287-38312286:0;chr12:38312287-38314476:1;chr12:38314477-38314476:0;chr12:38314477-38316609:1;chr12:38316610-38316609:0;chr12:38316610-38507400:1;chr12:38507401-38507400:0;chr12:38507401-38792988:1;chr12:38792989-38792988:0;chr12:38792989-38853764:1;chr12:38853765-38853764:0;chr12:38853765-38854563:1;chr12:38854564-38854563:0;chr12:38854564-38856100:1;chr12:38856101-38856200:0;chr12:38856201-39610824:1;chr12:39610825-39610824:0;chr12:39610825-39620400:1;chr12:39620401-39620400:0;chr12:39620401-39627046:1;chr12:39627047-39627046:0;chr12:39627047-39629862:1;chr12:39629863-39629862:0;chr12:39629863-39639529:1;chr12:39639530-39639529:0;chr12:39639530-39712373:1;chr12:39712374-39712373:0;chr12:39712374-39717962:1;chr12:39717963-39717962:0;chr12:39717963-39745127:1;chr12:39745128-39745127:0;chr12:39745128-39745406:1;chr12:39745407-39745406:0;chr12:39745407-39803052:1;chr12:39803053-39803052:0;chr12:39803053-39803797:1;chr12:39803798-39803797:0;chr12:39803798-39847187:1;chr12:39847188-39847187:0;chr12:39847188-39999826:1;chr12:39999827-39999826:0;chr12:39999827-40212630:1;chr12:40212631-40212630:0;chr12:40212631-40688681:1;chr12:40688682-40688681:0;chr12:40688682-40713320:1;chr12:40713321-40713320:0;chr12:40713321-40770415:1;chr12:40770416-40770415:0;chr12:40770416-40929589:1;chr12:40929590-40929589:0;chr12:40929590-41056798:1;chr12:41056799-41056798:0;chr12:41056799-41155666:1;chr12:41155667-41155666:0;chr12:41155667-41160013:1;chr12:41160014-41160013:0;chr12:41160014-41263446:1;chr12:41263447-41263446:0;chr12:41263447-41569417:1;chr12:41569418-41569417:0;chr12:41569418-41598772:1;chr12:41598773-41598772:0;chr12:41598773-41607583:1;chr12:41607584-133841500:1;chr12:41607584-41607583:0;chr12:60701-38173486:1;chr13:0-19020700:0;chr13:115109801-115169878:0;chr13:19020701-115109800:1;chr14:0-107349540:0;chr15:0-20000000:0;chr15:102465301-102531392:0;chr15:20000001-35297736:1;chr15:35297737-35297736:0;chr15:35297737-35309792:1;chr15:35309793-35309792:0;chr15:35309793-35315716:1;chr15:35315717-35315716:0;chr15:35315717-69109900:1;chr15:69109901-102465300:1;chr15:69109901-69109900:0;chr16:0-60000:0;chr16:60001-90292700:1;chr16:90292701-90354753:0;chr17:0-15472400:0;chr17:15472401-16531563:1;chr17:16531564-16531563:0;chr17:16531564-17419160:1;chr17:17419161-17419160:0;chr17:17419161-19701431:1;chr17:19701432-19701431:0;chr17:19701432-19750042:1;chr17:19750043-19750042:0;chr17:19750043-21563400:1;chr17:21563401-21670200:0;chr17:21670201-81195100:1;chr17:81195101-81195210:0;chr18:0-78077248:0;chr19:0-158500:0;chr19:158501-59118800:1;chr19:59118801-59128983:0;chr1:0-10100:0;chr1:10101-54171200:1;chr1:102242625-102242666:0;chr1:102242667-149035800:1;chr1:149035801-149035800:0;chr1:149035801-149204100:-1;chr1:149204101-149646000:0;chr1:149646001-249240500:1;chr1:249240501-249250621:0;chr1:54171201-54171200:0;chr1:54171201-54241609:1;chr1:54241610-54241609:0;chr1:54241610-56062273:1;chr1:56062274-56062273:0;chr1:56062274-56194700:1;chr1:56194701-56194800:0;chr1:56194801-57287043:1;chr1:57287044-102242624:1;chr1:57287044-57287043:0;chr20:0-60000:0;chr20:19669501-19669500:0;chr20:19669501-19685417:1;chr20:19685418-19685417:0;chr20:19685418-19784054:1;chr20:19784055-19924774:0;chr20:19924775-19946227:1;chr20:19946228-19946227:0;chr20:19946228-19946309:1;chr20:19946310-19946309:0;chr20:19946310-19946798:1;chr20:19946799-19946798:0;chr20:19946799-19967000:1;chr20:19967001-19967000:0;chr20:19967001-62918900:1;chr20:60001-19669500:1;chr20:62918901-63025520:0;chr21:0-14338400:0;chr21:14338401-33496500:1;chr21:33496501-33496500:0;chr21:33496501-33520100:1;chr21:33520101-33520200:0;chr21:33520201-34785736:1;chr21:34785737-34785736:0;chr21:34785737-34786036:1;chr21:34786037-34786036:0;chr21:34786037-48119800:1;chr21:48119801-48129895:0;chr22:0-16847900:0;chr22:16847901-49254240:1;chr22:49254241-49254240:0;chr22:49254241-49335475:1;chr22:49335476-49335475:0;chr22:49335476-51234500:1;chr22:51234501-51304566:0;chr2:0-10000:0;chr2:10001-115940300:1;chr2:115940301-116003600:0;chr2:116003601-243094700:1;chr2:243094701-243199373:0;chr3:0-60200:0;chr3:197948401-198022430:0;chr3:60201-197948400:1;chr4:0-77300:0;chr4:133958701-134334400:0;chr4:134334401-134632800:1;chr4:134632801-134751200:0;chr4:134751201-191043900:1;chr4:191043901-191154276:0;chr4:77301-133958700:1;chr5:0-11700:0;chr5:11701-40488806:1;chr5:180785401-180915260:0;chr5:40488807-40488806:0;chr5:40488807-40489369:1;chr5:40489370-180785400:1;chr5:40489370-40489369:0;chr6:0-90700:0;chr6:160362701-171050900:1;chr6:171050901-171115067:0;chr6:66662245-69586178:0;chr6:69586179-69667700:1;chr6:69667701-160362700:0;chr6:90701-66662244:1;chr7:0-10000:0;chr7:10001-1188715:1;chr7:100080126-100080125:0;chr7:100080126-100248746:1;chr7:100248747-100248746:0;chr7:100248747-107910634:1;chr7:107910635-107910634:0;chr7:107910635-107913300:1;chr7:107913301-107913500:0;chr7:107913501-108017400:1;chr7:108017401-108017400:0;chr7:108017401-108131271:1;chr7:108131272-108131271:0;chr7:108131272-112845700:1;chr7:112845701-112845700:0;chr7:112845701-113050031:1;chr7:113050032-113050031:0;chr7:113050032-113050856:1;chr7:113050857-113050856:0;chr7:113050857-113365728:1;chr7:113365729-113365728:0;chr7:113365729-113581123:1;chr7:113581124-113581123:0;chr7:113581124-113581437:1;chr7:113581438-113581437:0;chr7:113581438-113991100:1;chr7:113991101-113991100:0;chr7:113991101-116294004:1;chr7:116294005-116294004:0;chr7:116294005-116500095:1;chr7:116500096-116500095:0;chr7:116500096-116815625:1;chr7:116815626-116815625:0;chr7:116815626-117013200:1;chr7:117013201-117013200:0;chr7:117013201-117406018:1;chr7:117406019-117406018:0;chr7:117406019-157989630:1;chr7:1188716-1188715:0;chr7:1188716-6078500:1;chr7:157989631-157989630:0;chr7:157989631-157991198:1;chr7:157991199-157991198:0;chr7:157991199-159128500:1;chr7:159128501-159138663:0;chr7:28995201-28995200:0;chr7:28995201-38364400:1;chr7:38364401-38364400:0;chr7:38364401-61917100:1;chr7:6078501-28995200:1;chr7:6078501-6078500:0;chr7:61917101-61968100:0;chr7:61968101-66173900:1;chr7:66173901-66173900:0;chr7:66173901-83658014:1;chr7:83658015-83658014:0;chr7:83658015-84152121:1;chr7:84152122-84152121:0;chr7:84152122-84152200:1;chr7:84152201-84152400:0;chr7:84152401-86644072:1;chr7:86644073-86644072:0;chr7:86644073-86645053:1;chr7:86645054-86645053:0;chr7:86645054-86646084:1;chr7:86646085-86646084:0;chr7:86646085-86646668:1;chr7:86646669-86646668:0;chr7:86646669-86703320:1;chr7:86703321-86703320:0;chr7:86703321-86820975:1;chr7:86820976-86820975:0;chr7:86820976-88413799:1;chr7:88413800-88413799:0;chr7:88413800-88414682:1;chr7:88414683-88414682:0;chr7:88414683-88473230:1;chr7:88473231-88473230:0;chr7:88473231-88555100:1;chr7:88555101-88560801:0;chr7:88560802-88617056:1;chr7:88617057-88617056:0;chr7:88617057-88617544:1;chr7:88617545-88617544:0;chr7:88617545-88622689:1;chr7:88622690-88622689:0;chr7:88622690-88622889:1;chr7:88622890-88622889:0;chr7:88622890-88623642:1;chr7:88623643-88623642:0;chr7:88623643-88623989:1;chr7:88623990-88624100:0;chr7:88624101-88637622:1;chr7:88637623-88637622:0;chr7:88637623-88640446:1;chr7:88640447-88640446:0;chr7:88640447-88653167:1;chr7:88653168-88653167:0;chr7:88653168-90908273:1;chr7:90908274-90908273:0;chr7:90908274-90915961:1;chr7:90915962-90915961:0;chr7:90915962-90920685:1;chr7:90920686-90920685:0;chr7:90920686-90946721:1;chr7:90946722-90950540:0;chr7:90950541-90972508:1;chr7:90972509-90972508:0;chr7:90972509-90974864:1;chr7:90974865-90974864:0;chr7:90974865-91067761:1;chr7:91067762-91067761:0;chr7:91067762-92242201:1;chr7:92242202-92242201:0;chr7:92242202-92873778:1;chr7:92873779-92873778:0;chr7:92873779-92874370:1;chr7:92874371-92874370:0;chr7:92874371-92904863:1;chr7:92904864-93536940:0;chr7:93536941-96773435:1;chr7:96773436-96773435:0;chr7:96773436-99905300:1;chr7:99905301-99914200:0;chr7:99914201-100080125:1;chr8:0-33500:0;chr8:127194901-127194900:0;chr8:127194901-130596434:1;chr8:130596435-130596434:0;chr8:130596435-130675017:1;chr8:130675018-130675017:0;chr8:130675018-146303800:1;chr8:146303801-146364022:0;chr8:33501-47636854:1;chr8:47636855-47636854:0;chr8:47636855-70647335:1;chr8:70647336-70648844:0;chr8:70648845-71218348:1;chr8:71218349-71218348:0;chr8:71218349-75751493:1;chr8:75751494-127194900:1;chr8:75751494-75751493:0;chr9:0-10000:0;chr9:10001-141102500:1;chr9:141102501-141213431:0;chrX:0-21998600:0;chrX:21998601-22080300:-1;chrX:22080301-31174800:0;chrX:31174801-31421100:-1;chrX:31421101-53400800:0;chrX:53400801-56696300:1;chrX:56696301-69594300:0;chrX:69594301-74602600:1;chrX:74602601-155270560:0;chrY:0-20331600:0;chrY:20331601-28817600:-1;chrY:28817601-59373566:0 hs12:39712374-39712374,hs12:39803053-39803053;hs7:116294005-116294005,hs12:40713318-40713318;hs7:116815626-116815626,hs21:34785737-34785737;hs12:39321721-39321721,hs11:7261385-7261385;hs11:7316099-7316099,hs1:112115501-112115501;hs7:88413827-88413827,hs7:88617545-88617545;hs7:10073848-10073848,hs7:10116600-10116600;hs7:113050857-113050857,hs12:39847188-39847188;hs12:39745407-39745407,hs7:90969631-90969631;hs20:19946228-19946228,hs20:19924775-19924775;hs7:117406019-117406019,hs7:157991199-157991199;hs12:38166571-38166571,hs7:108112775-108112775;hs11:18782557-18782557,hs11:14061845-14061845;hs7:88468475-88468475,hs12:39745128-39745128;hs12:38314477-38314477,hs7:108131272-108131272;hs5:40488800-40488800,hs5:40903036-40903036;hs12:41263008-41263008,hs7:113581438-113581438;hs6:69586179-69586179,hs11:42268812-42268812;hs20:19946228-19946228,hs20:19924775-19924775;hs7:93536941-93536941,hs7:92874371-92874371;hs1:57287044-57287044,hs7:86646669-86646669;hs17:19701432-19701432,hs17:19750043-19750043;hs12:39601641-39601641,hs7:88636338-88636338;hs12:40212631-40212631,hs7:113050032-113050032;hs7:113365729-113365729,hs12:40929590-40929590;hs12:39607882-39607882,hs7:88413777-88413777;hs7:116815626-116815626,hs21:34785737-34785737;hs20:19946799-19946799,hs20:19946223-19946223;hs21:34786037-34786037,hs7:100248747-100248747;hs7:90915962-90915962,hs7:90969953-90969953;hs7:108129790-108129790,hs12:38312287-38312287;hs15:68083464-68083464,hs15:99162473-99162473;hs7:86703321-86703321,hs7:86644073-86644073;hs7:91067762-91067762,hs12:39627047-39627047;hs1:56194701-56194701,hs7:92242202-92242202;hs7:116465984-116465984,hs12:40652829-40652829;hs11:36402369-36402369,hs11:68689001-68689001;hs10:45293715-45293715,hs1:76310109-76310109;hs21:34786037-34786037,hs7:100248747-100248747;hs7:84152311-84152311,hs12:39803798-39803798;hs20:19946228-19946228,hs20:19924775-19924775;hs7:88468475-88468475,hs12:39745128-39745128;hs12:38507372-38507372,hs12:38173431-38173431;hs7:88414617-88414617,hs7:88625420-88625420;hs9:82697356-82697356,hs9:94005095-94005095;hs18:40045135-40045135,hs5:31998216-31998216;hs7:88414440-88414440,hs7:88623990-88623990;hs7:93536941-93536941,hs7:92874371-92874371;hs7:117406019-117406019,hs7:157991199-157991199;hs20:19946799-19946799,hs20:19946223-19946223;hs7:88622690-88622690,hs12:39639530-39639530;hs7:157989631-157989631,hs12:41598773-41598773;hs7:84152122-84152122,hs12:39610825-39610825;hs7:157989631-157989631,hs12:41598773-41598773;hs7:88468475-88468475,hs12:39745128-39745128;hs12:40770416-40770416,hs12:41155667-41155667;hs5:31225486-31225486,hs5:32654333-32654333;hs7:108131315-108131315,hs12:41261949-41261949;hs4:67403436-67403436,hs5:1957113-1957113;hs1:68995754-68995754,hs10:48424974-48424974;hs7:90920686-90920686,hs12:39717963-39717963;hs1:111319853-111319853,hs7:99598937-99598937;hs12:39712374-39712374,hs12:39803053-39803053;hs22:44963845-44963845,hs10:129335123-129335123;hs20:19946799-19946799,hs20:19946223-19946223;hs7:113581568-113581568,hs12:40928739-40928739;hs11:36402369-36402369,hs11:68689001-68689001;hs12:41569418-41569418,hs12:41607584-41607584;hs7:108131315-108131315,hs12:41261949-41261949;hs7:92873779-92873779,hs7:92904864-92904864;hs11:77494008-77494008,hs5:151134882-151134882;hs7:92873779-92873779,hs7:92904864-92904864;hs7:117406019-117406019,hs7:157991199-157991199;hs7:91912720-91912720,hs7:66494424-66494424;hs7:157989631-157989631,hs12:41598773-41598773;hs18:11776823-11776823,hs10:95623582-95623582;hs8:75751494-75751494,hs8:75754424-75754424;hs7:90972509-90972509,hs7:88560802-88560802;hs12:40688682-40688682,hs7:117013151-117013151;hs1:54241610-54241610,hs7:96773436-96773436;hs7:91912720-91912720,hs7:66494424-66494424;hs12:39626877-39626877,hs7:88623643-88623643;hs20:19946799-19946799,hs20:19946223-19946223;hs15:68453333-68453333,hs15:35297737-35297737;hs10:46004233-46004233,hs7:86972930-86972930;hs7:93536941-93536941,hs7:92874371-92874371;hs12:40688682-40688682,hs7:117013151-117013151 ABCB1;ABCB4;ACN9;ACTL6B;ADAM22;AGFG2;AIMP2;AKAP9;AMPH;ANKIB1;ANKRD7;ASL;ASNS;ASZ1;BET1;C11orf74;C11orf96;C12orf40;C15orf41;C17orf51;C1orf123;C1orf168;C4orf33;C7orf23;C7orf36;C7orf42;C7orf47;C7orf50;C7orf51;C7orf53;C7orf60;C7orf61;C7orf62;C7orf63;C7orf64;C7orf66;C7orf70;C8orf33;C8orf34;C9orf66;CACNA2D1;CAPZA2;CASD1;CAV1;CAV2;CCDC132;CDK14;CDK6;CFTR;CHCHD2;CHN2;CLDN12;COL1A2;COX19;CPVL;CRCP;CREB5;CROT;CTTNBP2;CYP2W1;CYP51A1;CYTH3;DBF4;DLD;DLX5;DLX6;DMTF1;DNAJB6;DNAJB9;EIF2AK1;EPDR1;EPO;ESYT2;FAM133B;FBXO24;FLJ42280;FOXP2;FZD1;GAL3ST4;GATAD1;GATS;GIGYF1;GNB2;GNG11;GNGT1;GPC2;GPCRLTM7;GPER;GPR146;GPR85;GRM3;GTPBP10;GUSB;HEPACAM2;HGF;HIBADH;IFRD1;IMMP2L;INTS1;JAZF1;KCND2;KCTD7;KIAA1324L;KRIT1;LAMB1;LAMB4;LMTK2;LOC100128496;LOC100288524;LOC120824;LOC283116;LOC389493;LOC646627;LOC647589;LOC653486;LRCH4;LRRD1;MAFK;MDFIC;MEPCE;MICALL2;MNX1;MOSPD3;MTERF;NCAPG2;NOM1;NRCAM;OCM2;PCLO;PCOLCE;PDGFA;PEX1;PHKG1;PILRA;PILRB;PMS2;PNPLA8;POP7;POU6F2;PPP1R3A;PRKAR1B;PRR15;PTPRN2;PVRIG;RABGEF1;RAC1;RALA;RSPH10B;RSPH10B2;SAMD9;SAMD9L;SAP25;SBDS;SEMA3A;SEMA3D;SEMA3E;SFRP4;SHFM1;SLC26A3;SPDYE3;SRI;ST7;STAG3;STAG3L4;STARD3NL;STEAP1;STEAP2;STEAP4;TAC1;TAX1BP1;TES;TFEC;TFR2;THAP5;TMEM168;TP53TG1;TPST1;TRIL;TSC22D4;TSPAN12;TXNDC3;TYW1;UBE3C;UNCX;USP42;VIPR2;VPS41;WDR60;WIPF3;WNT2;ZCWPW1;ZFAND2A;ZNF479;ZNF679;ZNF680;ZNF716;ZNF727;ZNF735;ZNF736;ZNF804B; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes CCDC132,GNGT1;PTPRN2,PDZRN4;ST7,ACTL6B;ST7,IFNGR2;ZNF804B,KIF21A CTDB0389 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 4 Glioma Next Generation Sequencing Homo sapiens SJHGG011_D Illumina Genome Analyzer IIx or HiSeq chr10:0-91700:0;chr10:109271006-135534747:0;chr10:18231777-20080862:0;chr10:20080863-21600696:1;chr10:21600697-21600696:0;chr10:21600697-21600907:1;chr10:21600908-21600907:0;chr10:21600908-21655507:1;chr10:21655508-21655507:0;chr10:21655508-21656033:1;chr10:21656034-21656033:0;chr10:21656034-21677261:1;chr10:21677262-21677261:0;chr10:21677262-21678051:1;chr10:21678052-21678051:0;chr10:21678052-21732954:1;chr10:21732955-21732954:0;chr10:21732955-23686200:1;chr10:23686201-23690636:0;chr10:23690637-23694496:1;chr10:23694497-23697016:0;chr10:23697017-23700232:1;chr10:23700233-23700232:0;chr10:23700233-23754196:1;chr10:23754197-23754196:0;chr10:23754197-23754495:1;chr10:23754496-23754495:0;chr10:23754496-23755062:1;chr10:23755063-23755062:0;chr10:23755063-23755319:1;chr10:23755320-23756573:0;chr10:23756574-23757178:1;chr10:23757179-23757178:0;chr10:23757179-23992666:1;chr10:23992667-24030213:0;chr10:24030214-24030491:1;chr10:24030492-27421002:0;chr10:27421003-27422332:1;chr10:27422333-27422332:0;chr10:27422333-27425027:1;chr10:27425028-29265627:0;chr10:29265628-29265723:1;chr10:29265724-29265723:0;chr10:29265724-29702840:1;chr10:29702841-29702840:0;chr10:29702841-29959007:1;chr10:29959008-29959007:0;chr10:29959008-29959262:1;chr10:29959263-29959262:0;chr10:29959263-29997946:1;chr10:29997947-29997946:0;chr10:29997947-29998642:1;chr10:29998643-29998642:0;chr10:29998643-30126644:1;chr10:30126645-30137823:0;chr10:30137824-30138505:1;chr10:30138506-30138505:0;chr10:30138506-30138602:1;chr10:30138603-30138602:0;chr10:30138603-30138870:1;chr10:30138871-30138870:0;chr10:30138871-30138974:1;chr10:30138975-30138974:0;chr10:30138975-30139836:1;chr10:30139837-30139836:0;chr10:30139837-30140929:1;chr10:30140930-30140929:0;chr10:30140930-30172361:1;chr10:30172362-30172361:0;chr10:30172362-30172701:1;chr10:30172702-30172701:0;chr10:30172702-30172824:1;chr10:30172825-30172824:0;chr10:30172825-30173080:1;chr10:30173081-30173080:0;chr10:30173081-30173348:1;chr10:30173349-30173348:0;chr10:30173349-30173490:1;chr10:30173491-30173490:0;chr10:30173491-30173902:1;chr10:30173903-30173902:0;chr10:30173903-30174603:1;chr10:30174604-30174603:0;chr10:30174604-30174699:1;chr10:30174700-30174699:0;chr10:30174700-30174847:1;chr10:30174848-30174847:0;chr10:30174848-30175011:1;chr10:30175012-30175011:0;chr10:30175012-30176054:1;chr10:30176055-30179754:0;chr10:30179755-30179983:1;chr10:30179984-33196200:0;chr10:33196201-35324313:-1;chr10:35324314-35324516:0;chr10:35324517-72826600:-1;chr10:595783-18231776:1;chr10:595783-595782:0;chr10:72826601-72826600:0;chr10:72826601-79928224:-1;chr10:79928225-79928224:0;chr10:79928225-87150724:-1;chr10:87150725-109271005:-1;chr10:87150725-87150724:0;chr10:91701-595782:1;chr11:0-168400:0;chr11:120675489-120757160:0;chr11:120757161-124655875:-1;chr11:124655876-124655875:0;chr11:124655876-134946400:-1;chr11:134946401-135006516:0;chr11:168401-50783700:-1;chr11:50783701-50783700:0;chr11:50783701-70816962:-1;chr11:70816963-70817293:0;chr11:70817294-80893635:-1;chr11:80893636-80893635:0;chr11:80893636-80953861:-1;chr11:80953862-80953861:0;chr11:80953862-81599543:-1;chr11:81599544-81599543:0;chr11:81599544-81600344:-1;chr11:81600345-81600344:0;chr11:81600345-81604289:-1;chr11:81604290-81604289:0;chr11:81604290-93059795:-1;chr11:93059796-95975260:0;chr11:95975261-120675488:-1;chr12:0-60700:0;chr12:118956888-118956887:0;chr12:118956888-118956955:1;chr12:118956956-118956955:0;chr12:118956956-118957223:1;chr12:118957224-118957223:0;chr12:118957224-128493888:-1;chr12:128493889-128493888:0;chr12:128493889-128644643:-1;chr12:128644644-128644643:0;chr12:128644644-131953000:-1;chr12:131953001-133851895:0;chr12:29742801-29742800:0;chr12:29742801-29798022:1;chr12:29798023-29798022:0;chr12:29798023-32002394:1;chr12:32002395-32002394:0;chr12:32002395-33937733:1;chr12:33937734-33937733:0;chr12:33937734-33938568:1;chr12:33938569-33938568:0;chr12:33938569-33972408:1;chr12:33972409-33972408:0;chr12:33972409-33972478:1;chr12:33972479-33972478:0;chr12:33972479-33972670:1;chr12:33972671-33972670:0;chr12:33972671-33972801:1;chr12:33972802-33972801:0;chr12:33972802-33972944:1;chr12:33972945-33972944:0;chr12:33972945-33974295:1;chr12:33974296-33974295:0;chr12:33974296-33974590:1;chr12:33974591-33974590:0;chr12:33974591-34798756:1;chr12:34798757-59653292:0;chr12:59653293-59675519:1;chr12:59675520-68877085:0;chr12:60701-29742800:-1;chr12:68877086-69048633:-1;chr12:69048634-69049600:0;chr12:69049601-69103937:-1;chr12:69103938-69105671:0;chr12:69105672-69110476:-1;chr12:69110477-70740404:0;chr12:70740405-71067382:-1;chr12:71067383-71341744:0;chr12:71341745-71803836:-1;chr12:71803837-71816742:0;chr12:71816743-118956887:-1;chr13:0-19125100:0;chr13:115109801-115169878:0;chr13:19125101-20098200:1;chr13:20098201-20098300:0;chr13:20098301-20118079:-1;chr13:20118080-20118079:0;chr13:20118080-20154935:1;chr13:20154936-20154935:0;chr13:20154936-20459570:-1;chr13:20459571-20459570:0;chr13:20459571-20469156:-1;chr13:20469157-20469156:0;chr13:20469157-22287219:-1;chr13:22287220-22287219:0;chr13:22287220-22289529:1;chr13:22289530-22289529:0;chr13:22289530-22290120:1;chr13:22290121-22290120:0;chr13:22290121-22290855:1;chr13:22290856-22290855:0;chr13:22290856-22366029:-1;chr13:22366030-22366029:0;chr13:22366030-23977581:1;chr13:23977582-23977581:0;chr13:23977582-24169900:-1;chr13:24169901-24170200:0;chr13:24170201-24179419:1;chr13:24179420-24179419:0;chr13:24179420-27309906:-1;chr13:27309907-27309906:0;chr13:27309907-27310414:1;chr13:27310415-27310414:0;chr13:27310415-28280300:-1;chr13:28280301-28280300:0;chr13:28280301-28558488:-1;chr13:28558489-28558488:0;chr13:28558489-41603386:-1;chr13:41603387-41603386:0;chr13:41603387-44115151:-1;chr13:44115152-44115151:0;chr13:44115152-44389921:-1;chr13:44389922-44389921:0;chr13:44389922-44455499:-1;chr13:44455500-44455499:0;chr13:44455500-44461319:-1;chr13:44461320-44461319:0;chr13:44461320-44609779:-1;chr13:44609780-44609779:0;chr13:44609780-48324958:-1;chr13:48324959-48324958:0;chr13:48324959-48949459:-1;chr13:48949460-48949459:0;chr13:48949460-54219257:-1;chr13:54219258-54219257:0;chr13:54219258-54220099:-1;chr13:54220100-54220099:0;chr13:54220100-56015997:-1;chr13:56015998-56015997:0;chr13:56015998-62752217:-1;chr13:62752218-62752217:0;chr13:62752218-66187725:-1;chr13:66187726-66187725:0;chr13:66187726-70451918:-1;chr13:70451919-70451918:0;chr13:70451919-77810900:-1;chr13:77810901-77810900:0;chr13:77810901-81583820:-1;chr13:81583821-81583820:0;chr13:81583821-81595277:-1;chr13:81595278-81595277:0;chr13:81595278-83971919:-1;chr13:83971920-83971919:0;chr13:83971920-84033970:-1;chr13:84033971-84033970:0;chr13:84033971-87464479:-1;chr13:87464480-87464479:0;chr13:87464480-90215000:-1;chr13:90215001-90215000:0;chr13:90215001-90252124:-1;chr13:90252125-90252124:0;chr13:90252125-90360138:-1;chr13:90360139-90360138:0;chr13:90360139-91202707:-1;chr13:91202708-91202707:0;chr13:91202708-91486569:-1;chr13:91486570-91486569:0;chr13:91486570-92805015:-1;chr13:92805016-92805015:0;chr13:92805016-93489175:-1;chr13:93489176-93589810:0;chr13:93589811-93593030:-1;chr13:93593031-95084298:0;chr13:95084299-115109800:-1;chr14:0-19264600:0;chr14:107289501-107349540:0;chr14:19264601-20456396:-1;chr14:20456397-20456396:0;chr14:20456397-22683200:-1;chr14:22683201-24930558:0;chr14:24930559-32573940:-1;chr14:32573941-32573940:0;chr14:32573941-32583100:-1;chr14:32583101-32583200:0;chr14:32583201-92366956:-1;chr14:92366957-92366956:0;chr14:92366957-92381398:-1;chr14:92381399-92381398:0;chr14:92381399-94218600:-1;chr14:94218601-94218600:0;chr14:94218601-94256100:-1;chr14:94256101-107289500:-1;chr14:94256101-94256100:0;chr15:0-20000000:0;chr15:20000001-24179323:-1;chr15:24179324-33390991:0;chr15:33390992-49129879:-1;chr15:49129880-49544852:0;chr15:49544853-61841464:-1;chr15:61841465-62478681:0;chr15:62478682-65514570:-1;chr15:65514571-66769417:0;chr15:66769418-68499962:-1;chr15:68499963-68499962:0;chr15:68499963-68500112:1;chr15:68500113-68500112:0;chr15:68500113-68500200:1;chr15:68500201-68500200:0;chr15:68500201-68500676:1;chr15:68500677-68500676:0;chr15:68500677-81768972:-1;chr15:81768973-81768972:0;chr15:81768973-81772164:-1;chr15:81772165-81772164:0;chr15:81772165-90119500:-1;chr15:90119501-90119500:0;chr15:90119501-90625575:-1;chr15:90625576-94344952:0;chr15:94344953-94346056:1;chr15:94346057-94346056:0;chr15:94346057-95016378:-1;chr15:95016379-95175958:0;chr15:95175959-95377821:-1;chr15:95377822-102531392:0;chr16:0-83600:0;chr16:33964801-34190006:0;chr16:34190007-58242423:-1;chr16:58242424-58242423:0;chr16:58242424-69016558:-1;chr16:69016559-69018202:0;chr16:69018203-69024689:-1;chr16:69024690-69024689:0;chr16:69024690-69688838:-1;chr16:69688839-69688838:0;chr16:69688839-69972300:1;chr16:69972301-70152000:0;chr16:70152001-70358332:-1;chr16:70358333-71096000:0;chr16:71096001-71330182:-1;chr16:71330183-71330182:0;chr16:71330183-71562127:-1;chr16:71562128-71562127:0;chr16:71562128-73875600:-1;chr16:73875601-73875600:0;chr16:73875601-87514543:-1;chr16:83601-33964800:-1;chr16:87514544-87514543:0;chr16:87514544-87532502:-1;chr16:87532503-87532502:0;chr16:87532503-90168500:-1;chr16:90168501-90354753:0;chr17:0-896000:0;chr17:21231836-21231835:0;chr17:21231836-22045800:-1;chr17:22045801-28677308:0;chr17:28677309-28714557:-1;chr17:28714558-28730204:0;chr17:28730205-41217781:-1;chr17:41217782-42712500:0;chr17:42712501-46671495:-1;chr17:46671496-46766434:0;chr17:46766435-46782941:-1;chr17:46782942-46782941:0;chr17:46782942-46795292:1;chr17:46795293-46795292:0;chr17:46795293-46795972:1;chr17:46795973-46795972:0;chr17:46795973-51301020:1;chr17:51301021-51301020:0;chr17:51301021-53098878:-1;chr17:53098879-53410431:0;chr17:53410432-55329374:1;chr17:55329375-57929876:0;chr17:57929877-57941463:1;chr17:57941464-57941463:0;chr17:57941464-58357400:1;chr17:58357401-58357671:0;chr17:58357672-61596055:-1;chr17:61596056-61596055:0;chr17:61596056-66851332:-1;chr17:66851333-67173030:0;chr17:67173031-74545895:-1;chr17:74545896-74545895:0;chr17:74545896-74803597:-1;chr17:74803598-81195210:0;chr17:896001-21231835:-1;chr18:0-65854094:0;chr18:65854095-78017200:-1;chr18:78017201-78077248:0;chr19:0-17958800:0;chr19:17958801-17977217:1;chr19:17977218-29058557:0;chr19:29058558-29290985:-1;chr19:29290986-29291363:0;chr19:29291364-37316083:-1;chr19:37316084-37316431:0;chr19:37316432-43984638:-1;chr19:43984639-57922927:0;chr19:57922928-57924666:-1;chr19:57924667-57937568:0;chr19:57937569-58359000:-1;chr19:58359001-58582700:0;chr19:58582701-59097500:-1;chr19:59097501-59128983:0;chr1:0-1348200:0;chr1:100636097-100636384:0;chr1:100636385-103028342:-1;chr1:103028343-103028800:0;chr1:103028801-103029039:1;chr1:103029040-103029039:0;chr1:103029040-103029100:1;chr1:103029101-103029100:0;chr1:103029101-103222507:-1;chr1:103222508-103222507:0;chr1:103222508-103222627:1;chr1:103222628-103222627:0;chr1:103222628-103222745:1;chr1:103222746-103222788:0;chr1:103222789-104030738:-1;chr1:104030739-104030816:0;chr1:104030817-104031016:1;chr1:104031017-104031016:0;chr1:104031017-104031291:1;chr1:104031292-104031291:0;chr1:104031292-104031520:1;chr1:104031521-104031520:0;chr1:104031521-104031837:1;chr1:104031838-104031837:0;chr1:104031838-104032095:1;chr1:104032096-104032095:0;chr1:104032096-104032402:1;chr1:104032403-104032457:0;chr1:104032458-104118999:-1;chr1:104119000-104119514:0;chr1:104119515-121387100:-1;chr1:11538433-13727300:0;chr1:121387101-147393300:0;chr1:1348201-1349367:1;chr1:1349368-1349367:0;chr1:1349368-1350400:-1;chr1:1350401-1350474:0;chr1:1350475-1388300:-1;chr1:13727301-25768006:-1;chr1:1388301-1391123:0;chr1:1391124-5995188:-1;chr1:147393301-147393600:1;chr1:147393601-149029498:0;chr1:149029499-156292697:-1;chr1:156292698-156390119:0;chr1:156390120-159918702:-1;chr1:159918703-159918702:0;chr1:159918703-159919758:1;chr1:159919759-160198300:0;chr1:160198301-165169623:-1;chr1:165169624-165273007:0;chr1:165273008-165858683:-1;chr1:165858684-166027982:0;chr1:166027983-166857362:-1;chr1:166857363-167891505:0;chr1:167891506-172094388:-1;chr1:172094389-172094936:0;chr1:172094937-172095487:-1;chr1:172095488-172095971:0;chr1:172095972-172133763:-1;chr1:172133764-172134215:0;chr1:172134216-172148356:-1;chr1:172148357-172556829:0;chr1:172556830-172884500:-1;chr1:172884501-172884733:0;chr1:172884734-172885283:1;chr1:172885284-172885283:0;chr1:172885284-172885370:1;chr1:172885371-172885803:0;chr1:172885804-172900688:-1;chr1:172900689-172900867:0;chr1:172900868-173388904:-1;chr1:173388905-185276822:0;chr1:185276823-185276900:-1;chr1:185276901-185276900:0;chr1:185276901-185280436:-1;chr1:185280437-185280436:0;chr1:185280437-188947288:-1;chr1:188947289-188947288:0;chr1:188947289-188995919:-1;chr1:188995920-188995919:0;chr1:188995920-208320771:-1;chr1:208320772-208320771:0;chr1:208320772-209898055:-1;chr1:209898056-209898055:0;chr1:209898056-213697717:-1;chr1:213697718-213697717:0;chr1:213697718-214862687:-1;chr1:214862688-214862687:0;chr1:214862688-242924852:-1;chr1:242924853-243067902:0;chr1:243067903-243075100:-1;chr1:243075101-243075699:0;chr1:243075700-249240500:-1;chr1:249240501-249250621:0;chr1:25768007-26854689:0;chr1:26854690-32228184:-1;chr1:32228185-32228184:0;chr1:32228185-32228359:1;chr1:32228360-32228359:0;chr1:32228360-58002303:-1;chr1:58002304-63532697:0;chr1:5995189-5995188:0;chr1:5995189-5995616:1;chr1:5995617-5995616:0;chr1:5995617-6000461:-1;chr1:6000462-6005159:0;chr1:6005160-7915970:-1;chr1:63532698-70820632:-1;chr1:70820633-70901844:0;chr1:70901845-70901865:1;chr1:70901866-70901865:0;chr1:70901866-70902069:1;chr1:70902070-70902069:0;chr1:70902070-70902182:1;chr1:70902183-70902182:0;chr1:70902183-70902277:1;chr1:70902278-70902277:0;chr1:70902278-70902394:1;chr1:70902395-70910674:0;chr1:70910675-70910891:1;chr1:70910892-70910891:0;chr1:70910892-70911028:1;chr1:70911029-70911363:0;chr1:70911364-70912779:-1;chr1:70912780-70912779:0;chr1:70912780-70912875:1;chr1:70912876-70912875:0;chr1:70912876-70913130:1;chr1:70913131-70913130:0;chr1:70913131-70913486:1;chr1:70913487-70913486:0;chr1:70913487-70929732:-1;chr1:70929733-70929732:0;chr1:70929733-70929800:1;chr1:70929801-70929800:0;chr1:70929801-70930005:1;chr1:70930006-70930005:0;chr1:70930006-70930071:1;chr1:70930072-70930071:0;chr1:70930072-74794907:-1;chr1:74794908-74858925:0;chr1:74858926-77161847:-1;chr1:77161848-77161847:0;chr1:77161848-77172616:-1;chr1:77172617-85296877:0;chr1:7915971-9101642:0;chr1:85296878-85297018:1;chr1:85297019-85297018:0;chr1:85297019-85297200:1;chr1:85297201-85297401:0;chr1:85297402-85302219:-1;chr1:85302220-85302219:0;chr1:85302220-85302588:1;chr1:85302589-85302588:0;chr1:85302589-85302926:1;chr1:85302927-85302926:0;chr1:85302927-85302962:1;chr1:85302963-85302962:0;chr1:85302963-87206079:-1;chr1:87206080-87206079:0;chr1:87206080-87206430:1;chr1:87206431-87206430:0;chr1:87206431-87237842:-1;chr1:87237843-87237842:0;chr1:87237843-87238233:1;chr1:87238234-87238233:0;chr1:87238234-87277335:-1;chr1:87277336-87277335:0;chr1:87277336-87277510:1;chr1:87277511-87277510:0;chr1:87277511-87327182:-1;chr1:87327183-87327182:0;chr1:87327183-87327321:1;chr1:87327322-87327321:0;chr1:87327322-91143416:-1;chr1:9101643-9357739:-1;chr1:91143417-91143416:0;chr1:91143417-91143462:1;chr1:91143463-91143462:0;chr1:91143463-91143745:1;chr1:91143746-91143745:0;chr1:91143746-91156576:-1;chr1:91156577-91156576:0;chr1:91156577-91156871:1;chr1:91156872-91156871:0;chr1:91156872-93367731:-1;chr1:93367732-93367964:0;chr1:93367965-93378417:-1;chr1:93378418-93378502:0;chr1:93378503-93378604:1;chr1:93378605-93378604:0;chr1:93378605-93378735:1;chr1:93378736-93378735:0;chr1:93378736-93378974:1;chr1:93378975-93378974:0;chr1:93378975-93379093:1;chr1:93379094-93379093:0;chr1:93379094-93379167:1;chr1:93379168-93379167:0;chr1:93379168-93379358:1;chr1:93379359-93379358:0;chr1:93379359-93379615:1;chr1:93379616-93379615:0;chr1:93379616-93395039:-1;chr1:93395040-93395093:0;chr1:93395094-93395728:1;chr1:93395729-93395728:0;chr1:93395729-93395881:1;chr1:93395882-93395962:0;chr1:93395963-93413928:-1;chr1:93413929-93414209:0;chr1:93414210-93498482:-1;chr1:93498483-93498482:0;chr1:93498483-93498986:1;chr1:93498987-93498986:0;chr1:93498987-93528500:-1;chr1:93528501-93528500:0;chr1:93528501-93528640:1;chr1:93528641-93528640:0;chr1:93528641-93528821:1;chr1:93528822-93528821:0;chr1:93528822-93528892:1;chr1:93528893-93529039:0;chr1:93529040-93529100:1;chr1:93529101-93529300:0;chr1:93529301-93529371:1;chr1:93529372-93529371:0;chr1:93529372-93529462:1;chr1:93529463-93529462:0;chr1:93529463-93529643:1;chr1:93529644-93529643:0;chr1:93529644-93529695:1;chr1:93529696-93529877:0;chr1:93529878-93533209:-1;chr1:93533210-93533277:0;chr1:93533278-93533449:1;chr1:93533450-93533449:0;chr1:93533450-93533543:1;chr1:93533544-93533543:0;chr1:93533544-93533644:1;chr1:93533645-93533644:0;chr1:93533645-93533928:1;chr1:93533929-93533928:0;chr1:93533929-93534282:-1;chr1:93534283-93534282:0;chr1:93534283-93534445:1;chr1:93534446-93534445:0;chr1:93534446-93534462:1;chr1:93534463-100636096:-1;chr1:93534463-93534462:0;chr1:9357740-9357820:0;chr1:9357821-9358171:1;chr1:9358172-9358171:0;chr1:9358172-9358447:1;chr1:9358448-11538432:-1;chr1:9358448-9358447:0;chr20:0-63025520:0;chr21:0-14589800:0;chr21:14589801-14590300:-1;chr21:14590301-15200800:0;chr21:15200801-23170922:-1;chr21:23170923-23170922:0;chr21:23170923-48119800:-1;chr21:48119801-48129895:0;chr22:0-51304566:0;chr2:0-14385:0;chr2:10197346-71459210:0;chr2:14386-15062:1;chr2:15063-2898195:0;chr2:213446296-213446295:0;chr2:213446296-217685212:-1;chr2:217685213-217685212:0;chr2:217685213-225300000:-1;chr2:225300001-225300059:0;chr2:225300060-243183600:-1;chr2:243183601-243199373:0;chr2:2898196-5221211:-1;chr2:5221212-8221106:0;chr2:71459211-71459253:-1;chr2:71459254-71819863:0;chr2:71819864-80891575:-1;chr2:80891576-80891575:0;chr2:80891576-84098201:-1;chr2:8221107-8686812:1;chr2:84098202-84098201:0;chr2:84098202-86243924:-1;chr2:86243925-86245504:0;chr2:86245505-90021600:-1;chr2:8686813-9139704:0;chr2:90021601-95328000:0;chr2:9139705-10197345:-1;chr2:95328001-213446295:-1;chr3:0-60200:0;chr3:10031201-11150396:1;chr3:101383422-101399648:0;chr3:101399649-102654095:1;chr3:102654096-102654511:0;chr3:102654512-103049607:1;chr3:103049608-103049607:0;chr3:103049608-106590500:-1;chr3:106590501-106590800:0;chr3:106590801-116564343:-1;chr3:11150397-11937300:0;chr3:116564344-116564343:0;chr3:116564344-117369739:-1;chr3:117369740-117369739:0;chr3:117369740-123626364:-1;chr3:11937301-11999858:1;chr3:11999859-11999858:0;chr3:11999859-12006064:1;chr3:12006065-12006064:0;chr3:12006065-12006546:1;chr3:12006547-12006690:0;chr3:12006691-12006970:1;chr3:12006971-12008811:0;chr3:12008812-12019893:1;chr3:12019894-12029256:0;chr3:12029257-12049778:1;chr3:12049779-12053354:0;chr3:12053355-12583814:1;chr3:123626365-123626364:0;chr3:123626365-138837900:-1;chr3:12583815-12583814:0;chr3:12583815-14120342:1;chr3:138837901-138837900:0;chr3:138837901-138845036:-1;chr3:138845037-138845433:0;chr3:138845434-138845970:-1;chr3:138845971-138845970:0;chr3:138845971-138852435:-1;chr3:138852436-138852435:0;chr3:138852436-138853772:-1;chr3:138853773-138853772:0;chr3:138853773-138854198:-1;chr3:138854199-138854198:0;chr3:138854199-160669929:-1;chr3:14120343-14120342:0;chr3:14120343-14999954:1;chr3:14999955-14999954:0;chr3:14999955-15004117:1;chr3:15004118-15004117:0;chr3:15004118-15004587:1;chr3:15004588-15004587:0;chr3:15004588-15008063:1;chr3:15008064-15008063:0;chr3:15008064-15021010:1;chr3:15021011-15021010:0;chr3:15021011-15197162:1;chr3:15197163-15197162:0;chr3:15197163-15203221:1;chr3:15203222-15203221:0;chr3:15203222-15221353:1;chr3:15221354-15221353:0;chr3:15221354-15284289:1;chr3:15284290-15284289:0;chr3:15284290-15287824:1;chr3:15287825-15287824:0;chr3:15287825-15290040:1;chr3:15290041-15290040:0;chr3:15290041-15290794:1;chr3:15290795-15290794:0;chr3:15290795-16292009:1;chr3:160669930-160669929:0;chr3:160669930-160689212:-1;chr3:160689213-160689212:0;chr3:160689213-160991094:-1;chr3:160991095-160991094:0;chr3:160991095-161004252:-1;chr3:161004253-161004252:0;chr3:161004253-161010147:-1;chr3:161010148-161010147:0;chr3:161010148-161014655:-1;chr3:161014656-161014655:0;chr3:161014656-161033633:-1;chr3:161033634-161033633:0;chr3:161033634-161039381:-1;chr3:161039382-161039381:0;chr3:161039382-165213958:-1;chr3:16292010-16292009:0;chr3:16292010-16298807:-1;chr3:16298808-16298807:0;chr3:16298808-16299116:1;chr3:16299117-16299116:0;chr3:16299117-16307865:-1;chr3:16307866-16308080:0;chr3:16308081-30401030:-1;chr3:165213959-165213958:0;chr3:165213959-165214230:-1;chr3:165214231-165214230:0;chr3:165214231-165218478:-1;chr3:165218479-165218478:0;chr3:165218479-165222543:-1;chr3:165222544-165222543:0;chr3:165222544-165433356:-1;chr3:165433357-165433356:0;chr3:165433357-166601226:-1;chr3:166601227-166601226:0;chr3:166601227-166625100:1;chr3:166625101-166625400:0;chr3:166625401-166652455:1;chr3:166652456-166652455:0;chr3:166652456-167140258:1;chr3:167140259-167140258:0;chr3:167140259-167142000:1;chr3:167142001-167142500:0;chr3:167142501-167259276:1;chr3:167259277-167259276:0;chr3:167259277-167845797:-1;chr3:167845798-167845797:0;chr3:167845798-167874738:-1;chr3:167874739-167874738:0;chr3:167874739-168641100:-1;chr3:168641101-168641100:0;chr3:168641101-170784202:-1;chr3:170784203-170795104:0;chr3:170795105-170795473:1;chr3:170795474-170795473:0;chr3:170795474-170803582:-1;chr3:170803583-177882100:0;chr3:177882101-178367572:1;chr3:178367573-178367572:0;chr3:178367573-178605855:1;chr3:178605856-178605855:0;chr3:178605856-178740269:1;chr3:178740270-178740269:0;chr3:178740270-178778907:1;chr3:178778908-178793881:0;chr3:178793882-178810941:1;chr3:178810942-179021936:0;chr3:179021937-179050036:1;chr3:179050037-179050759:0;chr3:179050760-179288352:1;chr3:179288353-180623798:0;chr3:180623799-180624013:1;chr3:180624014-180624013:0;chr3:180624014-180624530:1;chr3:180624531-180624530:0;chr3:180624531-180624600:1;chr3:180624601-180978189:0;chr3:180978190-180978406:1;chr3:180978407-180995609:0;chr3:180995610-180996010:1;chr3:180996011-180997983:0;chr3:180997984-182060485:1;chr3:182060486-182229182:0;chr3:182229183-182229957:1;chr3:182229958-182229957:0;chr3:182229958-182260641:1;chr3:182260642-182267717:0;chr3:182267718-182428140:1;chr3:182428141-183855743:0;chr3:183855744-183910435:1;chr3:183910436-184087366:0;chr3:184087367-184638011:1;chr3:184638012-185614616:0;chr3:185614617-185615565:1;chr3:185615566-185615565:0;chr3:185615566-185616189:1;chr3:185616190-190514110:0;chr3:190514111-194398681:1;chr3:194398682-194398681:0;chr3:194398682-194400290:-1;chr3:194400291-194400290:0;chr3:194400291-194733784:1;chr3:194733785-194735909:0;chr3:194735910-195109487:1;chr3:195109488-195167299:0;chr3:195167300-195276100:1;chr3:195276101-195276100:0;chr3:195276101-195285230:1;chr3:195285231-198022430:0;chr3:2329124-2329123:0;chr3:2329124-4686443:-1;chr3:30401031-30401030:0;chr3:30401031-30863318:-1;chr3:30863319-30863318:0;chr3:30863319-35064654:-1;chr3:35064655-35064654:0;chr3:35064655-35797096:1;chr3:35797097-36002585:0;chr3:36002586-71640057:-1;chr3:4686444-4686443:0;chr3:4686444-4686609:-1;chr3:4686610-4686931:0;chr3:4686932-4687164:-1;chr3:4687165-4687164:0;chr3:4687165-4687481:1;chr3:4687482-4687481:0;chr3:4687482-4693378:-1;chr3:4693379-4693378:0;chr3:4693379-4694571:1;chr3:4694572-4694571:0;chr3:4694572-4694738:1;chr3:4694739-4694738:0;chr3:4694739-4694873:1;chr3:4694874-4694873:0;chr3:4694874-4694992:1;chr3:4694993-4695088:0;chr3:4695089-4695391:1;chr3:4695392-4700294:0;chr3:4700295-4703504:1;chr3:4703505-4736030:0;chr3:4736031-5489733:-1;chr3:540692-540691:0;chr3:540692-541477:1;chr3:541478-541477:0;chr3:541478-542209:-1;chr3:542210-542209:0;chr3:542210-543271:-1;chr3:543272-2329123:-1;chr3:543272-543271:0;chr3:5489734-5489733:0;chr3:5489734-5845300:1;chr3:5845301-5845600:0;chr3:5845601-5846627:1;chr3:5846628-5846627:0;chr3:5846628-5945331:-1;chr3:5945332-5945331:0;chr3:5945332-5974163:1;chr3:5974164-5974163:0;chr3:5974164-6970434:-1;chr3:60201-540691:-1;chr3:6970435-6970434:0;chr3:6970435-7465692:1;chr3:71640058-71640057:0;chr3:71640058-72549306:-1;chr3:72549307-72549306:0;chr3:72549307-72549402:-1;chr3:72549403-72549402:0;chr3:72549403-72550104:-1;chr3:72550105-72550104:0;chr3:72550105-72550875:1;chr3:72550876-72550875:0;chr3:72550876-72554500:-1;chr3:72554501-72554500:0;chr3:72554501-72555045:-1;chr3:72555046-72555045:0;chr3:72555046-72569664:1;chr3:72569665-72569664:0;chr3:72569665-78507936:-1;chr3:7465693-8587348:0;chr3:78507937-78507936:0;chr3:78507937-78813178:1;chr3:78813179-78813178:0;chr3:78813179-78816200:-1;chr3:78816201-78816300:0;chr3:78816301-79479663:1;chr3:79479664-79481663:0;chr3:79481664-79481764:1;chr3:79481765-79481764:0;chr3:79481765-81808838:-1;chr3:81808839-82115651:0;chr3:82115652-82411412:1;chr3:82411413-82411955:0;chr3:82411956-82416343:1;chr3:82416344-82416343:0;chr3:82416344-82416897:1;chr3:82416898-82416897:0;chr3:82416898-82435318:1;chr3:82435319-82435318:0;chr3:82435319-82476035:-1;chr3:82476036-82483304:0;chr3:82483305-82495991:-1;chr3:82495992-82624888:0;chr3:82624889-84433760:-1;chr3:84433761-84433760:0;chr3:84433761-86163143:-1;chr3:8587349-8678233:1;chr3:86163144-86163143:0;chr3:86163144-86737861:-1;chr3:86737862-86749113:0;chr3:86749114-86785148:-1;chr3:8678234-10031200:0;chr3:86785149-86785148:0;chr3:86785149-86823886:-1;chr3:86823887-86823886:0;chr3:86823887-88777257:-1;chr3:88777258-101383421:-1;chr3:88777258-88777257:0;chr4:0-68700:0;chr4:128974-128973:0;chr4:128974-1367075:-1;chr4:1367076-1367075:0;chr4:1367076-22027005:-1;chr4:169486710-169486709:0;chr4:169486710-173858854:-1;chr4:173858855-173858854:0;chr4:173858855-177686229:-1;chr4:177686230-177689033:0;chr4:177689034-177690173:1;chr4:177690174-177690580:0;chr4:177690581-177690880:1;chr4:177690881-177690980:0;chr4:177690981-178317766:-1;chr4:178317767-178317766:0;chr4:178317767-189725792:-1;chr4:189725793-189725792:0;chr4:189725793-190987600:-1;chr4:190987601-191154276:0;chr4:22027006-22027005:0;chr4:22027006-22027104:1;chr4:22027105-22027104:0;chr4:22027105-22027155:1;chr4:22027156-22027155:0;chr4:22027156-22027298:1;chr4:22027299-22027298:0;chr4:22027299-22027421:1;chr4:22027422-22027421:0;chr4:22027422-22027528:1;chr4:22027529-22027528:0;chr4:22027529-22032609:-1;chr4:22032610-22032609:0;chr4:22032610-22037500:1;chr4:22037501-22038100:0;chr4:22038101-22833332:-1;chr4:22833333-24572569:0;chr4:24572570-24577614:-1;chr4:24577615-24976978:0;chr4:24976979-25120539:1;chr4:25120540-25645833:0;chr4:25645834-25646684:-1;chr4:25646685-26878485:0;chr4:26878486-26878874:-1;chr4:26878875-40921576:0;chr4:40921577-40941277:1;chr4:40941278-41668852:0;chr4:41668853-43132783:-1;chr4:43132784-43132783:0;chr4:43132784-44468908:-1;chr4:44468909-44468908:0;chr4:44468909-46655070:-1;chr4:46655071-46655070:0;chr4:46655071-49092500:-1;chr4:49092501-52680900:0;chr4:52680901-53862570:1;chr4:53862571-53862570:0;chr4:53862571-54361833:1;chr4:54361834-54361833:0;chr4:54361834-54361928:1;chr4:54361929-54361928:0;chr4:54361929-54365728:1;chr4:54365729-54365728:0;chr4:54365729-54486333:1;chr4:54486334-54486333:0;chr4:54486334-54487441:1;chr4:54487442-54487441:0;chr4:54487442-54709933:1;chr4:54709934-54709933:0;chr4:54709934-54709980:1;chr4:54709981-54709980:0;chr4:54709981-54710655:1;chr4:54710656-54710655:0;chr4:54710656-54711580:1;chr4:54711581-54711580:0;chr4:54711581-54711865:1;chr4:54711866-54711865:0;chr4:54711866-71497946:-1;chr4:68701-128973:-1;chr4:71497947-71497946:0;chr4:71497947-82167981:-1;chr4:82167982-82168187:0;chr4:82168188-82377307:-1;chr4:82377308-85007539:0;chr4:85007540-85008799:-1;chr4:85008800-85059413:0;chr4:85059414-85459105:1;chr4:85459106-85459105:0;chr4:85459106-85608248:1;chr4:85608249-85608248:0;chr4:85608249-85758625:1;chr4:85758626-85758625:0;chr4:85758626-86333502:-1;chr4:86333503-87367360:0;chr4:87367361-98086467:-1;chr4:98086468-98086467:0;chr4:98086468-98106322:1;chr4:98106323-98106322:0;chr4:98106323-98112400:1;chr4:98112401-98112400:0;chr4:98112401-98194400:1;chr4:98194401-98195400:0;chr4:98195401-98315483:1;chr4:98315484-98315483:0;chr4:98315484-98797872:-1;chr4:98797873-98797872:0;chr4:98797873-98874173:1;chr4:98874174-98874173:0;chr4:98874174-98877585:1;chr4:98877586-98877585:0;chr4:98877586-98896508:-1;chr4:98896509-98896508:0;chr4:98896509-98896782:1;chr4:98896783-98896782:0;chr4:98896783-98899420:-1;chr4:98899421-98899420:0;chr4:98899421-99029366:1;chr4:99029367-169486709:-1;chr4:99029367-99029366:0;chr5:0-11700:0;chr5:11701-50321833:-1;chr5:162855469-162855468:0;chr5:162855469-163856666:-1;chr5:163856667-163856666:0;chr5:163856667-163858162:-1;chr5:163858163-163858162:0;chr5:163858163-180736100:-1;chr5:180736101-180915260:0;chr5:50321834-50321833:0;chr5:50321834-50401381:-1;chr5:50401382-50401381:0;chr5:50401382-52099744:-1;chr5:52099745-52113297:0;chr5:52113298-52122477:-1;chr5:52122478-65384384:0;chr5:65384385-65397063:1;chr5:65397064-65397063:0;chr5:65397064-65397318:1;chr5:65397319-65397318:0;chr5:65397319-65397742:1;chr5:65397743-65397742:0;chr5:65397743-65416494:1;chr5:65416495-65416494:0;chr5:65416495-72209700:1;chr5:72209701-72209700:0;chr5:72209701-72209800:1;chr5:72209801-72210124:0;chr5:72210125-72211000:1;chr5:72211001-72211000:0;chr5:72211001-72317595:1;chr5:72317596-72317595:0;chr5:72317596-72366553:1;chr5:72366554-74443543:0;chr5:74443544-74444808:1;chr5:74444809-74980984:0;chr5:74980985-74982200:1;chr5:74982201-75520192:0;chr5:75520193-79265805:1;chr5:79265806-79265805:0;chr5:79265806-79358295:1;chr5:79358296-79358295:0;chr5:79358296-86762900:1;chr5:86762901-86763047:0;chr5:86763048-86763365:1;chr5:86763366-86785948:0;chr5:86785949-86785954:1;chr5:86785955-86785954:0;chr5:86785955-86786262:1;chr5:86786263-86786262:0;chr5:86786263-86786519:1;chr5:86786520-86786519:0;chr5:86786520-92896065:1;chr5:92896066-162855468:-1;chr5:92896066-92896065:0;chr6:0-90700:0;chr6:105437995-105608884:0;chr6:105608885-118348128:-1;chr6:118348129-118348128:0;chr6:118348129-118362975:-1;chr6:118362976-118362975:0;chr6:118362976-120729259:-1;chr6:120729260-122536651:0;chr6:122536652-149351780:-1;chr6:149351781-149351780:0;chr6:149351781-149351977:-1;chr6:149351978-149351977:0;chr6:149351978-162605039:-1;chr6:162605040-168689326:0;chr6:168689327-168916394:1;chr6:168916395-169287421:0;chr6:169287422-170911800:1;chr6:170911801-171115067:0;chr6:17302201-17302200:0;chr6:17302201-17302474:-1;chr6:17302475-17302474:0;chr6:17302475-17747608:-1;chr6:17747609-17747608:0;chr6:17747609-17747904:-1;chr6:17747905-105437994:-1;chr6:17747905-17747904:0;chr6:90701-17302200:-1;chr7:0-198679:0;chr7:119535801-119536716:1;chr7:119536717-119536716:0;chr7:119536717-120191377:1;chr7:120191378-120191377:0;chr7:120191378-121631717:1;chr7:121631718-121631717:0;chr7:121631718-121686995:1;chr7:121686996-121686995:0;chr7:121686996-121865547:1;chr7:121865548-131921178:0;chr7:131921179-131921400:1;chr7:131921401-159138663:0;chr7:19453389-19473282:0;chr7:19473283-20969615:-1;chr7:198680-199486:1;chr7:199487-199486:0;chr7:199487-199748:1;chr7:199749-5580795:0;chr7:20969616-20978089:0;chr7:20978090-22410977:-1;chr7:22410978-22422758:0;chr7:22422759-22426434:-1;chr7:22426435-22449203:0;chr7:22449204-66569381:-1;chr7:5580796-19453388:-1;chr7:66569382-66569381:0;chr7:66569382-68005687:1;chr7:68005688-119535800:0;chr8:0-100700:0;chr8:100701-24107372:-1;chr8:24107373-38487094:0;chr8:38487095-38487558:-1;chr8:38487559-48454757:0;chr8:48454758-69119903:1;chr8:69119904-69119903:0;chr8:69119904-69120018:-1;chr8:69120019-76948637:0;chr8:76948638-76949018:1;chr8:76949019-77021507:0;chr8:77021508-82597329:-1;chr8:82597330-82597329:0;chr8:82597330-82627826:-1;chr8:82627827-82627826:0;chr8:82627827-82660500:-1;chr8:82660501-82660800:0;chr8:82660801-85695365:-1;chr8:85695366-146364022:0;chr9:0-1125314:0;chr9:10076887-10076886:0;chr9:10076887-10129910:-1;chr9:10129911-10129910:0;chr9:10129911-11302835:1;chr9:1125315-6567675:-1;chr9:112663961-116648704:1;chr9:11302836-11302835:0;chr9:11302836-11307688:1;chr9:11307689-11307688:0;chr9:11307689-11338915:1;chr9:11338916-11338915:0;chr9:11338916-11914496:1;chr9:116648705-141213431:0;chr9:11914497-11929645:0;chr9:11929646-11931527:-1;chr9:11931528-11931527:0;chr9:11931528-11938245:1;chr9:11938246-11938245:0;chr9:11938246-19875640:-1;chr9:19875641-19896100:0;chr9:19896101-20128713:-1;chr9:20128714-20128713:0;chr9:20128714-20128962:1;chr9:20128963-20128962:0;chr9:20128963-20129125:1;chr9:20129126-20129125:0;chr9:20129126-20145649:-1;chr9:20145650-20145700:0;chr9:20145701-20196122:-1;chr9:20196123-20196122:0;chr9:20196123-20618910:1;chr9:20618911-20766392:0;chr9:20766393-20766560:-1;chr9:20766561-21069638:0;chr9:21069639-21631127:-1;chr9:21631128-21631127:0;chr9:21631128-23019618:-1;chr9:23019619-23019907:0;chr9:23019908-23021570:-1;chr9:23021571-26635924:0;chr9:26635925-26749880:-1;chr9:26749881-28883426:0;chr9:28883427-28883921:-1;chr9:28883922-29533136:0;chr9:29533137-29535140:1;chr9:29535141-29535172:0;chr9:29535173-29580700:1;chr9:29580701-29580700:0;chr9:29580701-31073516:1;chr9:31073517-31073516:0;chr9:31073517-31133000:1;chr9:31133001-31133200:0;chr9:31133201-31135299:1;chr9:31135300-31135299:0;chr9:31135300-31553970:1;chr9:31553971-31553970:0;chr9:31553971-35923315:1;chr9:35923316-35923315:0;chr9:35923316-35923586:1;chr9:35923587-35923586:0;chr9:35923587-36142204:1;chr9:36142205-36142204:0;chr9:36142205-36159529:1;chr9:36159530-36163031:0;chr9:36163032-36188552:1;chr9:36188553-36191166:0;chr9:36191167-36404707:1;chr9:36404708-36519696:0;chr9:36519697-36519782:1;chr9:36519783-36519782:0;chr9:36519783-36519944:1;chr9:36519945-36519944:0;chr9:36519945-36520068:1;chr9:36520069-36520068:0;chr9:36520069-36520160:1;chr9:36520161-36520160:0;chr9:36520161-36678661:1;chr9:36678662-36678661:0;chr9:36678662-37979988:-1;chr9:37979989-37979988:0;chr9:37979989-37998843:1;chr9:37998844-37998843:0;chr9:37998844-37999305:-1;chr9:37999306-37999305:0;chr9:37999306-38063552:1;chr9:38063553-38069583:0;chr9:38069584-38467701:1;chr9:38467702-38467701:0;chr9:38467702-39183900:-1;chr9:39183901-112663960:0;chr9:6567676-6567675:0;chr9:6567676-6639500:1;chr9:6639501-8530255:0;chr9:8530256-8782553:-1;chr9:8782554-8844122:0;chr9:8844123-10076886:-1;chrX:0-2699500:0;chrX:101997363-101997362:0;chrX:101997363-102003342:-1;chrX:102003343-102003342:0;chrX:102003343-116604865:-1;chrX:116604866-116604865:0;chrX:116604866-126201500:1;chrX:126201501-130646900:0;chrX:130646901-133113988:1;chrX:133113989-133113988:0;chrX:133113989-135782300:1;chrX:135782301-155270560:0;chrX:2699501-31843000:-1;chrX:31843001-31843000:0;chrX:31843001-31944654:1;chrX:31944655-31964426:0;chrX:31964427-32065781:-1;chrX:32065782-32065781:0;chrX:32065782-32066091:1;chrX:32066092-32066091:0;chrX:32066092-42181866:-1;chrX:42181867-42181866:0;chrX:42181867-43675146:1;chrX:43675147-43675146:0;chrX:43675147-53370516:-1;chrX:53370517-56837610:0;chrX:56837611-56837700:1;chrX:56837701-57608218:0;chrX:57608219-57643587:1;chrX:57643588-57644937:0;chrX:57644938-57816527:1;chrX:57816528-57826211:0;chrX:57826212-58202889:1;chrX:58202890-58202889:0;chrX:58202890-62603795:-1;chrX:62603796-62662983:0;chrX:62662984-64560529:-1;chrX:64560530-64623933:0;chrX:64623934-64625338:-1;chrX:64625339-64721761:0;chrX:64721762-67067366:-1;chrX:67067367-67067366:0;chrX:67067367-67069661:1;chrX:67069662-67069661:0;chrX:67069662-67177191:-1;chrX:67177192-67275700:0;chrX:67275701-67512177:-1;chrX:67512178-67512720:0;chrX:67512721-68160405:-1;chrX:68160406-68386213:0;chrX:68386214-101997362:-1;chrY:0-2649500:0;chrY:23655101-59373566:0;chrY:2649501-2810700:-1;chrY:2810701-23655100:-1;chrY:2810701-2810700:0 hs1:165169624-165169624,hs19:42176073-42176073;hs1:172095972-172095972,hs19:57924667-57924667;hs1:1388284-1388284,hs1:6005160-6005160;hs1:1388284-1388284,hs1:6005160-6005160;hs1:1388284-1388284,hs1:6005160-6005160;hs1:26984900-26984900,hs1:63532698-63532698;hs1:100636097-100636097,hs2:71819232-71819232;hs1:3047208-3047208,hs21:14423538-14423538;hs1:70902066-70902066,hs1:70901950-70901950;hs1:161253591-161253591,hs7:120165566-120165566;hs1:9101643-9101643,hs21:14455432-14455432;hs1:172556830-172556830,hs7:120206744-120206744;hs1:172084615-172084615,hs7:121631718-121631718;hs1:85302589-85302589,hs1:85302220-85302220;hs1:93367732-93367732,hs1:85296904-85296904;hs1:70902040-70902040,hs1:70901845-70901845;hs1:70902040-70902040,hs1:70901845-70901845;hs1:1388284-1388284,hs1:6005160-6005160;hs1:167891506-167891506,hs19:57922928-57922928;hs1:74858926-74858926,hs10:21655577-21655577;hs1:172556830-172556830,hs7:120206744-120206744;hs1:74853302-74853302,hs10:21655508-21655508;hs1:70902066-70902066,hs1:70901950-70901950;hs1:172900689-172900689,hs1:172884734-172884734;hs1:87206445-87206445,hs1:91156777-91156777;hs1:70902040-70902040,hs1:70901845-70901845;hs1:100636097-100636097,hs2:71819232-71819232;hs1:100636097-100636097,hs2:71819232-71819232;hs1:70902066-70902066,hs1:70901950-70901950;hs1:70902066-70902066,hs1:70901950-70901950;hs1:209898056-209898056,hs4:55298899-55298899;hs1:172095972-172095972,hs19:57924667-57924667;hs1:180004895-180004895,hs19:29290986-29290986;hs1:172095972-172095972,hs19:57924667-57924667;hs1:172556830-172556830,hs7:120206744-120206744;hs1:172556830-172556830,hs7:120206744-120206744;hs1:93367732-93367732,hs1:85296904-85296904;hs1:93367732-93367732,hs1:85296904-85296904;hs1:9101643-9101643,hs21:14455432-14455432;hs1:93378775-93378775,hs1:104119515-104119515;hs1:172084615-172084615,hs7:121631718-121631718;hs1:233362692-233362692,hs6:63681471-63681471;hs1:185276823-185276823,hs3:178605856-178605856;hs1:93533278-93533278,hs1:91156577-91156577;hs1:6353482-6353482,hs1:9357890-9357890;hs1:70902040-70902040,hs1:70901845-70901845;hs1:172084615-172084615,hs7:121631718-121631718;hs1:100636097-100636097,hs2:71819232-71819232;hs1:93529044-93529044,hs1:93378568-93378568;hs1:93529644-93529644,hs1:103919648-103919648;hs1:1388284-1388284,hs1:6005160-6005160;hs1:93378775-93378775,hs1:104119515-104119515;hs1:156390120-156390120,hs7:5580796-5580796;hs1:172556830-172556830,hs7:120206744-120206744;hs1:74858926-74858926,hs10:21655577-21655577;hs1:160885302-160885302,hs7:5549601-5549601;hs1:100636097-100636097,hs2:71819232-71819232;hs1:91156872-91156872,hs1:93529463-93529463;hs1:172084615-172084615,hs7:121631718-121631718;hs1:70913071-70913071,hs2:84098202-84098202;hs1:9101643-9101643,hs21:14455432-14455432;hs1:1388284-1388284,hs1:6005160-6005160;hs1:82321695-82321695,hs1:70902110-70902110;hs1:6000462-6000462,hs1:1350475-1350475;hs1:159918703-159918703,hs11:70816963-70816963;hs1:172556830-172556830,hs7:120206744-120206744;hs1:6353482-6353482,hs1:9357890-9357890;hs1:93529608-93529608,hs1:104031838-104031838;hs1:93378909-93378909,hs1:87237843-87237843;hs1:93367732-93367732,hs1:85296904-85296904;hs1:100636097-100636097,hs2:71819232-71819232;hs1:70902040-70902040,hs1:70901845-70901845;hs1:1388284-1388284,hs1:6005160-6005160;hs1:93528641-93528641,hs1:87237955-87237955;hs1:180004973-180004973,hs19:43663752-43663752;hs1:172084615-172084615,hs7:121631718-121631718;hs1:77830816-77830816,hs4:180923879-180923879;hs1:6353482-6353482,hs1:9357890-9357890;hs1:93528831-93528831,hs1:93529813-93529813;hs1:6353482-6353482,hs1:9357890-9357890;hs1:172556830-172556830,hs7:120206744-120206744;hs1:166857363-166857363,hs19:58528596-58528596;hs1:85302589-85302589,hs1:85302220-85302220;hs1:93367732-93367732,hs1:85296904-85296904;hs1:70902066-70902066,hs1:70901950-70901950;hs1:1388284-1388284,hs1:6005160-6005160;hs1:149210627-149210627,hs1:145038780-145038780;hs1:70902066-70902066,hs1:70901950-70901950;hs1:1388284-1388284,hs1:6005160-6005160;hs1:70902285-70902285,hs1:70930072-70930072;hs1:172084615-172084615,hs7:121631718-121631718;hs1:100636097-100636097,hs2:71819232-71819232;hs1:3047208-3047208,hs21:14423538-14423538;hs1:70902066-70902066,hs1:70901950-70901950;hs1:3047208-3047208,hs21:14423538-14423538;hs1:243075700-243075700,hs17:74803598-74803598;hs1:70912880-70912880,hs15:68500225-68500225;hs1:70902040-70902040,hs1:70901845-70901845;hs1:161253591-161253591,hs7:120165566-120165566;hs1:70902040-70902040,hs1:70901845-70901845;hs1:93378775-93378775,hs1:104119515-104119515;hs1:70902040-70902040,hs1:70901845-70901845;hs1:104032458-104032458,hs1:104290256-104290256;hs1:172095488-172095488,hs1:172094389-172094389;hs1:91143746-91143746,hs1:93529476-93529476;hs1:6353482-6353482,hs1:9357890-9357890;hs1:243067167-243067167,hs1:242924853-242924853;hs1:185280437-185280437,hs3:138845971-138845971;hs1:172084615-172084615,hs7:121631718-121631718;hs1:6353482-6353482,hs1:9357890-9357890;hs1:87277511-87277511,hs1:93379094-93379094;hs1:70902040-70902040,hs1:70901845-70901845;hs1:104032047-104032047,hs1:93529878-93529878;hs1:172884741-172884741,hs1:172133764-172133764;hs1:85296937-85296937,hs1:93528726-93528726;hs1:179585948-179585948,hs1:173388905-173388905;hs1:172556830-172556830,hs7:120206744-120206744;hs1:100636097-100636097,hs2:71819232-71819232;hs1:70902066-70902066,hs1:70901950-70901950;hs1:104031983-104031983,hs1:93395094-93395094;hs1:91143628-91143628,hs1:93395047-93395047;hs1:93395729-93395729,hs1:103222746-103222746;hs1:1388284-1388284,hs1:6005160-6005160;hs1:172095488-172095488,hs1:172094389-172094389;hs1:172556830-172556830,hs7:120206744-120206744;hs1:172556830-172556830,hs7:120206744-120206744;hs1:172556830-172556830,hs7:120206744-120206744;hs1:93378775-93378775,hs1:104119515-104119515;hs1:156330255-156330255,hs7:5001063-5001063;hs1:160198301-160198301,hs7:205796-205796;hs1:87206431-87206431,hs1:93378975-93378975;hs1:9101643-9101643,hs21:14455432-14455432;hs1:93367732-93367732,hs1:85296904-85296904;hs1:74853302-74853302,hs10:21655508-21655508;hs1:93378775-93378775,hs1:104119515-104119515;hs1:9101643-9101643,hs21:14455432-14455432;hs1:93378804-93378804,hs1:104031502-104031502;hs1:1388284-1388284,hs1:6005160-6005160;hs1:9101643-9101643,hs21:14455432-14455432;hs1:172095972-172095972,hs19:57924667-57924667;hs1:91143746-91143746,hs1:93379359-93379359;hs1:156282557-156282557,hs11:70441943-70441943;hs1:9101643-9101643,hs21:14455432-14455432;hs1:26990052-26990052,hs1:1387981-1387981;hs1:166027983-166027983,hs1:167282270-167282270;hs1:82321695-82321695,hs1:70902110-70902110;hs1:172556830-172556830,hs7:120206744-120206744;hs1:161253366-161253366,hs1:156333921-156333921;hs1:172556830-172556830,hs7:120206744-120206744;hs1:43742146-43742146,hs21:14455808-14455808;hs1:173523613-173523613,hs1:180005377-180005377;hs1:1388284-1388284,hs1:6005160-6005160;hs1:160198301-160198301,hs7:205796-205796;hs1:156282557-156282557,hs11:70441943-70441943;hs1:6353482-6353482,hs1:9357890-9357890;hs1:70902066-70902066,hs1:70901950-70901950;hs2:71819864-71819864,hs15:61841465-61841465;hs2:7044105-7044105,hs2:6197429-6197429;hs2:71819473-71819473,hs1:78698233-78698233;hs2:71819473-71819473,hs1:78698233-78698233;hs2:80891576-80891576,hs8:24107373-24107373;hs2:9139705-9139705,hs4:53365518-53365518;hs2:71819473-71819473,hs1:78698233-78698233;hs2:71819473-71819473,hs1:78698233-78698233;hs2:118506870-118506870,hs2:118506250-118506250;hs2:71819473-71819473,hs1:78698233-78698233;hs2:71459211-71459211,hs11:93059796-93059796;hs2:71819473-71819473,hs1:78698233-78698233;hs2:71819473-71819473,hs1:78698233-78698233;hs2:71819473-71819473,hs1:78698233-78698233;hs2:15063-15063,hs3:6970435-6970435;hs3:187538117-187538117,hs3:180978190-180978190;hs3:5846628-5846628,hs4:82888099-82888099;hs3:180936784-180936784,hs5:86786263-86786263;hs3:15021011-15021011,hs3:4693418-4693418;hs3:2329124-2329124,hs7:63480111-63480111;hs3:170795474-170795474,hs3:178778908-178778908;hs3:15021011-15021011,hs3:4693418-4693418;hs3:4694739-4694739,hs3:4694944-4694944;hs3:170795474-170795474,hs3:178778908-178778908;hs3:165213959-165213959,hs19:37316084-37316084;hs3:170795105-170795105,hs3:170784203-170784203;hs3:138852436-138852436,hs15:98358782-98358782;hs3:12019894-12019894,hs4:98112195-98112195;hs3:82416344-82416344,hs17:46795293-46795293;hs3:170795105-170795105,hs3:170784203-170784203;hs3:5974164-5974164,hs9:22508578-22508578;hs3:82575039-82575039,hs3:82495992-82495992;hs3:12006971-12006971,hs10:23756574-23756574;hs3:192473223-192473223,hs12:71316940-71316940;hs3:180624536-180624536,hs5:74980985-74980985;hs3:4695258-4695258,hs3:4694993-4694993;hs3:167259277-167259277,hs4:98086468-98086468;hs3:195273073-195273073,hs5:76377101-76377101;hs3:15287825-15287825,hs9:8844123-8844123;hs3:170795105-170795105,hs3:170784203-170784203;hs3:12024843-12024843,hs3:11999859-11999859;hs3:15292242-15292242,hs9:20618911-20618911;hs3:165213959-165213959,hs19:37316084-37316084;hs3:4687165-4687165,hs10:23690637-23690637;hs3:15290795-15290795,hs9:8529973-8529973;hs3:4694739-4694739,hs3:4694944-4694944;hs3:4694739-4694739,hs3:4694944-4694944;hs3:72569665-72569665,hs10:30172362-30172362;hs3:15290795-15290795,hs9:8529973-8529973;hs3:178596176-178596176,hs1:185276850-185276850;hs3:170795474-170795474,hs3:178778908-178778908;hs3:15021011-15021011,hs3:4693418-4693418;hs3:101399649-101399649,hs3:101383422-101383422;hs3:15021011-15021011,hs3:4693418-4693418;hs3:5846628-5846628,hs4:85459106-85459106;hs3:82624889-82624889,hs17:46483701-46483701;hs3:180623991-180623991,hs3:177881229-177881229;hs3:82416941-82416941,hs17:46795973-46795973;hs3:541478-541478,hs17:46782942-46782942;hs3:184087367-184087367,hs16:71330183-71330183;hs3:195285231-195285231,hs5:79358296-79358296;hs3:72550105-72550105,hs10:30139837-30139837;hs3:15021011-15021011,hs3:4693418-4693418;hs3:178793882-178793882,hs3:170803583-170803583;hs3:195109488-195109488,hs16:69688839-69688839;hs3:182267718-182267718,hs16:71533437-71533437;hs3:15287825-15287825,hs9:8844123-8844123;hs3:15287825-15287825,hs9:8844123-8844123;hs3:180997984-180997984,hs16:70358333-70358333;hs3:184204999-184204999,hs11:76421381-76421381;hs3:11150397-11150397,hs3:11152579-11152579;hs3:178854408-178854408,hs16:69024690-69024690;hs3:4695258-4695258,hs3:4694993-4694993;hs3:4686610-4686610,hs10:23757532-23757532;hs3:15290041-15290041,hs3:15203222-15203222;hs3:12024095-12024095,hs3:12008812-12008812;hs3:170795521-170795521,hs3:178810942-178810942;hs3:5845439-5845439,hs17:57929877-57929877;hs3:7465693-7465693,hs2:7043690-7043690;hs3:15021011-15021011,hs3:4693418-4693418;hs3:160652390-160652390,hs3:160689213-160689213;hs3:195109488-195109488,hs16:69688839-69688839;hs3:16292010-16292010,hs3:16308081-16308081;hs3:35797097-35797097,hs3:102654096-102654096;hs3:161004253-161004253,hs3:138837856-138837856;hs3:4694739-4694739,hs3:4694944-4694944;hs3:75733620-75733620,hs14:23976011-23976011;hs3:12049779-12049779,hs4:98106323-98106323;hs3:82483305-82483305,hs17:46749312-46749312;hs3:166625333-166625333,hs7:68005688-68005688;hs3:166617650-166617650,hs4:58563869-58563869;hs3:179288353-179288353,hs5:65384385-65384385;hs3:86749114-86749114,hs3:86823887-86823887;hs3:15197163-15197163,hs10:23757744-23757744;hs3:15107553-15107553,hs3:15127210-15127210;hs3:182060486-182060486,hs3:182260642-182260642;hs3:180997984-180997984,hs16:70358333-70358333;hs3:182229958-182229958,hs5:79265806-79265806;hs3:15287825-15287825,hs9:8844123-8844123;hs3:180624603-180624603,hs3:183910436-183910436;hs3:4695258-4695258,hs3:4694993-4694993;hs3:4695258-4695258,hs3:4694993-4694993;hs3:8678234-8678234,hs2:289231-289231;hs3:15292242-15292242,hs9:20618911-20618911;hs3:166651883-166651883,hs10:20080863-20080863;hs3:8587349-8587349,hs13:91486570-91486570;hs4:189725793-189725793,hs3:194982906-194982906;hs4:212726-212726,hs15:96050109-96050109;hs4:99679247-99679247,hs1:74794908-74794908;hs4:54743107-54743107,hs3:15127418-15127418;hs4:76744847-76744847,hs9:65640088-65640088;hs4:53917536-53917536,hs3:85554829-85554829;hs4:98896509-98896509,hs10:35324314-35324314;hs4:98899421-98899421,hs4:98797873-98797873;hs4:98896509-98896509,hs10:35324248-35324248;hs4:98899421-98899421,hs4:98797873-98797873;hs4:70920485-70920485,hs4:1367076-1367076;hs4:54710677-54710677,hs4:54711866-54711866;hs4:98146087-98146087,hs3:11980209-11980209;hs4:98899421-98899421,hs4:98797873-98797873;hs4:98877586-98877586,hs4:98896783-98896783;hs4:99029367-99029367,hs3:16298808-16298808;hs4:98896509-98896509,hs10:35324248-35324248;hs4:98896509-98896509,hs10:35324248-35324248;hs4:98896509-98896509,hs10:35324314-35324314;hs4:1365789-1365789,hs4:177690981-177690981;hs4:98896509-98896509,hs10:35324248-35324248;hs4:99029367-99029367,hs3:16298808-16298808;hs4:98896509-98896509,hs10:35324248-35324248;hs4:98896509-98896509,hs10:35324314-35324314;hs4:98877586-98877586,hs4:98896783-98896783;hs4:99029367-99029367,hs3:16298808-16298808;hs4:99656378-99656378,hs1:208320772-208320772;hs4:85608249-85608249,hs17:46671496-46671496;hs4:54709981-54709981,hs4:54709848-54709848;hs4:98899421-98899421,hs4:98797873-98797873;hs4:98896509-98896509,hs10:35324248-35324248;hs4:85608249-85608249,hs17:46671496-46671496;hs4:98877586-98877586,hs4:98896783-98896783;hs4:98194984-98194984,hs3:86737862-86737862;hs4:25646685-25646685,hs4:22833333-22833333;hs4:99029367-99029367,hs3:16298808-16298808;hs4:99029367-99029367,hs3:16298808-16298808;hs4:99029367-99029367,hs3:16298808-16298808;hs4:98896509-98896509,hs10:35324248-35324248;hs4:98896509-98896509,hs10:35324248-35324248;hs4:98156931-98156931,hs3:12029257-12029257;hs4:98896509-98896509,hs10:35324314-35324314;hs4:98877586-98877586,hs4:98896783-98896783;hs4:98899421-98899421,hs4:98797873-98797873;hs4:98896509-98896509,hs10:35324314-35324314;hs4:85757836-85757836,hs4:85758626-85758626;hs4:98899421-98899421,hs4:98797873-98797873;hs4:52966718-52966718,hs3:543272-543272;hs4:98899421-98899421,hs4:98797873-98797873;hs4:98896509-98896509,hs10:35324248-35324248;hs4:98896509-98896509,hs10:35324314-35324314;hs4:99029367-99029367,hs3:16298808-16298808;hs4:99029367-99029367,hs3:16298808-16298808;hs4:98877586-98877586,hs4:98896783-98896783;hs4:98899421-98899421,hs4:98797873-98797873;hs4:86333503-86333503,hs4:85958205-85958205;hs4:22027529-22027529,hs4:25645834-25645834;hs4:24462465-24462465,hs4:24577615-24577615;hs4:99029367-99029367,hs3:16298808-16298808;hs4:99029367-99029367,hs3:16298808-16298808;hs4:98899421-98899421,hs4:98797873-98797873;hs4:98877586-98877586,hs4:98896783-98896783;hs4:98896509-98896509,hs10:35324314-35324314;hs4:98896509-98896509,hs10:35324314-35324314;hs4:99029367-99029367,hs3:16298808-16298808;hs4:99751185-99751185,hs10:21677262-21677262;hs4:98877586-98877586,hs4:98896783-98896783;hs4:98896509-98896509,hs10:35324314-35324314;hs4:25120540-25120540,hsX:32076076-32076076;hs4:22032610-22032610,hs4:22027006-22027006;hs4:76741108-76741108,hs4:177693690-177693690;hs4:99029367-99029367,hs3:16298808-16298808;hs4:98896509-98896509,hs10:35324248-35324248;hs4:98896750-98896750,hs19:11481926-11481926;hs4:101856148-101856148,hs4:101858366-101858366;hs4:54711581-54711581,hs4:54709934-54709934;hs4:98896509-98896509,hs10:35324248-35324248;hs4:70920485-70920485,hs4:1367076-1367076;hs4:54710767-54710767,hsX:43675147-43675147;hs4:99029367-99029367,hs3:16298808-16298808;hs4:98899421-98899421,hs4:98797873-98797873;hs4:98896509-98896509,hs10:35324314-35324314;hs4:54365729-54365729,hs10:23757530-23757530;hs5:50321834-50321834,hs3:192472894-192472894;hs5:72317596-72317596,hs16:69016559-69016559;hs5:65397743-65397743,hs3:192624882-192624882;hs5:86763366-86763366,hs5:51088889-51088889;hs5:92854789-92854789,hs13:22369067-22369067;hs5:75520193-75520193,hs12:71803837-71803837;hs5:72209751-72209751,hs3:182256349-182256349;hs5:74444809-74444809,hs12:118956958-118956958;hs5:72317596-72317596,hs16:69016559-69016559;hs5:162855469-162855469,hsX:2132962-2132962;hs5:92853886-92853886,hs12:126199763-126199763;hs5:91725437-91725437,hs5:60191758-60191758;hs5:65579636-65579636,hs3:180623779-180623779;hs5:72317596-72317596,hs16:69016559-69016559;hs5:72317596-72317596,hs16:69016559-69016559;hs5:71341424-71341424,hs3:190514111-190514111;hs6:105437995-105437995,hs6:169287422-169287422;hs6:168916395-168916395,hs15:95016379-95016379;hs6:170911804-170911804,hs9:66486154-66486154;hs7:5001402-5001402,hs7:120195946-120195946;hs7:2638807-2638807,hs1:160823041-160823041;hs7:21099388-21099388,hs12:69103938-69103938;hs7:199487-199487,hs1:167302555-167302555;hs7:199487-199487,hs1:167302555-167302555;hs7:131921351-131921351,hs3:12053355-12053355;hs7:120205941-120205941,hs7:872069-872069;hs7:121686996-121686996,hs11:71646609-71646609;hs7:1612638-1612638,hs1:165858684-165858684;hs7:1612638-1612638,hs1:165858684-165858684;hs7:120205941-120205941,hs7:872069-872069;hs7:121686996-121686996,hs11:71646609-71646609;hs7:22410978-22410978,hs12:69048634-69048634;hs7:131921351-131921351,hs3:12053355-12053355;hs7:22422759-22422759,hs12:69110477-69110477;hs7:20561055-20561055,hs5:74443544-74443544;hs7:121686996-121686996,hs11:71646609-71646609;hs7:121686996-121686996,hs11:71646609-71646609;hs7:19453389-19453389,hs12:68759525-68759525;hs7:19473283-19473283,hs7:21140333-21140333;hs7:158908504-158908504,hs1:149029499-149029499;hs7:66569382-66569382,hs2:14386-14386;hs7:121686996-121686996,hs11:71646609-71646609;hs7:121686996-121686996,hs11:71646609-71646609;hs7:121686996-121686996,hs11:71646609-71646609;hs7:121686996-121686996,hs11:71646609-71646609;hs7:121686996-121686996,hs11:71646609-71646609;hs7:121686996-121686996,hs11:71646609-71646609;hs7:155927722-155927722,hs7:155710758-155710758;hs7:120205941-120205941,hs7:872069-872069;hs7:121865548-121865548,hs4:54487442-54487442;hs7:121686996-121686996,hs11:71646609-71646609;hs7:2638807-2638807,hs1:160823041-160823041;hs7:121686996-121686996,hs11:71646609-71646609;hs7:120195538-120195538,hs7:119534814-119534814;hs7:131921351-131921351,hs3:12053355-12053355;hs8:37740288-37740288,hs17:22045781-22045781;hs8:98692712-98692712,hs18:65833348-65833348;hs8:82627827-82627827,hs18:65931623-65931623;hs8:137523518-137523518,hs8:136815040-136815040;hs8:145745120-145745120,hs9:82663705-82663705;hs8:29278130-29278130,hs8:31524744-31524744;hs8:79555309-79555309,hs16:34173267-34173267;hs8:77015064-77015064,hs8:77021508-77021508;hs8:82627551-82627551,hs15:24179324-24179324;hs8:146300725-146300725,hs15:74135478-74135478;hs8:139643412-139643412,hs8:136822660-136822660;hs9:9462153-9462153,hs3:141049257-141049257;hs9:33636714-33636714,hs9:35923316-35923316;hs9:20128963-20128963,hs9:20128714-20128714;hs9:11308978-11308978,hs9:38064823-38064823;hs9:11302836-11302836,hs9:11322076-11322076;hs9:9462153-9462153,hs3:141049257-141049257;hs9:33790488-33790488,hs13:91202708-91202708;hs9:33403576-33403576,hs9:20145650-20145650;hs9:36191167-36191167,hs9:29533137-29533137;hs9:36519783-36519783,hs14:27594854-27594854;hs9:9462153-9462153,hs3:141049257-141049257;hs9:8530256-8530256,hs3:14999955-14999955;hs9:33636896-33636896,hs9:35923578-35923578;hs9:20766393-20766393,hs9:36159530-36159530;hs9:36163032-36163032,hs9:10129911-10129911;hs9:9462153-9462153,hs9:9462194-9462194;hs9:26635925-26635925,hs9:36188553-36188553;hs9:20939191-20939191,hs15:92520463-92520463;hs9:11929646-11929646,hs9:21069639-21069639;hs9:119301060-119301060,hs4:26878875-26878875;hs9:20939191-20939191,hs15:92520463-92520463;hs9:20129126-20129126,hs3:79481664-79481664;hs9:26749881-26749881,hs9:35923198-35923198;hs9:23019619-23019619,hs9:11931528-11931528;hs9:22567290-22567290,hs3:12006065-12006065;hs9:8530256-8530256,hs3:14999955-14999955;hs9:9462153-9462153,hs9:9462194-9462194;hs9:119301060-119301060,hs4:26878875-26878875;hs9:1125315-1125315,hs3:81808839-81808839;hs9:10757096-10757096,hs13:44461320-44461320;hs9:20766393-20766393,hs9:36159530-36159530;hs9:20766393-20766393,hs9:36159530-36159530;hs9:8530120-8530120,hs10:23697017-23697017;hs9:11338916-11338916,hs9:29535141-29535141;hs9:103953410-103953410,hs9:103906337-103906337;hs9:119301060-119301060,hs4:26878875-26878875;hs10:30175012-30175012,hs3:78507937-78507937;hs10:72835023-72835023,hs10:72827068-72827068;hs10:27422333-27422333,hs10:27425028-27425028;hs10:30140930-30140930,hs10:30179984-30179984;hs10:25002502-25002502,hs9:116648705-116648705;hs10:35324517-35324517,hs4:98874174-98874174;hs10:35324517-35324517,hs4:98874174-98874174;hs10:23754611-23754611,hs3:4686444-4686444;hs10:23691171-23691171,hs10:23757314-23757314;hs10:35324517-35324517,hs4:98874174-98874174;hs10:3792115-3792115,hsX:2063687-2063687;hs10:42404439-42404439,hs4:98198062-98198062;hs10:23700233-23700233,hs3:102654512-102654512;hs10:29265724-29265724,hs10:27421003-27421003;hs10:30126645-30126645,hs3:72549307-72549307;hs10:30173349-30173349,hs10:30138632-30138632;hs10:595783-595783,hs17:67173031-67173031;hs10:24030492-24030492,hs3:4687482-4687482;hs10:109275068-109275068,hs10:109271006-109271006;hs10:21730882-21730882,hs10:21600697-21600697;hs10:36972949-36972949,hs4:58503826-58503826;hs10:29958978-29958978,hs17:61596056-61596056;hs10:30174700-30174700,hs10:30138603-30138603;hs10:30173903-30173903,hs10:30174604-30174604;hs10:30179755-30179755,hs10:30172825-30172825;hs10:595783-595783,hs17:67173031-67173031;hs10:35324517-35324517,hs4:98874174-98874174;hs10:30174848-30174848,hs10:30174657-30174657;hs10:23992667-23992667,hs3:15221354-15221354;hs10:21678052-21678052,hs9:19875641-19875641;hs10:35324517-35324517,hs4:98874174-98874174;hs10:23754496-23754496,hs3:4686932-4686932;hs10:35324517-35324517,hs4:98874174-98874174;hs10:27421003-27421003,hs10:29265628-29265628;hs10:18231777-18231777,hs10:22215434-22215434;hs10:24030492-24030492,hs3:4687482-4687482;hs10:35324517-35324517,hs4:98874174-98874174;hs10:28415283-28415283,hs10:28415825-28415825;hs10:23755320-23755320,hs3:12006971-12006971;hs10:35324517-35324517,hs4:98874174-98874174;hs10:35324517-35324517,hs4:98874174-98874174;hs11:70811989-70811989,hs7:120197629-120197629;hs11:70811989-70811989,hs7:120197629-120197629;hs11:70817294-70817294,hs7:5021666-5021666;hs11:70811989-70811989,hs7:120197629-120197629;hs11:133286072-133286072,hs4:43484836-43484836;hs11:70811989-70811989,hs7:120197629-120197629;hs11:70817294-70817294,hs7:5021666-5021666;hs11:70811989-70811989,hs7:120197629-120197629;hs11:95975261-95975261,hs1:100636385-100636385;hs11:70811989-70811989,hs7:120197629-120197629;hs11:70817294-70817294,hs7:5021666-5021666;hs11:95975261-95975261,hs1:100636385-100636385;hs11:95975261-95975261,hs1:100636385-100636385;hs11:70811989-70811989,hs7:120197629-120197629;hs11:70811989-70811989,hs7:120197629-120197629;hs11:70817294-70817294,hs7:5021666-5021666;hs11:70811989-70811989,hs7:120197629-120197629;hs11:70811989-70811989,hs7:120197629-120197629;hs11:70811989-70811989,hs7:120197629-120197629;hs11:95975261-95975261,hs1:100636385-100636385;hs11:129717827-129717827,hs11:120675489-120675489;hs11:95975261-95975261,hs1:100636385-100636385;hs11:70811989-70811989,hs7:120197629-120197629;hs11:95975261-95975261,hs1:100636385-100636385;hs11:129717827-129717827,hs11:120675489-120675489;hs11:70817294-70817294,hs7:5021666-5021666;hs11:70817294-70817294,hs7:5021666-5021666;hs11:70811989-70811989,hs7:120197629-120197629;hs11:70811989-70811989,hs7:120197629-120197629;hs11:70811989-70811989,hs7:120197629-120197629;hs11:124655876-124655876,hs1:99353049-99353049;hs11:129717827-129717827,hs11:120675489-120675489;hs11:70811989-70811989,hs7:120197629-120197629;hs12:70751774-70751774,hs6:168689327-168689327;hs12:29169047-29169047,hs3:138845434-138845434;hs12:33972671-33972671,hs12:33974591-33974591;hs12:118957160-118957160,hs12:118957224-118957224;hs12:70740405-70740405,hs9:36519915-36519915;hs12:71816743-71816743,hs13:19561647-19561647;hs12:128644644-128644644,hs12:29742801-29742801;hs12:68877086-68877086,hs7:22426435-22426435;hs12:69049477-69049477,hs7:22449204-22449204;hs12:53871783-53871783,hs12:48667856-48667856;hs12:10914284-10914284,hs8:122566200-122566200;hs12:33938595-33938595,hs12:33972945-33972945;hs12:69105672-69105672,hs7:19235563-19235563;hs12:40767333-40767333,hsX:58202890-58202890;hs12:131996561-131996561,hs3:30802738-30802738;hs12:34245535-34245535,hsX:56839578-56839578;hs12:128493889-128493889,hs3:30863319-30863319;hs13:93593031-93593031,hs13:92527272-92527272;hs13:44115152-44115152,hs9:36142205-36142205;hs13:81595278-81595278,hs13:95084299-95084299;hs13:93489176-93489176,hs13:92805016-92805016;hs13:20098150-20098150,hs13:23977582-23977582;hs13:44455500-44455500,hs9:10076887-10076887;hs13:44389922-44389922,hs13:41603387-41603387;hs13:48324959-48324959,hs13:45929181-45929181;hs13:44115152-44115152,hs9:36142205-36142205;hs13:81583821-81583821,hs13:93589811-93589811;hs13:40407883-40407883,hs13:48949460-48949460;hs13:22290856-22290856,hs5:92896066-92896066;hs13:92527564-92527564,hs9:36404708-36404708;hs13:20098150-20098150,hs13:23977582-23977582;hs13:44455500-44455500,hs9:10076887-10076887;hs13:44115152-44115152,hs9:36142205-36142205;hs13:24169897-24169897,hs13:22366030-22366030;hs13:28558489-28558489,hs4:43132784-43132784;hs13:45909564-45909564,hs9:33313824-33313824;hs14:96868333-96868333,hs1:242937017-242937017;hs14:24022623-24022623,hs14:94667939-94667939;hs14:24930559-24930559,hs4:128974-128974;hs15:66769418-66769418,hs2:71459254-71459254;hs15:62478682-62478682,hs2:8221107-8221107;hs15:95378103-95378103,hs7:17274763-17274763;hs15:98358768-98358768,hs3:160991095-160991095;hs15:68500732-68500732,hs1:70902258-70902258;hs15:49544853-49544853,hsY:19335468-19335468;hs15:95175959-95175959,hs9:21631128-21631128;hs15:49130288-49130288,hsY:23576843-23576843;hs15:93273055-93273055,hs15:94346057-94346057;hs15:31949975-31949975,hs15:90625576-90625576;hs15:68500732-68500732,hs1:70902258-70902258;hs15:68500517-68500517,hs1:70912909-70912909;hs15:95377822-95377822,hs15:94344953-94344953;hs16:88850021-88850021,hs16:87514544-87514544;hs16:34190007-34190007,hs8:76948540-76948540;hs16:71562128-71562128,hs5:72366554-72366554;hs16:71562128-71562128,hs5:72366554-72366554;hs16:71095951-71095951,hs3:184638012-184638012;hs16:70358774-70358774,hs3:195458447-195458447;hs16:88850021-88850021,hs16:87514544-87514544;hs16:34173784-34173784,hs8:77015088-77015088;hs16:70358774-70358774,hs3:195458447-195458447;hs16:70358774-70358774,hs3:195458447-195458447;hs16:71562128-71562128,hs5:72366554-72366554;hs17:74452610-74452610,hs1:243110384-243110384;hs17:46766435-46766435,hs3:36002586-36002586;hs17:58357672-58357672,hs10:29959263-29959263;hs17:46750521-46750521,hs3:82503372-82503372;hs17:46795973-46795973,hs3:82416898-82416898;hs17:51301022-51301022,hs9:31073517-31073517;hs17:28730205-28730205,hs3:116564344-116564344;hs17:57941464-57941464,hs3:5489734-5489734;hs17:74545896-74545896,hs1:243075110-243075110;hs17:58357672-58357672,hs10:29959263-29959263;hs17:58357672-58357672,hs10:29959263-29959263;hs18:65833537-65833537,hs18:65854095-65854095;hs18:368580-368580,hs17:49485454-49485454;hs19:29058558-29058558,hs19:42172199-42172199;hs19:101618-101618,hs21:23170923-23170923;hs19:42308296-42308296,hs19:31630638-31630638;hs19:58582606-58582606,hs19:58528582-58528582;hs19:57925787-57925787,hs1:172148357-172148357;hs19:57925787-57925787,hs1:172148357-172148357;hs19:57925787-57925787,hs1:172148357-172148357;hs19:11481921-11481921,hs4:98896298-98896298;hs19:101083-101083,hs21:23171364-23171364;hs20:29648057-29648057,hs14:20456397-20456397;hs21:14439767-14439767,hs1:58002304-58002304;hs21:14441193-14441193,hs1:70820633-70820633;hs21:14441193-14441193,hs1:70820633-70820633;hs21:14589522-14589522,hs21:14590325-14590325;hs21:14439767-14439767,hs1:58002304-58002304;hs21:14441193-14441193,hs1:70820633-70820633;hs21:14441193-14441193,hs1:70820633-70820633;hs21:14441193-14441193,hs1:70820633-70820633;hs21:14439767-14439767,hs1:58002304-58002304;hs22:31013881-31013881,hs3:166652456-166652456;hsX:135769017-135769017,hsX:135694163-135694163;hsX:42181867-42181867,hs4:85059414-85059414;hsX:53372262-53372262,hs4:24976979-24976979;hsX:133113989-133113989,hsX:129433359-129433359;hsX:120421290-120421290,hsX:137336303-137336303;hsX:31964427-31964427,hs4:98148746-98148746;hsX:32066092-32066092,hs7:131921179-131921179;hsX:62662984-62662984,hs12:40763910-40763910;hsX:32066092-32066092,hs7:131921179-131921179;hsX:53723984-53723984,hsX:53370517-53370517;hsX:31873296-31873296,hs3:12022402-12022402;hsX:31842951-31842951,hs3:166601227-166601227;hsX:57136705-57136705,hsX:57906222-57906222;hsX:32066092-32066092,hs7:131921179-131921179;hsX:57644938-57644938,hsX:67067367-67067367;hsX:135767758-135767758,hsX:126112488-126112488 Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 C4orf37,CUL2;C4orf37,OXNAD1;CUL2,C4orf37;CUL2,OXNAD1;DPH3,C4orf37;KIAA1530,CSN1S2AP;KIAA1530,VEGFC CTDB0390 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 19 Glioma Next Generation Sequencing Homo sapiens SJHGG017_D Illumina Genome Analyzer IIx or HiSeq chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-51025700:0;chr17:51025701-81160200:1;chr17:81160201-81195210:0;chr18:0-78077248:0;chr19:0-42798400:0;chr19:42798401-42890591:-1;chr19:42890592-45876123:0;chr19:45876124-45876822:-1;chr19:45876823-45876822:0;chr19:45876823-47930700:-1;chr19:47930701-47930700:0;chr19:47930701-55103700:-1;chr19:55103701-55103700:0;chr19:55103701-55669739:-1;chr19:55669740-55669739:0;chr19:55669740-59118800:-1;chr19:59118801-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-155288619:0;chr2:155288620-155288700:1;chr2:155288701-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-53103600:0;chr8:146303801-146364022:0;chr8:53103601-146303800:1;chr9:0-10000:0;chr9:10001-140772668:1;chr9:140772669-140773505:0;chr9:140773506-141102500:1;chr9:141102501-141213431:0;chrX:0-155270560:0;chrY:0-2649500:0;chrY:2649501-28817600:-1;chrY:28817601-59373566:0 hs19:40936318-40936318,hs19:40490842-40490842;hs19:55668538-55668538,hs19:47930726-47930726;hs19:55664092-55664092,hs10:121613523-121613523;hs10:130144300-130144300,hs19:46258672-46258672;hs19:55664092-55664092,hs10:121613523-121613523;hs19:38422818-38422818,hs19:55669249-55669249;hs19:37197984-37197984,hs19:37095913-37095913;hs19:37219530-37219530,hs19:37003614-37003614;hs19:46432959-46432959,hs19:45846358-45846358 C19orf51;C5AR1;C8orf33;C9orf66;CD3EAP;CHMP2A;CIC;DHX34;EPS8L1;ERCC1;FOSB;GLTSCR1;GPR77;KLC3;KPTN;LILRA1;LOC388553;MEGF8;MEIS3;MZF1;NAPA;PAFAH1B3;PPP1R12C;PPP1R13L;PPP6R1;PRR19;PRR24;PTPRH;RTN2;SIPA1L3;SLC8A2;SYT5;TMEM145;TMEM86B;TNNI3;TNNT1;TRIM28;UBE2M;ZBTB45;ZNF529;ZNF541;ZNF567; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes ZNF529,ZNF567 CTDB0391 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 7 Glioma Next Generation Sequencing Homo sapiens SJHGG019_E Illumina Genome Analyzer IIx or HiSeq chr10:0-29724120:0;chr10:29724121-29725468:-1;chr10:29725469-135534747:0;chr11:0-54951600:0;chr11:134946401-135006516:0;chr11:54951601-57527368:-1;chr11:57527369-82843400:0;chr11:82843401-134946400:-1;chr12:0-146200:0;chr12:132129601-132130400:0;chr12:132130401-133841500:1;chr12:133841501-133851895:0;chr12:146201-132129600:1;chr13:0-19125100:0;chr13:19125101-20016700:-1;chr13:20016701-115169878:0;chr14:0-19964300:0;chr14:107289501-107349540:0;chr14:19964301-22313700:-1;chr14:22313701-22981000:0;chr14:22981001-69670528:-1;chr14:69670529-69678041:0;chr14:69678042-107289500:-1;chr15:0-25313000:0;chr15:102521201-102531392:0;chr15:25313001-76622300:1;chr15:76622301-76640100:0;chr15:76640101-102521200:1;chr16:0-491380:0;chr16:32579628-32602840:-1;chr16:32602841-57021623:0;chr16:491381-5306900:1;chr16:5306901-32579627:0;chr16:57021624-70844000:-1;chr16:70844001-70862600:0;chr16:70862601-71202500:-1;chr16:71202501-71202500:0;chr16:71202501-90292700:-1;chr16:90292701-90354753:0;chr17:0-0:0;chr17:1-9152635:-1;chr17:10472147-10472146:0;chr17:10472147-12553016:1;chr17:12553017-12553016:0;chr17:12553017-12556411:1;chr17:12556412-12556411:0;chr17:12556412-21547300:1;chr17:21547301-21685300:0;chr17:21685301-22244500:1;chr17:22244501-47563225:0;chr17:47563226-54457337:-1;chr17:54457338-54475403:0;chr17:54475404-81195100:1;chr17:81195101-81195210:0;chr17:9152636-9152635:0;chr17:9152636-9156674:1;chr17:9156675-10472146:1;chr17:9156675-9156674:0;chr18:0-10000:0;chr18:10001-611800:1;chr18:10175701-10175900:0;chr18:10175901-10572600:1;chr18:10572601-10578600:0;chr18:10578601-10667800:1;chr18:10667801-10667800:0;chr18:10667801-15133800:1;chr18:1076501-1076500:0;chr18:1076501-1095200:1;chr18:1095201-1095200:0;chr18:1095201-1106353:1;chr18:1106354-1106353:0;chr18:1106354-9968351:1;chr18:15133801-78077248:0;chr18:611801-611800:0;chr18:611801-835400:1;chr18:835401-835600:0;chr18:835601-903595:1;chr18:903596-1076500:1;chr18:903596-903595:0;chr18:9968352-10175700:1;chr18:9968352-9968351:0;chr19:0-51211400:0;chr19:51211401-59118800:-1;chr19:59118801-59128983:0;chr1:0-819600:0;chr1:15548770-15548769:0;chr1:15548770-16786988:1;chr1:16786989-16786988:0;chr1:16786989-34461945:1;chr1:193727004-193860372:0;chr1:193860373-194088940:1;chr1:194088941-194088940:0;chr1:194088941-194169600:1;chr1:194169601-194171400:0;chr1:194171401-195495654:1;chr1:195495655-195552586:0;chr1:195552587-195552837:1;chr1:195552838-195552864:0;chr1:195552865-249240500:1;chr1:249240501-249250621:0;chr1:34461946-34461945:0;chr1:34461946-55959700:1;chr1:55959701-55963200:0;chr1:55963201-193727003:1;chr1:819601-15548769:1;chr20:0-24961256:0;chr20:24961257-26319500:-1;chr20:26319501-42178022:0;chr20:42178023-42312177:-1;chr20:42312178-43648400:0;chr20:43648401-43683190:-1;chr20:43683191-43683190:0;chr20:43683191-43685448:1;chr20:43685449-43685448:0;chr20:43685449-43734200:-1;chr20:43734201-43734977:0;chr20:43734978-44779160:-1;chr20:44779161-44779160:0;chr20:44779161-44779459:1;chr20:44779460-44821200:0;chr20:44821201-45052769:-1;chr20:45052770-55921500:0;chr20:55921501-56241001:-1;chr20:56241002-56241290:0;chr20:56241291-56416900:-1;chr20:56416901-56426355:0;chr20:56426356-56426519:1;chr20:56426520-56427143:0;chr20:56427144-56427397:1;chr20:56427398-56427397:0;chr20:56427398-62965000:-1;chr20:62965001-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-10000:0;chr2:10001-3964064:1;chr2:14341477-14342747:0;chr2:14342748-89890400:1;chr2:176927801-177065200:0;chr2:177065201-243183600:1;chr2:243183601-243199373:0;chr2:3964065-3965113:0;chr2:3965114-5661024:1;chr2:5661025-5661216:0;chr2:5661217-6209834:1;chr2:6209835-6209834:0;chr2:6209835-6210152:1;chr2:6210153-14341476:1;chr2:6210153-6210152:0;chr2:89890401-95328000:0;chr2:95328001-176927800:1;chr3:0-60200:0;chr3:60201-90504800:-1;chr3:90504801-198022430:0;chr4:0-10500:0;chr4:10501-6625400:-1;chr4:111277369-117199152:-1;chr4:117199153-134597500:0;chr4:134597501-139135082:-1;chr4:139135083-139135772:0;chr4:139135773-139135939:-1;chr4:139135940-151010360:0;chr4:151010361-191043900:-1;chr4:191043901-191154276:0;chr4:28785401-41628800:0;chr4:41628801-48836200:-1;chr4:48836201-111277368:0;chr4:6625401-28785400:-1;chr4:6625401-6625400:0;chr5:0-39732051:0;chr5:156635001-156635583:1;chr5:156635584-158483014:0;chr5:158483015-180736100:1;chr5:180736101-180915260:0;chr5:39732052-40087311:1;chr5:40087312-156635000:0;chr6:0-171115067:0;chr7:0-10000:0;chr7:10001-6705600:1;chr7:142329001-142329000:0;chr7:142329001-142494000:1;chr7:142494001-142494000:0;chr7:142494001-159128500:1;chr7:159128501-159138663:0;chr7:20822801-20838700:0;chr7:20838701-54773922:1;chr7:54773923-54773922:0;chr7:54773923-54779600:1;chr7:54779601-54779600:0;chr7:54779601-54782520:1;chr7:54782521-54782520:0;chr7:54782521-54784298:1;chr7:54784299-54784298:0;chr7:54784299-54784400:1;chr7:54784401-54784400:0;chr7:54784401-54785900:1;chr7:54785901-54785900:0;chr7:54785901-54786000:1;chr7:54786001-54786000:0;chr7:54786001-54789800:1;chr7:54789801-54789800:0;chr7:54789801-54790449:1;chr7:54790450-54790449:0;chr7:54790450-54799600:1;chr7:54799601-54799600:0;chr7:54799601-54879471:1;chr7:54879472-54879471:0;chr7:54879472-54880958:1;chr7:54880959-54880958:0;chr7:54880959-54881840:1;chr7:54881841-54881840:0;chr7:54881841-54894665:1;chr7:54894666-54894665:0;chr7:54894666-54895600:1;chr7:54895601-54895600:0;chr7:54895601-54902699:1;chr7:54902700-54902699:0;chr7:54902700-54906701:1;chr7:54906702-54906701:0;chr7:54906702-54907100:1;chr7:54907101-54907100:0;chr7:54907101-54908000:1;chr7:54908001-54908000:0;chr7:54908001-54908078:1;chr7:54908079-54908078:0;chr7:54908079-54916540:1;chr7:54916541-54916540:0;chr7:54916541-54916600:1;chr7:54916601-54916600:0;chr7:54916601-54952744:1;chr7:54952745-54952744:0;chr7:54952745-54959954:1;chr7:54959955-54959954:0;chr7:54959955-54963734:1;chr7:54963735-54963734:0;chr7:54963735-54963959:1;chr7:54963960-54963959:0;chr7:54963960-54980294:1;chr7:54980295-54980294:0;chr7:54980295-55052400:1;chr7:55052401-55052400:0;chr7:55052401-55053900:1;chr7:55053901-55053900:0;chr7:55053901-55058700:1;chr7:55058701-55058700:0;chr7:55058701-55081919:1;chr7:55081920-55081919:0;chr7:55081920-55085400:1;chr7:55085401-55085400:0;chr7:55085401-55092300:1;chr7:55092301-55092300:0;chr7:55092301-55123400:1;chr7:55123401-55123400:0;chr7:55123401-55129251:1;chr7:55129252-55129251:0;chr7:55129252-55161900:1;chr7:55161901-55161900:0;chr7:55161901-55163646:1;chr7:55163647-55163646:0;chr7:55163647-55164300:1;chr7:55164301-55164300:0;chr7:55164301-55168181:1;chr7:55168182-55168181:0;chr7:55168182-55168362:1;chr7:55168363-55168362:0;chr7:55168363-55169572:1;chr7:55169573-55169572:0;chr7:55169573-55169903:1;chr7:55169904-55169903:0;chr7:55169904-55170121:1;chr7:55170122-55170121:0;chr7:55170122-55190400:1;chr7:55190401-55190400:0;chr7:55190401-55205018:1;chr7:55205019-55205018:0;chr7:55205019-55220004:1;chr7:55220005-55220004:0;chr7:55220005-55221881:1;chr7:55221882-55221881:0;chr7:55221882-55226820:1;chr7:55226821-55226820:0;chr7:55226821-55232583:1;chr7:55232584-55232583:0;chr7:55232584-55301500:1;chr7:55301501-55301500:0;chr7:55301501-55309600:1;chr7:55309601-55309600:0;chr7:55309601-55318500:1;chr7:55318501-55318800:0;chr7:55318801-55319600:1;chr7:55319601-55319600:0;chr7:55319601-55319652:1;chr7:55319653-55319652:0;chr7:55319653-55324034:1;chr7:55324035-55324034:0;chr7:55324035-55469200:1;chr7:55469201-55470200:0;chr7:55470201-62496438:1;chr7:62496439-62496438:0;chr7:62496439-62496509:1;chr7:62496510-62496509:0;chr7:62496510-62498600:1;chr7:62498601-62498600:0;chr7:62498601-62499395:1;chr7:62499396-62499395:0;chr7:62499396-62499809:1;chr7:62499810-62499809:0;chr7:62499810-62500611:1;chr7:62500612-62500611:0;chr7:62500612-62501322:1;chr7:62501323-62501322:0;chr7:62501323-62514100:1;chr7:62514101-62514100:0;chr7:62514101-62514200:1;chr7:62514201-62514200:0;chr7:62514201-62549040:1;chr7:62549041-62549040:0;chr7:62549041-62549700:1;chr7:62549701-62549700:0;chr7:62549701-62554400:1;chr7:62554401-62554400:0;chr7:62554401-62556900:1;chr7:62556901-62556900:0;chr7:62556901-62564588:1;chr7:62564589-62564588:0;chr7:62564589-62570000:1;chr7:62570001-62570000:0;chr7:62570001-62578000:1;chr7:62578001-62578000:0;chr7:62578001-62584786:1;chr7:62584787-62584786:0;chr7:62584787-62616843:1;chr7:62616844-62616843:0;chr7:62616844-62616900:1;chr7:62616901-62616900:0;chr7:62616901-62623500:1;chr7:62623501-62623500:0;chr7:62623501-62625000:1;chr7:62625001-62625000:0;chr7:62625001-62649300:1;chr7:62649301-62649400:0;chr7:62649401-88783140:1;chr7:6705601-20822800:1;chr7:6705601-6705600:0;chr7:88783141-88783140:0;chr7:88783141-89103703:1;chr7:89103704-89103703:0;chr7:89103704-89627796:1;chr7:89627797-89627796:0;chr7:89627797-89628673:1;chr7:89628674-89628673:0;chr7:89628674-89635623:1;chr7:89635624-89635623:0;chr7:89635624-89794190:1;chr7:89794191-89794190:0;chr7:89794191-89970196:1;chr7:89970197-89970196:0;chr7:89970197-90023082:1;chr7:90023083-90023082:0;chr7:90023083-90023600:1;chr7:90023601-90023600:0;chr7:90023601-90026621:1;chr7:90026622-90026621:0;chr7:90026622-90027100:1;chr7:90027101-90027100:0;chr7:90027101-90035500:1;chr7:90035501-90035500:0;chr7:90035501-90036400:1;chr7:90036401-90036400:0;chr7:90036401-90039500:1;chr7:90039501-90039500:0;chr7:90039501-90040018:1;chr7:90040019-90040018:0;chr7:90040019-90045854:1;chr7:90045855-90045854:0;chr7:90045855-90058500:1;chr7:90058501-90058500:0;chr7:90058501-90059200:1;chr7:90059201-90059200:0;chr7:90059201-90059354:1;chr7:90059355-90059354:0;chr7:90059355-90059663:1;chr7:90059664-90059663:0;chr7:90059664-90059800:1;chr7:90059801-90059800:0;chr7:90059801-90061200:1;chr7:90061201-90061200:0;chr7:90061201-90089100:1;chr7:90089101-90089100:0;chr7:90089101-90089600:1;chr7:90089601-90089600:0;chr7:90089601-90446306:1;chr7:90446307-90446306:0;chr7:90446307-90447301:1;chr7:90447302-90447301:0;chr7:90447302-90447684:1;chr7:90447685-90447684:0;chr7:90447685-90858766:1;chr7:90858767-90858766:0;chr7:90858767-90859121:1;chr7:90859122-90859121:0;chr7:90859122-90860791:1;chr7:90860792-90860791:0;chr7:90860792-90861357:1;chr7:90861358-90861357:0;chr7:90861358-90861902:1;chr7:90861903-90861902:0;chr7:90861903-90862044:1;chr7:90862045-90862044:0;chr7:90862045-90919529:1;chr7:90919530-90919529:0;chr7:90919530-90922323:1;chr7:90922324-90922323:0;chr7:90922324-90922566:1;chr7:90922567-90922566:0;chr7:90922567-90948578:1;chr7:90948579-90948578:0;chr7:90948579-91001636:1;chr7:91001637-91001636:0;chr7:91001637-91002500:1;chr7:91002501-91002500:0;chr7:91002501-91035291:1;chr7:91035292-91035291:0;chr7:91035292-91078093:1;chr7:91078094-91078093:0;chr7:91078094-91104306:1;chr7:91104307-91104306:0;chr7:91104307-91106000:1;chr7:91106001-91111700:0;chr7:91111701-91205687:1;chr7:91205688-91205687:0;chr7:91205688-91882897:1;chr7:91882898-91882897:0;chr7:91882898-91886139:1;chr7:91886140-91886139:0;chr7:91886140-91968332:1;chr7:91968333-91968332:0;chr7:91968333-92161106:1;chr7:92161107-92161106:0;chr7:92161107-92412562:1;chr7:92412563-92412562:0;chr7:92412563-92459422:1;chr7:92459423-92459422:0;chr7:92459423-92464998:1;chr7:92464999-92464998:0;chr7:92464999-92518631:1;chr7:92518632-92518631:0;chr7:92518632-92519100:1;chr7:92519101-92519100:0;chr7:92519101-92526180:1;chr7:92526181-92526180:0;chr7:92526181-92547989:1;chr7:92547990-92547989:0;chr7:92547990-92548092:1;chr7:92548093-92548092:0;chr7:92548093-92568133:1;chr7:92568134-92568133:0;chr7:92568134-92576500:1;chr7:92576501-92576500:0;chr7:92576501-92590729:1;chr7:92590730-92590729:0;chr7:92590730-92929683:1;chr7:92929684-92929683:0;chr7:92929684-93044577:1;chr7:93044578-93044577:0;chr7:93044578-93064458:1;chr7:93064459-93064458:0;chr7:93064459-93129715:1;chr7:93129716-93129715:0;chr7:93129716-93275426:1;chr7:93275427-93275426:0;chr7:93275427-93290724:1;chr7:93290725-93290724:0;chr7:93290725-93296700:1;chr7:93296701-93296700:0;chr7:93296701-93296800:1;chr7:93296801-93296800:0;chr7:93296801-93324800:1;chr7:93324801-93324800:0;chr7:93324801-93337970:1;chr7:93337971-93337970:0;chr7:93337971-93359788:1;chr7:93359789-93359788:0;chr7:93359789-93455399:1;chr7:93455400-93455399:0;chr7:93455400-93477576:1;chr7:93477577-93477576:0;chr7:93477577-93496100:1;chr7:93496101-93496100:0;chr7:93496101-93634225:1;chr7:93634226-93634225:0;chr7:93634226-93634279:1;chr7:93634280-93634279:0;chr7:93634280-93634400:1;chr7:93634401-93634400:0;chr7:93634401-93638700:1;chr7:93638701-93638700:0;chr7:93638701-93638900:1;chr7:93638901-93638900:0;chr7:93638901-93639700:1;chr7:93639701-93639700:0;chr7:93639701-93641920:1;chr7:93641921-93641920:0;chr7:93641921-93648000:1;chr7:93648001-93648000:0;chr7:93648001-93648700:1;chr7:93648701-93649400:0;chr7:93649401-93676169:1;chr7:93676170-142329000:1;chr7:93676170-93676169:0;chr8:0-107064781:0;chr8:107064782-107064882:1;chr8:107064883-139372300:0;chr8:139372301-139401500:-1;chr8:139401501-146364022:0;chr9:0-140191022:0;chr9:140191023-141102500:-1;chr9:141102501-141213431:0;chrX:0-32683343:0;chrX:124406001-124412100:-1;chrX:124412101-155270560:0;chrX:32683344-32688542:1;chrX:32688543-124406000:0;chrY:0-2649500:0;chrY:26446401-59373566:0;chrY:2649501-26446400:-1 hs7:91008052-91008052,hs7:55230736-55230736;hs17:12553017-12553017,hs17:12556412-12556412;hs9:140191023-140191023,hs5:156635001-156635001;hs20:43428357-43428357,hs20:56426519-56426519;hs7:55294526-55294526,hs7:93064459-93064459;hs20:56426242-56426242,hs20:44779161-44779161;hs7:62629233-62629233,hs7:55058683-55058683;hs13:61154634-61154634,hs13:96154380-96154380;hs17:10472147-10472147,hs17:10475143-10475143;hs7:54826618-54826618,hs7:54962436-54962436;hs7:62577951-62577951,hs7:55363719-55363719;hs2:3964065-3964065,hs2:6209835-6209835;hs1:194044706-194044706,hs1:195495655-195495655;hs17:9156675-9156675,hs17:9152636-9152636 ABCB5;ADAM22;AKAP9;ANKIB1;BET1;C11orf31;C15orf27;C16orf89;C17orf51;C19orf48;C1GALT1;C1orf168;C1orf94;C20orf85;C3orf38;C4orf32;C7orf26;C7orf28B;C7orf34;C7orf62;C7orf63;C7orf64;CALCR;CASD1;CCDC132;CDCA7L;CDK14;CDK6;CHCHD2;CLDN12;CLEC5A;COBL;COL1A2;CYP51A1;DDC;DNAH11;EGFR;ESYT2;FAM133B;FZD1;GATAD1;GNG11;GNGT1;GPCRLTM7;GRB10;GRID2IP;GTPBP10;HEPACAM2;ITGB8;KDELR2;KRIT1;LANCL2;LOC100288524;LOC389493;LOC646627;LOC647589;LRRD1;MACC1;MRPS17;MTERF;NCAPG2;OR9A4;PDGFA;PEG10;PEX1;PHKG1;POM121L12;PPP1R9A;PRKAR1B;PRSS2;PTPRN2;RAPGEF5;RSPH10B;RSPH10B2;SAMD9;SAMD9L;SEC61G;SEPT14;SGCE;SP4;SP8;SRI;STEAP1;STEAP1B;STEAP2;STEAP4;TAS2R38;TFPI2;TMEM196;TRPV6;VIPR2;VOPP1;VSTM2A;WDR60;ZDHHC4;ZNF12;ZNF479;ZNF679;ZNF680;ZNF713;ZNF716;ZNF727;ZNF735;ZNF736;ZNF804B;ZNF853; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes NA CTDB0392 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 8 Glioma Next Generation Sequencing Homo sapiens SJHGG019_S Illumina Genome Analyzer IIx or HiSeq chr10:0-17221872:0;chr10:135524701-135534747:0;chr10:17221873-17221959:-1;chr10:17221960-37345400:0;chr10:37345401-38192500:1;chr10:38192501-42397400:0;chr10:42397401-58847981:1;chr10:58847982-58847981:0;chr10:58847982-58848265:-1;chr10:58848266-58848265:0;chr10:58848266-84029641:1;chr10:84029642-84029641:0;chr10:84029642-84029794:1;chr10:84029795-135524700:1;chr10:84029795-84029794:0;chr11:0-133700:0;chr11:133701-17226760:1;chr11:134946401-135006516:0;chr11:17226761-17226760:0;chr11:17226761-87552907:1;chr11:87552908-87552907:0;chr11:87552908-92215404:1;chr11:92215405-134946400:1;chr11:92215405-92215404:0;chr12:0-187600:0;chr12:102303201-102303200:0;chr12:102303201-133841500:1;chr12:133841501-133851895:0;chr12:15816523-15816522:0;chr12:15816523-15976421:1;chr12:15976422-15976421:0;chr12:15976422-73334844:1;chr12:187601-15816522:1;chr12:73334845-73334844:0;chr12:73334845-73335347:1;chr12:73335348-102303200:1;chr12:73335348-73335347:0;chr13:0-19020700:0;chr13:115109801-115169878:0;chr13:19020701-84759402:1;chr13:84759403-84759402:0;chr13:84759403-84759665:1;chr13:84759666-115109800:1;chr13:84759666-84759665:0;chr14:0-20160900:0;chr14:107289501-107349540:0;chr14:20160901-22314500:1;chr14:22314501-22314500:0;chr14:22314501-22973300:1;chr14:22973301-22973500:0;chr14:22973501-41517904:1;chr14:41517905-41517904:0;chr14:41517905-41517995:-1;chr14:41517996-41517995:0;chr14:41517996-86016606:1;chr14:86016607-87381885:0;chr14:87381886-107289500:1;chr15:0-20000000:0;chr15:100797601-100797600:0;chr15:100797601-102465300:1;chr15:102465301-102531392:0;chr15:20000001-20112000:1;chr15:20112001-20113600:0;chr15:20113601-20195100:1;chr15:20195101-35116500:0;chr15:35116501-35231000:1;chr15:35231001-36528500:0;chr15:36528501-36867536:1;chr15:36867537-36869238:0;chr15:36869239-36873388:1;chr15:36873389-36873388:0;chr15:36873389-36873787:1;chr15:36873788-36873787:0;chr15:36873788-36882500:1;chr15:36882501-42151795:0;chr15:42151796-42157409:1;chr15:42157410-42161525:0;chr15:42161526-56072428:1;chr15:56072429-56072428:0;chr15:56072429-88756068:1;chr15:88756069-88756068:0;chr15:88756069-95148800:1;chr15:95148801-95148800:0;chr15:95148801-96034976:1;chr15:96034977-96034976:0;chr15:96034977-99776023:1;chr15:99776024-100797600:1;chr15:99776024-99776023:0;chr16:0-60000:0;chr16:32579628-32602840:0;chr16:32602841-47817562:1;chr16:47817563-47817562:0;chr16:47817563-56970744:1;chr16:56970745-56970744:0;chr16:56970745-56970761:1;chr16:56970762-56970761:0;chr16:56970762-57021623:1;chr16:57021624-70883400:0;chr16:60001-32579627:1;chr16:70883401-71202600:1;chr16:71202601-90354753:0;chr17:0-9152635:0;chr17:10472147-10472146:0;chr17:10472147-12553016:1;chr17:12553017-12553016:0;chr17:12553017-12556411:1;chr17:12556412-12556411:0;chr17:12556412-21547300:1;chr17:21547301-21666600:0;chr17:21666601-22244500:1;chr17:22244501-25341900:0;chr17:25341901-47563457:1;chr17:47563458-54461900:0;chr17:54461901-54475403:1;chr17:54475404-54475403:0;chr17:54475404-81195100:1;chr17:81195101-81195210:0;chr17:9152636-9156674:1;chr17:9156675-10472146:1;chr17:9156675-9156674:0;chr18:0-46100:0;chr18:15390901-18510900:0;chr18:18510901-33125000:1;chr18:33125001-33125000:0;chr18:33125001-33730996:1;chr18:33730997-33730996:0;chr18:33730997-33732118:1;chr18:33732119-33732118:0;chr18:33732119-78017200:1;chr18:46101-15390900:1;chr18:78017201-78077248:0;chr19:0-89200:0;chr19:51211401-51211400:0;chr19:51211401-59118800:1;chr19:59118801-59128983:0;chr19:89201-51211400:1;chr1:0-10100:0;chr1:10101-15548769:1;chr1:104103501-104103500:0;chr1:104103501-109840900:1;chr1:109840901-109840900:0;chr1:109840901-181461280:1;chr1:15548770-15548769:0;chr1:15548770-16786988:1;chr1:16786989-16786988:0;chr1:16786989-57814198:1;chr1:181461281-181461280:0;chr1:181461281-181561000:1;chr1:181561001-181561000:0;chr1:181561001-181716968:1;chr1:181716969-181716968:0;chr1:181716969-181786100:1;chr1:181786101-181786100:0;chr1:181786101-221362400:1;chr1:221362401-221362400:0;chr1:221362401-221443535:1;chr1:221443536-221443535:0;chr1:221443536-249240500:1;chr1:249240501-249250621:0;chr1:57814199-57814198:0;chr1:57814199-58253800:1;chr1:58253801-58253800:0;chr1:58253801-65425645:1;chr1:65425646-65425645:0;chr1:65425646-74159348:1;chr1:74159349-74159348:0;chr1:74159349-74160442:1;chr1:74160443-74160442:0;chr1:74160443-74173368:1;chr1:74173369-74173368:0;chr1:74173369-89020239:1;chr1:89020240-89020239:0;chr1:89020240-91330205:1;chr1:91330206-91330205:0;chr1:91330206-97525031:1;chr1:97525032-104103500:1;chr1:97525032-97525031:0;chr20:0-60000:0;chr20:24961257-24963319:0;chr20:24963320-24963563:1;chr20:24963564-29804200:0;chr20:29804201-42178022:1;chr20:42178023-42312200:0;chr20:42312201-43428141:1;chr20:43428142-43428141:0;chr20:43428142-43428356:1;chr20:43428357-43428356:0;chr20:43428357-43432880:1;chr20:43432881-43432880:0;chr20:43432881-43648400:1;chr20:43648401-43683190:0;chr20:43683191-43685448:1;chr20:43685449-44779160:0;chr20:44779161-44779459:1;chr20:44779460-44779459:0;chr20:44779460-44821300:1;chr20:44821301-44895984:0;chr20:44895985-44896199:1;chr20:44896200-45052769:0;chr20:45052770-55921500:1;chr20:55921501-56241001:0;chr20:56241002-56241290:1;chr20:56241291-56416900:0;chr20:56416901-56426241:1;chr20:56426242-56426241:0;chr20:56426242-56426355:1;chr20:56426356-56426355:0;chr20:56426356-56426519:1;chr20:56426520-56426519:0;chr20:56426520-56426567:1;chr20:56426568-56426567:0;chr20:56426568-56427143:1;chr20:56427144-56427143:0;chr20:56427144-56427397:1;chr20:56427398-63025520:0;chr20:60001-24961256:1;chr21:0-14441400:0;chr21:14441401-48119800:1;chr21:48119801-48129895:0;chr22:0-16847900:0;chr22:16847901-36396048:1;chr22:36396049-36396048:0;chr22:36396049-36402812:1;chr22:36402813-36402812:0;chr22:36402813-51234500:1;chr22:51234501-51304566:0;chr2:0-10000:0;chr2:10001-54567500:1;chr2:213033608-213033607:0;chr2:213033608-213143984:1;chr2:213143985-213143984:0;chr2:213143985-223869957:1;chr2:223869958-223869957:0;chr2:223869958-243183600:1;chr2:243183601-243199373:0;chr2:54567501-213033607:1;chr2:54567501-54567500:0;chr3:0-60200:0;chr3:11023088-11023171:0;chr3:11023172-68592878:1;chr3:114011942-114011941:0;chr3:114011942-114347253:1;chr3:114347254-114347253:0;chr3:114347254-180412200:1;chr3:180412201-180412200:0;chr3:180412201-197948400:1;chr3:197948401-198022430:0;chr3:60201-11023087:1;chr3:68592879-68592878:0;chr3:68592879-68593700:1;chr3:68593701-68593700:0;chr3:68593701-68596373:1;chr3:68596374-68596696:0;chr3:68596697-81523594:1;chr3:81523595-81523594:0;chr3:81523595-81523857:1;chr3:81523858-81523857:0;chr3:81523858-85752622:1;chr3:85752623-114011941:1;chr3:85752623-85752622:0;chr4:0-68500:0;chr4:116177762-116223428:-1;chr4:116223429-132920200:0;chr4:132920201-133226945:1;chr4:133226946-133287075:0;chr4:133287076-133333980:1;chr4:133333981-133339395:0;chr4:133339396-133342000:1;chr4:133342001-133347100:0;chr4:133347101-133361987:1;chr4:133361988-134224511:0;chr4:134224512-134410206:1;chr4:134410207-150670753:0;chr4:150670754-151617933:1;chr4:151617934-152100900:0;chr4:152100901-164411524:1;chr4:164411525-164413241:0;chr4:164413242-177970200:1;chr4:177970201-177979100:0;chr4:177979101-178055300:1;chr4:178055301-178056025:0;chr4:178056026-178057781:1;chr4:178057782-178058243:0;chr4:178058244-178062329:1;chr4:178062330-178140943:0;chr4:178140944-178141898:1;chr4:178141899-180207816:0;chr4:180207817-184302918:1;chr4:184302919-184307822:0;chr4:184307823-184311868:1;chr4:184311869-184313574:0;chr4:184313575-184871341:1;chr4:184871342-191154276:0;chr4:49659701-52680900:0;chr4:52680901-82986600:1;chr4:5373793-5373792:0;chr4:5373793-5374098:1;chr4:5374099-5374098:0;chr4:5374099-8515933:1;chr4:68501-5373792:1;chr4:82986601-116177761:0;chr4:8515934-8515933:0;chr4:8515934-8666821:1;chr4:8666822-49659700:1;chr4:8666822-8666821:0;chr5:0-11700:0;chr5:11701-20573885:1;chr5:124201805-124201804:0;chr5:124201805-147125774:1;chr5:147125775-147125774:0;chr5:147125775-147125856:1;chr5:147125857-147125856:0;chr5:147125857-156635000:1;chr5:156635001-156635000:0;chr5:156635001-156635583:1;chr5:156635584-156635583:0;chr5:156635584-158483014:1;chr5:158483015-158483014:0;chr5:158483015-180736100:1;chr5:180736101-180915260:0;chr5:20573886-20573885:0;chr5:20573886-20574128:1;chr5:20574129-20574128:0;chr5:20574129-39732051:1;chr5:39732052-39732051:0;chr5:39732052-40087311:1;chr5:40087312-40087311:0;chr5:40087312-61612007:1;chr5:61612008-61612007:0;chr5:61612008-61734334:1;chr5:61734335-61734334:0;chr5:61734335-63546617:1;chr5:63546618-63546617:0;chr5:63546618-63551200:1;chr5:63551201-63553500:0;chr5:63553501-124201804:1;chr6:0-90700:0;chr6:140060884-140060883:0;chr6:140060884-140063017:1;chr6:140063018-140063017:0;chr6:140063018-171050900:1;chr6:171050901-171115067:0;chr6:42500601-42500900:0;chr6:42500901-42576021:1;chr6:42576022-42576021:0;chr6:42576022-45083703:1;chr6:45083704-45083703:0;chr6:45083704-45571126:1;chr6:45571127-45571126:0;chr6:45571127-45572654:1;chr6:45572655-45572654:0;chr6:45572655-45600595:1;chr6:45600596-45600595:0;chr6:45600596-46496900:1;chr6:46496901-46496900:0;chr6:46496901-48931024:1;chr6:48931025-48931024:0;chr6:48931025-48934679:1;chr6:48934680-48934679:0;chr6:48934680-48969494:1;chr6:48969495-48969494:0;chr6:48969495-49465421:1;chr6:49465422-49465421:0;chr6:49465422-49467517:1;chr6:49467518-49467517:0;chr6:49467518-51366462:1;chr6:51366463-51366462:0;chr6:51366463-57016300:1;chr6:57016301-57016300:0;chr6:57016301-94072200:1;chr6:90701-42500600:1;chr6:94072201-94072200:0;chr6:94072201-95680500:1;chr6:95680501-95830800:0;chr6:95830801-140060883:1;chr7:0-10000:0;chr7:10001-397742:1;chr7:134056000-134055999:0;chr7:134056000-134059162:1;chr7:134059163-134059162:0;chr7:134059163-142042600:1;chr7:13884466-13884465:0;chr7:13884466-13884856:1;chr7:13884857-13884856:0;chr7:13884857-37798800:1;chr7:142042601-142098200:0;chr7:142098201-142425600:1;chr7:142425601-142425700:0;chr7:142425701-145177165:1;chr7:145177166-145177165:0;chr7:145177166-145177258:1;chr7:145177259-145177258:0;chr7:145177259-159128500:1;chr7:159128501-159138663:0;chr7:3673868-3673867:0;chr7:3673868-3690125:1;chr7:3690126-3690125:0;chr7:3690126-3724500:1;chr7:3724501-3724500:0;chr7:3724501-4879345:1;chr7:37798801-37798800:0;chr7:37798801-39535534:1;chr7:39535535-39535534:0;chr7:39535535-39591000:1;chr7:39591001-39591131:0;chr7:39591132-39603167:1;chr7:39603168-39603167:0;chr7:39603168-39603300:1;chr7:39603301-39603300:0;chr7:39603301-39674578:1;chr7:39674579-39674578:0;chr7:39674579-39956621:1;chr7:397743-397742:0;chr7:397743-403207:1;chr7:39956622-39956621:0;chr7:39956622-39961253:1;chr7:39961254-39961253:0;chr7:39961254-41068030:1;chr7:403208-403207:0;chr7:403208-404310:1;chr7:404311-3673867:1;chr7:404311-404310:0;chr7:41068031-41068030:0;chr7:41068031-41071100:1;chr7:41071101-41071100:0;chr7:41071101-41071400:1;chr7:41071401-41071400:0;chr7:41071401-41073400:1;chr7:41073401-41073400:0;chr7:41073401-41085122:1;chr7:41085123-41085122:0;chr7:41085123-41085275:1;chr7:41085276-41085275:0;chr7:41085276-41092963:1;chr7:41092964-41092963:0;chr7:41092964-41095103:1;chr7:41095104-41095103:0;chr7:41095104-41965018:1;chr7:41965019-41965018:0;chr7:41965019-42079010:1;chr7:42079011-42079010:0;chr7:42079011-42394123:1;chr7:42394124-42394123:0;chr7:42394124-42395788:1;chr7:42395789-42395788:0;chr7:42395789-42486017:1;chr7:42486018-42486017:0;chr7:42486018-42684292:1;chr7:42684293-42684292:0;chr7:42684293-42743499:1;chr7:42743500-42743499:0;chr7:42743500-42770579:1;chr7:42770580-42770579:0;chr7:42770580-42781022:1;chr7:42781023-42781022:0;chr7:42781023-42794272:1;chr7:42794273-42794272:0;chr7:42794273-42830632:1;chr7:42830633-42830632:0;chr7:42830633-42937960:1;chr7:42937961-42937960:0;chr7:42937961-44288166:1;chr7:44288167-44288166:0;chr7:44288167-47176911:1;chr7:47176912-47176911:0;chr7:47176912-47817900:1;chr7:47817901-47817900:0;chr7:47817901-54770443:1;chr7:4879346-4879345:0;chr7:4879346-4879400:1;chr7:4879401-4879400:0;chr7:4879401-7999531:1;chr7:54770444-54770443:0;chr7:54770444-54826562:1;chr7:54826563-54826562:0;chr7:54826563-54946712:1;chr7:54946713-54946712:0;chr7:54946713-54947455:1;chr7:54947456-54947455:0;chr7:54947456-55260500:1;chr7:55260501-55260500:0;chr7:55260501-55342518:1;chr7:55342519-55342518:0;chr7:55342519-55355327:1;chr7:55355328-55355327:0;chr7:55355328-55469200:1;chr7:55469201-55470200:0;chr7:55470201-62496426:1;chr7:62496427-62496426:0;chr7:62496427-62498774:1;chr7:62498775-62498774:0;chr7:62498775-62649300:1;chr7:62649301-62649400:0;chr7:62649401-64689800:1;chr7:64689801-64689800:0;chr7:64689801-64780500:1;chr7:64780501-64780500:0;chr7:64780501-64978900:1;chr7:64978901-65150000:0;chr7:65150001-66597800:1;chr7:66597801-66598500:0;chr7:66598501-91631377:1;chr7:7999532-7999531:0;chr7:7999532-8004386:1;chr7:8004387-13884465:1;chr7:8004387-8004386:0;chr7:91631378-91631377:0;chr7:91631378-91670300:1;chr7:91670301-91670300:0;chr7:91670301-91691318:1;chr7:91691319-91691318:0;chr7:91691319-91978293:1;chr7:91978294-91978293:0;chr7:91978294-91995400:1;chr7:91995401-91995400:0;chr7:91995401-92099700:1;chr7:92099701-92099900:0;chr7:92099901-92101200:1;chr7:92101201-92101700:0;chr7:92101701-92216206:1;chr7:92216207-92216206:0;chr7:92216207-92394700:1;chr7:92394701-92394700:0;chr7:92394701-92455200:1;chr7:92455201-92455200:0;chr7:92455201-92537103:1;chr7:92537104-92537103:0;chr7:92537104-92537180:1;chr7:92537181-134055999:1;chr7:92537181-92537180:0;chr8:0-100700:0;chr8:100701-1902999:1;chr8:112339949-112339948:0;chr8:112339949-112341974:1;chr8:112341975-112341974:0;chr8:112341975-127211664:1;chr8:127211665-127211664:0;chr8:127211665-128287339:1;chr8:128287340-128287339:0;chr8:128287340-128304700:1;chr8:128304701-128304700:0;chr8:128304701-128736394:1;chr8:128736395-128736394:0;chr8:128736395-128839822:1;chr8:128839823-128839822:0;chr8:128839823-129168589:1;chr8:129168590-129168589:0;chr8:129168590-129265695:1;chr8:129265696-129265695:0;chr8:129265696-146303800:1;chr8:146303801-146364022:0;chr8:1903000-1902999:0;chr8:1903000-1911256:1;chr8:1911257-1911256:0;chr8:1911257-1925613:1;chr8:1925614-1925613:0;chr8:1925614-4480521:1;chr8:35057647-35060057:0;chr8:35060058-66281842:1;chr8:4480522-4480521:0;chr8:4480522-5903513:1;chr8:5903514-5903513:0;chr8:5903514-7105800:1;chr8:66281843-66281955:0;chr8:66281956-89148639:1;chr8:7105801-8094600:0;chr8:8094601-8628100:1;chr8:8628101-8628100:0;chr8:8628101-9852837:1;chr8:89148640-89148639:0;chr8:89148640-94184797:1;chr8:94184798-94184797:0;chr8:94184798-94883970:1;chr8:94883971-94883970:0;chr8:94883971-94896665:1;chr8:94896666-94896665:0;chr8:94896666-95049200:1;chr8:95049201-95049393:0;chr8:95049394-95059152:1;chr8:95059153-95059152:0;chr8:95059153-95082000:1;chr8:95082001-95082000:0;chr8:95082001-95097862:1;chr8:95097863-95097862:0;chr8:95097863-95364379:1;chr8:95364380-95364379:0;chr8:95364380-95382763:1;chr8:95382764-95382763:0;chr8:95382764-95423222:1;chr8:95423223-95423222:0;chr8:95423223-95430816:1;chr8:95430817-95430816:0;chr8:95430817-97225800:1;chr8:97225801-97225800:0;chr8:97225801-97239281:1;chr8:97239282-97239281:0;chr8:97239282-97239637:1;chr8:97239638-97239637:0;chr8:97239638-97282701:1;chr8:97282702-97282701:0;chr8:97282702-97283263:1;chr8:97283264-97283263:0;chr8:97283264-97297938:1;chr8:97297939-97297938:0;chr8:97297939-97301423:1;chr8:97301424-97301423:0;chr8:97301424-97311302:1;chr8:97311303-97311302:0;chr8:97311303-97311935:1;chr8:97311936-112339948:1;chr8:97311936-97311935:0;chr8:9852838-35057646:1;chr8:9852838-9852837:0;chr9:0-10000:0;chr9:10001-12318931:1;chr9:12318932-12319005:0;chr9:12319006-86624275:1;chr9:140191023-141213431:0;chr9:86624276-86624275:0;chr9:86624276-86624538:1;chr9:86624539-140191022:1;chr9:86624539-86624538:0;chrX:0-2699500:0;chrX:154930301-155270560:0;chrX:26489301-26489300:0;chrX:26489301-27363200:1;chrX:2699501-26489300:1;chrX:27363201-27363200:0;chrX:27363201-31409800:1;chrX:31409801-31409904:0;chrX:31409905-31468246:1;chrX:31468247-31468246:0;chrX:31468247-32683343:1;chrX:32683344-32683343:0;chrX:32683344-32688542:1;chrX:32688543-32688542:0;chrX:32688543-56147300:1;chrX:56147301-56147600:0;chrX:56147601-85001100:1;chrX:85001101-85001100:0;chrX:85001101-85052900:1;chrX:85052901-154930300:1;chrX:85052901-85052900:0;chrY:0-2649500:0;chrY:2649501-28817600:-1;chrY:28817601-59373566:0 hs1:181716969-181716969,hs1:181461281-181461281;hs1:74173369-74173369,hs6:48931025-48931025;hs2:223869958-223869958,hs8:8628139-8628139;hs3:85752623-85752623,hs11:17226761-17226761;hs4:184302919-184302919,hs8:97239638-97239638;hs4:178055347-178055347,hs8:97282702-97282702;hs5:2250578-2250578,hs13:84759403-84759403;hs5:150132011-150132011,hs12:129453521-129453521;hs5:124201805-124201805,hs3:68593657-68593657;hs5:32192385-32192385,hs5:32405980-32405980;hs5:150132011-150132011,hs12:129453521-129453521;hs6:48934680-48934680,hs1:89020240-89020240;hs6:45571127-45571127,hs1:97525032-97525032;hs6:42576022-42576022,hs6:51366463-51366463;hs7:39603168-39603168,hs7:39535535-39535535;hs7:91691319-91691319,hs8:129168586-129168586;hs7:62514867-62514867,hs12:15976422-15976422;hs7:3690126-3690126,hs7:404311-404311;hs7:7999532-7999532,hs7:8004387-8004387;hs7:42415834-42415834,hs7:42394124-42394124;hs7:92056324-92056324,hs7:42717665-42717665;hs7:42794273-42794273,hs7:41965019-41965019;hs7:44288167-44288167,hs19:48976482-48976482;hs7:91997783-91997783,hs8:5903514-5903514;hs7:91691319-91691319,hs8:129168587-129168587;hs7:41088159-41088159,hs7:42712374-42712374;hs7:3673868-3673868,hs12:16995828-16995828;hs7:42712397-42712397,hs17:64385441-64385441;hs7:92423930-92423930,hs7:92395481-92395481;hs7:51777943-51777943,hs2:170341974-170341974;hs7:91691319-91691319,hs8:129168590-129168590;hs7:42032102-42032102,hs7:41085123-41085123;hs8:97379485-97379485,hs4:152147469-152147469;hs8:129024611-129024611,hs7:39612374-39612374;hs8:1925614-1925614,hs8:95382764-95382764;hs8:97301424-97301424,hs4:184307823-184307823;hs8:97297939-97297939,hs4:184313575-184313575;hs8:28058186-28058186,hs13:85623998-85623998;hs8:8468012-8468012,hs7:42036986-42036986;hs8:26350106-26350106,hs7:42879785-42879785;hs8:128951821-128951821,hs7:39603492-39603492;hs8:28058434-28058434,hs13:85624018-85624018;hs8:129024611-129024611,hs7:39612374-39612374;hs8:97311936-97311936,hs4:164413242-164413242;hs8:129008674-129008674,hs7:42797217-42797217;hs8:81164588-81164588,hs10:83831880-83831880;hs11:87223963-87223963,hs3:34314111-34314111;hs11:127418984-127418984,hs11:96254752-96254752;hs11:10103773-10103773,hsX:9610223-9610223;hs11:79901987-79901987,hs13:68684461-68684461;hs12:129453510-129453510,hs5:150132014-150132014;hs12:129453510-129453510,hs5:150132014-150132014;hs12:10179317-10179317,hs11:77278835-77278835;hs13:68684454-68684454,hs11:79902046-79902046;hs13:49146126-49146126,hs17:55056482-55056482;hs13:84759666-84759666,hs5:2250590-2250590;hs13:49146126-49146126,hs17:55056480-55056480;hs15:93412020-93412020,hs15:99776024-99776024;hs15:60700052-60700052,hs7:91945193-91945193;hs16:5773544-5773544,hs20:58400075-58400075;hs16:56970762-56970762,hs16:5773545-5773545;hs16:56970745-56970745,hs20:58400075-58400075;hs17:13414803-13414803,hs16:47817563-47817563;hs17:64385439-64385439,hs7:42712396-42712396;hs18:73600343-73600343,hs14:25325335-25325335;hs18:22650240-22650240,hs18:25130203-25130203;hs19:14049147-14049147,hs2:19444657-19444657;hs19:14048939-14048939,hs2:73738939-73738939;hs22:36402813-36402813,hs15:56072429-56072429;hs22:36402813-36402813,hs15:56072426-56072426;hs22:31514293-31514293,hs22:36396049-36396049 ADCY8;AGPAT5;ANGPT2;ARMC1;ASAP1;B7H6;BHLHE22;C10orf99;C11orf58;C14orf28;C15orf32;C15orf41;C16orf58;C17orf51;C18orf21;C19orf48;C1orf115;C1orf168;C2orf73;C3orf30;C5orf46;C5orf64;C6orf132;C6orf141;C7orf25;C7orf65;C7orf69;C8orf33;C8orf37;C8orf38;C8orf41;C8orf42;C8orf74;C8orf83;C9orf173;C9orf64;C9orf66;CDH17;CLDN23;CNBD1;CNGB3;COMMD5;CPNE3;CSMD1;CSMD3;CXorf21;CYP7B1;DCAF4L2;DECR1;DEFA1;DEFA1B;DEFA3;DEFA4;DEFA5;DEFB1;DNAJC5B;DPY19L4;DUSP26;EBAG9;EFR3A;EIF3H;ENY2;ERI1;ERLIN2;ESRP1;FAM49B;FAM84B;FAM92A1;FBXO25;FLJ27352;FUT10;GDF6;GGH;GPCRLTM7;GSDMC;INTS8;KCNU1;KCNV1;KIAA0196;KIAA1429;LOC100287718;LOC100288524;LOC342918;LOC389493;LOC389676;LOC646627;LOC647589;LOC653486;LOC653550;LOC728379;LOC728393;LRRC69;MAK16;MCPH1;MFHAS1;MMP16;MSRA;MTDH;MTERFD1;MTFR1;MYC;MYOM2;NBN;NSMCE2;OR4F21;OSGIN2;PDE7A;PDP1;PGCP;PKHD1L1;PLEKHF2;POU5F1B;PPP1R3B;PROSC;PRSS55;PTDSS1;PVT1;RAD21;RAD54B;RBM12B;RIPK2;RNF122;RP1L1;RUNX1T1;SDC2;SGK223;SLC26A7;SOX7;SQLE;SYBU;TMEM67;TNKS;TP53INP1;TRIB1;TRIM55;TRPS1;TSPYL5;TTPA;UNC5D;UQCRB;UTP23;XKR5;YTHDF3;ZNF16;ZNF250;ZNF572;ZNF596;ZNF7;ZNF703; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes MMP16,TRAPPC9 CTDB0393 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 11 Glioma Next Generation Sequencing Homo sapiens SJHGG033_D Illumina Genome Analyzer IIx or HiSeq chr10:0-71700:0;chr10:133126601-133126600:0;chr10:133126601-133615420:-1;chr10:133615421-133615420:0;chr10:133615421-135524700:-1;chr10:135524701-135534747:0;chr10:71701-133126600:-1;chr11:0-133700:0;chr11:133701-43535100:-1;chr11:43535101-43803997:0;chr11:43803998-43806013:-1;chr11:43806014-44233709:0;chr11:44233710-44256240:-1;chr11:44256241-44309731:0;chr11:44309732-44311714:-1;chr11:44311715-44490058:0;chr11:44490059-44491110:-1;chr11:44491111-49321300:0;chr11:49321301-49324802:-1;chr11:49324803-49342700:0;chr11:49342701-49344600:-1;chr11:49344601-49469784:0;chr11:49469785-49473400:-1;chr11:49473401-49709800:0;chr11:49709801-49709900:-1;chr11:49709901-49872900:0;chr11:49872901-49873797:-1;chr11:49873798-50039400:0;chr11:50039401-50783300:-1;chr11:50783301-51478200:0;chr11:51478201-51479700:-1;chr11:51479701-56855245:0;chr11:56855246-56856221:-1;chr11:56856222-57196584:0;chr11:57196585-57199328:-1;chr11:57199329-78658239:0;chr11:78658240-78661352:-1;chr11:78661353-78757193:0;chr11:78757194-78776707:-1;chr11:78776708-78789380:0;chr11:78789381-78789707:-1;chr11:78789708-79224347:0;chr11:79224348-79235886:-1;chr11:79235887-80667820:0;chr11:80667821-80669032:-1;chr11:80669033-80904687:0;chr11:80904688-80905811:-1;chr11:80905812-80942176:0;chr11:80942177-80943341:-1;chr11:80943342-81112000:0;chr11:81112001-81119896:-1;chr11:81119897-81122119:0;chr11:81122120-81123236:-1;chr11:81123237-81160000:0;chr11:81160001-81164674:-1;chr11:81164675-81199018:0;chr11:81199019-81229211:-1;chr11:81229212-81456001:0;chr11:81456002-81458951:-1;chr11:81458952-81489473:0;chr11:81489474-81494346:-1;chr11:81494347-81520322:0;chr11:81520323-81592978:-1;chr11:81592979-81605192:0;chr11:81605193-81610465:-1;chr11:81610466-81687160:0;chr11:81687161-81707288:-1;chr11:81707289-81739100:0;chr11:81739101-81852600:-1;chr11:81852601-81919900:0;chr11:81919901-81938638:-1;chr11:81938639-81950281:0;chr11:81950282-81951632:1;chr11:81951633-81982600:0;chr11:81982601-82054200:-1;chr11:82054201-82066681:0;chr11:82066682-82071205:-1;chr11:82071206-82117676:0;chr11:82117677-82119116:-1;chr11:82119117-82129510:0;chr11:82129511-82130653:-1;chr11:82130654-82256487:0;chr11:82256488-82258654:-1;chr11:82258655-82266651:0;chr11:82266652-82273666:-1;chr11:82273667-82341040:0;chr11:82341041-82341400:-1;chr11:82341401-82359753:0;chr11:82359754-82362251:-1;chr11:82362252-82415113:0;chr11:82415114-82428443:-1;chr11:82428444-82479476:0;chr11:82479477-82481098:-1;chr11:82481099-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-247833258:0;chr1:247833259-248280226:-1;chr1:248280227-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-10000:0;chr2:10001-243183600:1;chr2:243183601-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-11700:0;chr5:11701-1237096:-1;chr5:1237097-1302234:0;chr5:1302235-1303753:-1;chr5:1303754-1336451:0;chr5:1336452-1337151:-1;chr5:1337152-1383086:0;chr5:1383087-1604200:-1;chr5:14514082-14514313:1;chr5:14514314-26870466:0;chr5:1604201-1706671:0;chr5:1706672-1707434:-1;chr5:1707435-1727784:0;chr5:1727785-1729176:-1;chr5:1729177-1817305:0;chr5:1817306-1819919:-1;chr5:1819920-14514081:0;chr5:26870467-26871530:-1;chr5:26871531-27288159:0;chr5:27288160-27290181:-1;chr5:27290182-27297282:0;chr5:27297283-27297778:-1;chr5:27297779-27434368:0;chr5:27434369-27435554:-1;chr5:27435555-27442287:0;chr5:27442288-27443958:-1;chr5:27443959-27462573:0;chr5:27462574-27463904:-1;chr5:27463905-27545232:0;chr5:27545233-27546306:-1;chr5:27546307-27547179:0;chr5:27547180-27551462:-1;chr5:27551463-27741690:0;chr5:27741691-27742981:-1;chr5:27742982-27802800:0;chr5:27802801-27827200:-1;chr5:27827201-27905811:0;chr5:27905812-31416789:-1;chr5:31416790-31465404:0;chr5:31465405-31501808:-1;chr5:31501809-31521054:0;chr5:31521055-31543284:-1;chr5:31543285-31577003:0;chr5:31577004-31578807:-1;chr5:31578808-31579608:0;chr5:31579609-31580016:-1;chr5:31580017-31585352:0;chr5:31585353-31594600:-1;chr5:31594601-31667400:0;chr5:31667401-31667639:-1;chr5:31667640-31669032:0;chr5:31669033-31673193:-1;chr5:31673194-31679937:0;chr5:31679938-31683039:-1;chr5:31683040-32316983:0;chr5:32316984-32318500:-1;chr5:32318501-180915260:0;chr6:0-171115067:0;chr7:0-22573900:0;chr7:142327601-142494500:1;chr7:142494501-159138663:0;chr7:22573901-23074600:-1;chr7:23074601-142327600:0;chr8:0-146364022:0;chr9:0-21815670:0;chr9:21815671-21873127:-1;chr9:21873128-21873638:0;chr9:21873639-22208701:-1;chr9:22208702-38642890:0;chr9:38642891-38643842:1;chr9:38643843-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs5:31579609-31579609,hs11:57199329-57199329;hs5:31416790-31416790,hs5:1237097-1237097;hs5:1302235-1302235,hs11:82481099-82481099;hs5:31579609-31579609,hs11:57199330-57199330;hs8:114833218-114833218,hs8:114832069-114832069;hs9:38643843-38643843,hs9:44357162-44357162;hs11:78904762-78904762,hs11:78776708-78776708;hs11:55258222-55258222,hs5:32316984-32316984;hs11:56856222-56856222,hs11:49840025-49840025;hs11:49324803-49324803,hs11:44491111-44491111;hs11:78904762-78904762,hs11:78776708-78776708;hs11:79022285-79022285,hs5:31502398-31502398;hs11:49835295-49835295,hs11:81605193-81605193;hs11:57196585-57196585,hs5:27434367-27434367;hs11:49732378-49732378,hs5:31673194-31673194;hs11:82342498-82342498,hs11:81164675-81164675;hs11:79022285-79022285,hs5:31502398-31502398;hs11:79022285-79022285,hs5:31502398-31502398;hs11:81687161-81687161,hs5:31577004-31577004;hs11:44490059-44490059,hs11:80667821-80667821 ALX4;API5;BET1L;C11orf74;C5orf22;EXT2;GAB2;HSD17B12;LOC653486;LRRC4C;ODF3;ODZ4;RAG2;RIC8A;SCGB1C1;TTC17; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes DROSHA,ODZ4;ODZ4,GAB2 CTDB0394 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 11 Glioma Next Generation Sequencing Homo sapiens SJHGG033_R Illumina Genome Analyzer IIx or HiSeq chr10:0-135534747:0;chr11:0-44309731:0;chr11:44309732-44311714:-1;chr11:44311715-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-14514081:0;chr5:14514082-14514313:1;chr5:14514314-27664485:0;chr5:27664486-27667031:-1;chr5:27667032-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-146364022:0;chr9:0-21815670:0;chr9:21815671-21873127:-1;chr9:21873128-21873638:0;chr9:21873639-22208701:-1;chr9:22208702-38668798:0;chr9:38668799-38668900:-1;chr9:38668901-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs1:59487649-59487649,hs1:59486603-59486603;hs5:27741691-27741691,hs11:81950282-81950282;hs5:31501809-31501809,hs5:27290182-27290182;hs5:1817306-1817306,hs11:78661353-78661353;hs5:26871531-26871531,hs11:80669033-80669033;hs5:27545233-27545233,hs11:78684758-78684758;hs5:27664486-27664486,hs11:43546379-43546379;hs5:31579055-31579055,hs5:27742982-27742982;hs6:37112618-37112618,hs6:37113534-37113534;hs9:38668799-38668799,hs9:40612047-40612047;hs9:21815270-21815270,hs9:45680204-45680204;hs9:22208702-22208702,hs9:21873128-21873128;hs9:38668945-38668945,hs9:38642891-38642891;hs9:7747590-7747590,hs9:7748055-7748055;hs11:81520323-81520323,hs11:82117677-82117677;hs11:79224348-79224348,hs11:82359754-82359754;hs11:57196585-57196585,hs5:27434369-27434369;hs11:82273667-82273667,hs11:78385377-78385377;hs11:51477878-51477878,hs5:27443959-27443959;hs11:81458952-81458952,hs11:81256568-81256568;hs11:78776708-78776708,hs11:78904762-78904762;hs11:82055697-82055697,hs11:43806014-43806014;hs11:81592979-81592979,hs11:82341655-82341655;hs11:79021519-79021519,hs11:49473546-49473546;hs11:82341041-82341041,hs5:31667640-31667640;hs11:51419319-51419319,hs11:82129511-82129511;hs11:78776708-78776708,hs11:78904762-78904762;hs11:79022285-79022285,hs5:31502397-31502397;hs11:79022285-79022285,hs5:31502397-31502397;hs11:78336914-78336914,hs5:31502387-31502387;hs11:80905812-80905812,hs11:50013811-50013811;hs11:80667821-80667821,hs11:44490059-44490059;hs11:81164675-81164675,hs11:82342498-82342498;hs22:34760397-34760397,hs22:34758774-34758774 ALX4;HSD17B12;ODZ4; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes DROSHA,ODZ4 CTDB0395 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 11 Glioma Next Generation Sequencing Homo sapiens SJHGG044_D Illumina Genome Analyzer IIx or HiSeq chr10:0-590762:0;chr10:113717960-113718856:1;chr10:113718857-135534747:0;chr10:36216901-36217358:1;chr10:36217359-113717959:0;chr10:590763-591339:1;chr10:591340-36216900:0;chr11:0-9381932:0;chr11:117147124-117147229:1;chr11:117147230-117147229:0;chr11:117147230-117147293:1;chr11:117147294-117147293:0;chr11:117147294-117147526:1;chr11:117147527-117147526:0;chr11:117147527-117147599:1;chr11:117147600-117147599:0;chr11:117147600-117148260:1;chr11:117148261-124892738:0;chr11:12354327-12362307:1;chr11:12362308-15418488:0;chr11:124892739-124897028:1;chr11:124897029-126878541:0;chr11:126878542-126879135:1;chr11:126879136-126916300:0;chr11:126916301-126929040:1;chr11:126929041-128385963:0;chr11:128385964-128388667:-1;chr11:128388668-130212881:0;chr11:130212882-130213472:1;chr11:130213473-130538031:0;chr11:130538032-130538363:1;chr11:130538364-135006516:0;chr11:15418489-15423585:1;chr11:15423586-16391702:0;chr11:16391703-16392069:1;chr11:16392070-44181815:0;chr11:44181816-44181892:1;chr11:44181893-44181892:0;chr11:44181893-44182032:1;chr11:44182033-44182032:0;chr11:44182033-44182102:1;chr11:44182103-44182102:0;chr11:44182103-44182185:1;chr11:44182186-44182185:0;chr11:44182186-44182305:1;chr11:44182306-45025344:0;chr11:45025345-45026288:1;chr11:45026289-56495916:0;chr11:56495917-56496156:1;chr11:56496157-56496156:0;chr11:56496157-56497019:1;chr11:56497020-57401772:0;chr11:57401773-57417606:1;chr11:57417607-64784205:0;chr11:64784206-64784263:1;chr11:64784264-64784263:0;chr11:64784264-64784443:1;chr11:64784444-64784443:0;chr11:64784444-64784493:1;chr11:64784494-66641858:0;chr11:66641859-66646647:1;chr11:66646648-68441694:0;chr11:68441695-68441948:1;chr11:68441949-68441948:0;chr11:68441949-68442034:1;chr11:68442035-68803684:0;chr11:68803685-69625651:1;chr11:69625652-69625651:0;chr11:69625652-69625909:1;chr11:69625910-73868933:0;chr11:73868934-73869921:1;chr11:73869922-75448865:0;chr11:75448866-75459377:1;chr11:75459378-75694533:0;chr11:75694534-75694846:1;chr11:75694847-75694846:0;chr11:75694847-75694948:1;chr11:75694949-75694948:0;chr11:75694949-75695031:1;chr11:75695032-75695031:0;chr11:75695032-75695167:1;chr11:75695168-75695167:0;chr11:75695168-75695300:1;chr11:75695301-75695300:0;chr11:75695301-75695358:1;chr11:75695359-76368659:0;chr11:76368660-76637659:1;chr11:76637660-77549723:0;chr11:77549724-77563766:1;chr11:77563767-85374187:0;chr11:85374188-85421163:1;chr11:85421164-117147123:0;chr11:9381933-9382228:1;chr11:9382229-9382228:0;chr11:9382229-9382400:-1;chr11:9382401-12354326:0;chr12:0-45141200:0;chr12:108708115-108717873:1;chr12:108717874-113323370:0;chr12:113323371-113503543:1;chr12:113503544-118963800:0;chr12:118963801-119034600:1;chr12:119034601-119035200:0;chr12:119035201-119083417:1;chr12:119083418-119654924:0;chr12:119654925-119662873:1;chr12:119662874-120405746:0;chr12:120405747-120549727:1;chr12:120549728-126054474:0;chr12:126054475-126223551:1;chr12:126223552-127222411:0;chr12:127222412-127338633:1;chr12:127338634-130372721:0;chr12:130372722-130437775:1;chr12:130437776-130437775:0;chr12:130437776-130493366:1;chr12:130493367-131752277:0;chr12:131752278-131782900:1;chr12:131782901-133851895:0;chr12:45141201-45147518:1;chr12:45147519-76829559:0;chr12:76829560-76992418:1;chr12:76992419-83849732:0;chr12:83849733-83929456:1;chr12:83929457-83929456:0;chr12:83929457-84078000:-1;chr12:84078001-84078400:0;chr12:84078401-84078700:1;chr12:84078701-86339044:0;chr12:86339045-86554000:1;chr12:86554001-86554000:0;chr12:86554001-86612079:-1;chr12:86612080-89082652:0;chr12:89082653-89116200:1;chr12:89116201-97937921:0;chr12:97937922-97972400:1;chr12:97972401-108708114:0;chr13:0-19344100:0;chr13:115109801-115169878:0;chr13:19344101-95179510:-1;chr13:95179511-95181927:0;chr13:95181928-115109800:-1;chr14:0-19964300:0;chr14:107289501-107349540:0;chr14:19964301-22470700:-1;chr14:22470701-22470700:0;chr14:22470701-22964200:-1;chr14:22964201-22964300:0;chr14:22964301-67872582:-1;chr14:67872583-67872582:0;chr14:67872583-67872847:1;chr14:67872848-67872847:0;chr14:67872848-67873011:1;chr14:67873012-67876556:0;chr14:67876557-74378955:-1;chr14:74378956-74382777:0;chr14:74382778-107289500:-1;chr15:0-35025841:0;chr15:35025842-35028678:1;chr15:35028679-48982996:0;chr15:48982997-48985588:1;chr15:48985589-102531392:0;chr16:0-4713600:0;chr16:34195701-35261153:-1;chr16:35261154-50939904:0;chr16:4713601-4716997:1;chr16:4716998-34195700:0;chr16:50939905-55068138:-1;chr16:55068139-55068138:0;chr16:55068139-55068219:1;chr16:55068220-55068219:0;chr16:55068220-55068526:1;chr16:55068527-55068526:0;chr16:55068527-55068604:1;chr16:55068605-55068604:0;chr16:55068605-55068661:1;chr16:55068662-55068661:0;chr16:55068662-55068962:1;chr16:55068963-55068962:0;chr16:55068963-55069142:1;chr16:55069143-55069142:0;chr16:55069143-55069368:1;chr16:55069369-55069368:0;chr16:55069369-70881800:-1;chr16:70881801-70881800:0;chr16:70881801-71202500:-1;chr16:71202501-71202500:0;chr16:71202501-90292700:-1;chr16:90292701-90354753:0;chr17:0-0:0;chr17:1-8533822:-1;chr17:11196743-11198407:-1;chr17:11198408-13432843:0;chr17:13432844-13433812:-1;chr17:13433813-81195210:0;chr17:8533823-8533822:0;chr17:8533823-8535644:-1;chr17:8535645-8535644:0;chr17:8535645-8537025:-1;chr17:8537026-8593733:0;chr17:8593734-8600104:-1;chr17:8600105-11196742:0;chr18:0-10000:0;chr18:10001-5916245:-1;chr18:21797646-21799799:0;chr18:21799800-78017200:-1;chr18:5916246-5916245:0;chr18:5916246-5916251:1;chr18:5916252-5916251:0;chr18:5916252-5916358:1;chr18:5916359-5916358:0;chr18:5916359-5916713:1;chr18:5916714-5916713:0;chr18:5916714-5916899:1;chr18:5916900-5916899:0;chr18:5916900-5917239:1;chr18:5917240-21797645:-1;chr18:5917240-5917239:0;chr18:78017201-78077248:0;chr19:0-59128983:0;chr1:0-21300008:0;chr1:145291801-210458588:1;chr1:210458589-210458588:0;chr1:210458589-210459644:1;chr1:210459645-210459644:0;chr1:210459645-249240500:1;chr1:21300009-21303067:1;chr1:21303068-65158405:0;chr1:249240501-249250621:0;chr1:65158406-65159600:1;chr1:65159601-81551078:0;chr1:81551079-81553406:1;chr1:81553407-145291800:0;chr20:0-63025520:0;chr21:0-10697900:0;chr21:10697901-48119800:-1;chr21:48119801-48129895:0;chr22:0-51304566:0;chr2:0-4554170:0;chr2:104041901-104095500:1;chr2:104095501-191327141:0;chr2:191327142-191327476:1;chr2:191327477-243199373:0;chr2:22229072-22234330:1;chr2:22234331-81269697:0;chr2:4554171-4554430:1;chr2:4554431-8949547:0;chr2:81269698-81269923:1;chr2:81269924-104041900:0;chr2:8949548-8949728:1;chr2:8949729-22229071:0;chr3:0-39147853:0;chr3:112017601-112019548:1;chr3:112019549-154270701:0;chr3:154270702-154271736:1;chr3:154271737-154272722:0;chr3:154272723-154273844:1;chr3:154273845-159785980:0;chr3:159785981-159786354:1;chr3:159786355-198022430:0;chr3:39147854-39148355:1;chr3:39148356-39867997:0;chr3:39867998-39870701:1;chr3:39870702-58690223:0;chr3:58690224-58691132:1;chr3:58691133-81921854:0;chr3:81921855-81922066:1;chr3:81922067-81922066:0;chr3:81922067-81923275:1;chr3:81923276-81923275:0;chr3:81923276-81924069:1;chr3:81924070-82605995:0;chr3:82605996-82606416:1;chr3:82606417-82606416:0;chr3:82606417-82606640:1;chr3:82606641-82606640:0;chr3:82606641-82606689:1;chr3:82606690-82606689:0;chr3:82606690-82606986:1;chr3:82606987-82606986:0;chr3:82606987-82607118:1;chr3:82607119-82607118:0;chr3:82607119-82607222:1;chr3:82607223-82607222:0;chr3:82607223-82607349:1;chr3:82607350-82607349:0;chr3:82607350-82607425:1;chr3:82607426-112017600:0;chr4:0-33584698:0;chr4:121063741-121064045:1;chr4:121064046-121193360:0;chr4:121193361-121201099:1;chr4:121201100-121202300:0;chr4:121202301-121204789:1;chr4:121204790-121376211:0;chr4:121376212-121378919:1;chr4:121378920-121378919:0;chr4:121378920-121379751:1;chr4:121379752-121379751:0;chr4:121379752-121380335:1;chr4:121380336-121384773:0;chr4:121384774-121385100:1;chr4:121385101-121392211:0;chr4:121392212-121394824:1;chr4:121394825-121394824:0;chr4:121394825-121403706:1;chr4:121403707-121411529:0;chr4:121411530-121412931:1;chr4:121412932-121412931:0;chr4:121412932-121413295:1;chr4:121413296-121417135:0;chr4:121417136-121417194:1;chr4:121417195-121417194:0;chr4:121417195-121417357:1;chr4:121417358-121417357:0;chr4:121417358-121417546:1;chr4:121417547-121417546:0;chr4:121417547-121417564:1;chr4:121417565-121417564:0;chr4:121417565-121417686:1;chr4:121417687-121417686:0;chr4:121417687-121417759:1;chr4:121417760-121417759:0;chr4:121417760-121417904:1;chr4:121417905-121417904:0;chr4:121417905-121417975:1;chr4:121417976-121419210:0;chr4:121419211-121427183:1;chr4:121427184-121435742:0;chr4:121435743-121451500:1;chr4:121451501-121462106:0;chr4:121462107-121462217:1;chr4:121462218-121462217:0;chr4:121462218-121462271:1;chr4:121462272-121462271:0;chr4:121462272-121462400:1;chr4:121462401-121462400:0;chr4:121462401-121462475:1;chr4:121462476-121462475:0;chr4:121462476-121462925:1;chr4:121462926-121462925:0;chr4:121462926-121463226:1;chr4:121463227-121463226:0;chr4:121463227-121463336:1;chr4:121463337-121463336:0;chr4:121463337-121463389:1;chr4:121463390-121463389:0;chr4:121463390-121463645:1;chr4:121463646-121464871:0;chr4:121464872-121465596:1;chr4:121465597-121820011:0;chr4:121820012-121824441:1;chr4:121824442-121836013:0;chr4:121836014-121837886:1;chr4:121837887-191154276:0;chr4:33584699-33586169:1;chr4:33586170-74024051:0;chr4:74024052-74024400:1;chr4:74024401-74024400:0;chr4:74024401-74025935:1;chr4:74025936-121063740:0;chr5:0-11700:0;chr5:11701-19229635:-1;chr5:155921303-155921302:0;chr5:155921303-156148060:1;chr5:156148061-156148060:0;chr5:156148061-161262793:-1;chr5:161262794-161262793:0;chr5:161262794-161323193:1;chr5:161323194-161323193:0;chr5:161323194-161803438:-1;chr5:161803439-161803438:0;chr5:161803439-161812394:1;chr5:161812395-161812394:0;chr5:161812395-180785400:-1;chr5:180785401-180915260:0;chr5:19229636-19229635:0;chr5:19229636-19230825:1;chr5:19230826-19230825:0;chr5:19230826-19234014:1;chr5:19234015-19234014:0;chr5:19234015-35802668:-1;chr5:35802669-35802668:0;chr5:35802669-36069127:1;chr5:36069128-155921302:-1;chr5:36069128-36069127:0;chr6:0-44476852:0;chr6:171050901-171115067:0;chr6:44476853-44478085:1;chr6:44478086-61880200:0;chr6:61880201-67942316:-1;chr6:67942317-67942316:0;chr6:67942317-67944773:1;chr6:67944774-171050900:-1;chr6:67944774-67944773:0;chr7:0-8593319:0;chr7:104581025-104614029:1;chr7:104614030-104963936:0;chr7:104963937-104980204:1;chr7:104980205-105156556:0;chr7:105156557-105275968:1;chr7:105275969-108286474:0;chr7:108286475-108760810:1;chr7:108760811-115712006:0;chr7:115712007-115990719:1;chr7:115990720-116261523:0;chr7:116261524-116460791:1;chr7:116460792-117602170:0;chr7:117602171-117791373:1;chr7:117791374-120190240:0;chr7:120190241-120470440:1;chr7:120470441-134117823:0;chr7:134117824-134119172:1;chr7:134119173-147390952:0;chr7:147390953-147547077:-1;chr7:147547078-159138663:0;chr7:66369592-66376603:1;chr7:66376604-78571536:0;chr7:78571537-78841883:1;chr7:78841884-83298327:0;chr7:83298328-83309528:1;chr7:83309529-91502782:0;chr7:8593320-8595330:1;chr7:8595331-66369591:0;chr7:91502783-91823445:1;chr7:91823446-91823445:0;chr7:91823446-91862000:1;chr7:91862001-91862059:0;chr7:91862060-92251533:1;chr7:92251534-93188023:0;chr7:93188024-93188254:1;chr7:93188255-94397927:0;chr7:94397928-94536780:1;chr7:94536781-94536780:0;chr7:94536781-94536854:-1;chr7:94536855-94766700:0;chr7:94766701-94955797:1;chr7:94955798-99486900:0;chr7:99486901-99620485:1;chr7:99620486-104581024:0;chr8:0-53161600:0;chr8:104115596-104115699:1;chr8:104115700-104115699:0;chr8:104115700-104116026:1;chr8:104116027-104116026:0;chr8:104116027-104116083:1;chr8:104116084-104116083:0;chr8:104116084-104116285:1;chr8:104116286-146364022:0;chr8:53161601-53162633:1;chr8:53162634-104115595:0;chr9:0-31826826:0;chr9:31826827-31826915:1;chr9:31826916-31826915:0;chr9:31826916-31827116:1;chr9:31827117-31827116:0;chr9:31827117-31827190:1;chr9:31827191-31827190:0;chr9:31827191-31827336:1;chr9:31827337-31827336:0;chr9:31827337-31827379:1;chr9:31827380-31827379:0;chr9:31827380-31827515:1;chr9:31827516-31827515:0;chr9:31827516-31827619:1;chr9:31827620-31827619:0;chr9:31827620-31827676:1;chr9:31827677-31827676:0;chr9:31827677-31827754:1;chr9:31827755-31827754:0;chr9:31827755-31827990:1;chr9:31827991-31827990:0;chr9:31827991-31828126:1;chr9:31828127-31828126:0;chr9:31828127-31828193:1;chr9:31828194-31828193:0;chr9:31828194-31828279:1;chr9:31828280-31828279:0;chr9:31828280-31828357:1;chr9:31828358-36641818:0;chr9:36641819-36643600:1;chr9:36643601-75292968:0;chr9:75292969-75296243:1;chr9:75296244-84607000:0;chr9:84607001-84608900:1;chr9:84608901-87600731:0;chr9:87600732-87603266:1;chr9:87603267-141213431:0;chrX:0-37987927:0;chrX:106904719-106907002:1;chrX:106907003-123523856:0;chrX:123523857-123527127:1;chrX:123527128-155270560:0;chrX:37987928-37987956:1;chrX:37987957-37987956:0;chrX:37987957-37988417:1;chrX:37988418-37988417:0;chrX:37988418-37988711:1;chrX:37988712-54596066:0;chrX:54596067-54602748:1;chrX:54602749-106904718:0;chrY:0-2649500:0;chrY:2649501-59020600:-1;chrY:59020601-59373566:0 hs1:165293730-165293730,hs4:121417863-121417863;hs1:210458589-210458589,hs15:35025842-35025842;hs1:21303068-21303068,hs5:3117025-3117025;hs1:65159601-65159601,hsX:106904719-106904719;hs1:81553407-81553407,hs3:39148356-39148356;hs2:8949729-8949729,hs9:75292969-75292969;hs2:191327142-191327142,hs10:113717969-113717969;hs2:22234331-22234331,hs9:84608956-84608956;hs2:191327142-191327142,hs10:113717960-113717960;hs2:8949729-8949729,hs9:75292969-75292969;hs2:4554431-4554431,hsX:37988712-37988712;hs3:39870702-39870702,hs21:16344797-16344797;hs3:58691133-58691133,hs15:48982997-48982997;hs3:82605996-82605996,hs16:55068139-55068139;hs3:82606143-82606143,hs4:121417461-121417461;hs3:82605998-82605998,hs16:55068139-55068139;hs3:112017551-112017551,hs1:81551079-81551079;hs3:39870702-39870702,hs21:16344797-16344797;hs3:39870702-39870702,hs21:16344797-16344797;hs3:154271737-154271737,hsX:123527128-123527128;hs3:154273845-154273845,hs4:121064046-121064046;hs3:52429273-52429273,hs16:55068250-55068250;hs3:81924070-81924070,hs3:82607426-82607426;hs3:112019549-112019549,hs7:134117824-134117824;hs3:75370216-75370216,hs4:33584699-33584699;hs3:39870702-39870702,hs21:16344797-16344797;hs3:82605997-82605997,hs16:55068139-55068139;hs4:121417378-121417378,hs8:104116163-104116163;hs4:121417654-121417654,hs3:159785981-159785981;hs4:121417936-121417936,hs3:81921856-81921856;hs4:121824442-121824442,hs3:39867998-39867998;hs4:121411530-121411530,hs11:56496157-56496157;hs4:121378948-121378948,hs8:83933060-83933060;hs4:121376212-121376212,hs3:154272723-154272723;hs4:121824442-121824442,hs3:39867998-39867998;hs4:121380423-121380423,hs17:8533823-8533823;hs4:121464872-121464872,hs12:119654925-119654925;hs4:121824442-121824442,hs3:39867998-39867998;hs4:121824442-121824442,hs3:39867998-39867998;hs4:121417976-121417976,hs18:5916501-5916501;hs4:121824442-121824442,hs3:39867998-39867998;hs4:121417936-121417936,hs3:81921855-81921855;hs4:121193361-121193361,hs2:4554171-4554171;hs4:121419211-121419211,hs4:121392212-121392212;hs4:74025936-74025936,hs11:130212882-130212882;hs4:121413296-121413296,hs14:67872583-67872583;hs4:121463337-121463337,hs9:31828280-31828280;hs4:121417905-121417905,hs8:104115700-104115700;hs4:121837887-121837887,hs6:44478086-44478086;hs4:121201100-121201100,hs1:15188275-15188275;hs4:121824442-121824442,hs3:39867998-39867998;hs4:121417264-121417264,hs16:55068230-55068230;hs5:156148061-156148061,hs7:104963937-104963937;hs5:161812395-161812395,hs7:108760811-108760811;hs5:161262794-161262794,hs12:113323371-113323371;hs5:156148061-156148061,hs7:104963937-104963937;hs5:156148061-156148061,hs7:104963937-104963937;hs5:156148061-156148061,hs7:104963937-104963937;hs5:161323194-161323194,hs7:66369592-66369592;hs5:156148061-156148061,hs7:104963937-104963937;hs5:156148061-156148061,hs7:104963937-104963937;hs6:67942318-67942318,hs18:21797646-21797646;hs6:67942317-67942317,hs18:21797646-21797646;hs6:67944774-67944774,hs4:121063741-121063741;hs7:115990720-115990720,hs5:161803439-161803439;hs7:78841884-78841884,hs7:104980205-104980205;hs7:78571539-78571539,hs12:127222412-127222412;hs7:103510446-103510446,hs7:77880721-77880721;hs7:78841884-78841884,hs7:104980205-104980205;hs7:94536781-94536781,hs12:113503543-113503543;hs7:78841884-78841884,hs7:104980205-104980205;hs7:121627499-121627499,hs12:102179993-102179993;hs7:77911463-77911463,hs12:95094232-95094232;hs7:83298328-83298328,hs12:97937922-97937922;hs7:78571537-78571537,hs12:127222412-127222412;hs7:103510446-103510446,hs7:77880721-77880721;hs7:8595331-8595331,hs4:121820012-121820012;hs7:78841884-78841884,hs7:104980205-104980205;hs7:8595331-8595331,hs4:121820012-121820012;hs7:78841884-78841884,hs7:104980205-104980205;hs7:110802400-110802400,hs12:81954975-81954975;hs7:81714849-81714849,hs12:115899265-115899265;hs7:120190241-120190241,hs7:116261524-116261524;hs7:120470444-120470444,hs12:126054475-126054475;hs7:120470441-120470441,hs12:126054475-126054475;hs7:8595331-8595331,hs4:121820012-121820012;hs7:78571539-78571539,hs12:127222412-127222412;hs7:121627499-121627499,hs12:102179993-102179993;hs7:78841884-78841884,hs7:104980205-104980205;hs7:99620486-99620486,hs12:130437776-130437776;hs7:83309529-83309529,hs12:131789493-131789493;hs7:78571539-78571539,hs12:127222412-127222412;hs7:110802400-110802400,hs12:81954975-81954975;hs7:8595331-8595331,hs4:121820012-121820012;hs7:78841884-78841884,hs7:104980205-104980205;hs7:110802400-110802400,hs12:81954975-81954975;hs7:121627499-121627499,hs12:102179993-102179993;hs7:115712007-115712007,hs7:105156557-105156557;hs7:103510446-103510446,hs7:77880721-77880721;hs7:83544640-83544640,hs12:114331707-114331707;hs7:103510446-103510446,hs7:77880721-77880721;hs7:78571539-78571539,hs12:127222412-127222412;hs7:110802400-110802400,hs12:81954975-81954975;hs7:120470444-120470444,hs12:126054475-126054475;hs7:104614030-104614030,hs12:120405747-120405747;hs7:117602171-117602171,hs12:83849733-83849733;hs7:78841884-78841884,hs7:104980205-104980205;hs7:104581025-104581025,hs5:35802669-35802669;hs7:78571539-78571539,hs12:127222412-127222412;hs7:8595331-8595331,hs4:121820012-121820012;hs7:78571539-78571539,hs12:127222412-127222412;hs7:134119173-134119173,hsX:106907003-106907003;hs7:78571539-78571539,hs12:127222412-127222412;hs7:78841884-78841884,hs7:104980205-104980205;hs7:69495001-69495001,hs7:108322294-108322294;hs7:110802400-110802400,hs12:81954975-81954975;hs8:104116104-104116104,hs4:121417286-121417286;hs9:75296244-75296244,hs5:19229636-19229636;hs9:31826827-31826827,hs8:83932475-83932475;hs9:87603267-87603267,hs19:36097318-36097318;hs9:31827044-31827044,hs19:4796792-4796792;hs9:84606754-84606754,hs13:91243171-91243171;hs9:31828358-31828358,hs4:121462218-121462218;hs9:31827765-31827765,hs8:104116067-104116067;hs9:31828358-31828358,hs18:5916246-5916246;hs9:87603267-87603267,hs19:36097315-36097315;hs9:31828358-31828358,hs18:5916254-5916254;hs9:31828194-31828194,hs16:55068573-55068573;hs9:31828357-31828357,hs18:5916252-5916252;hs9:31827191-31827191,hs3:39147854-39147854;hs9:87600732-87600732,hs1:62111132-62111132;hs9:31828358-31828358,hs18:5916252-5916252;hs10:113718857-113718857,hs17:8535645-8535645;hs10:591340-591340,hs2:191327477-191327477;hs11:1326028-1326028,hs11:31653815-31653815;hs11:76637660-76637660,hs11:124897029-124897029;hs11:57417607-57417607,hs11:66646648-66646648;hs11:9919595-9919595,hs11:85426706-85426706;hs11:9919595-9919595,hs11:85426706-85426706;hs11:76637660-76637660,hs11:124897029-124897029;hs11:76637660-76637660,hs11:124897029-124897029;hs11:77563767-77563767,hs11:117148261-117148261;hs11:130213473-130213473,hs3:58690224-58690224;hs11:77563767-77563767,hs11:117148261-117148261;hs11:45026289-45026289,hsX:68397023-68397023;hs11:76637660-76637660,hs11:124897029-124897029;hs11:76637660-76637660,hs11:124897029-124897029;hs11:76637660-76637660,hs11:124897029-124897029;hs11:77563767-77563767,hs11:117148261-117148261;hs11:126878542-126878542,hs11:66823707-66823707;hs11:76637660-76637660,hs11:124897029-124897029;hs11:76368660-76368660,hs11:68803685-68803685;hs11:126879136-126879136,hs3:154270702-154270702;hs11:76637660-76637660,hs11:124897029-124897029;hs11:76637660-76637660,hs11:124897029-124897029;hs11:132369393-132369393,hs11:132512590-132512590;hs12:92615064-92615064,hs7:103608418-103608418;hs12:113503544-113503544,hs7:94536781-94536781;hs12:120549728-120549728,hs12:127338634-127338634;hs12:84079046-84079046,hs7:91823446-91823446;hs12:108717874-108717874,hs7:92251534-92251534;hs12:86619375-86619375,hs7:118627961-118627961;hs12:85017567-85017567,hs7:122681826-122681826;hs12:131752278-131752278,hs12:108708115-108708115;hs12:115951726-115951726,hs7:99998981-99998981;hs12:130493367-130493367,hs7:72049139-72049139;hs12:108717874-108717874,hs7:92251534-92251534;hs12:80918589-80918589,hs7:118705273-118705273;hs12:117588280-117588280,hs7:84517474-84517474;hs12:85010634-85010634,hs12:84958329-84958329;hs12:71583198-71583198,hs7:122785001-122785001;hs12:126223552-126223552,hs7:116460792-116460792;hs12:86553951-86553951,hs12:97972401-97972401;hs12:114420349-114420349,hs7:91862060-91862060;hs12:84979149-84979149,hs7:44408103-44408103;hs12:86339045-86339045,hs12:76829560-76829560;hs12:83929457-83929457,hs7:94955798-94955798;hs12:92536461-92536461,hs12:83241931-83241931;hs13:95181928-95181928,hs16:4716998-4716998;hs13:91248182-91248182,hs4:121378920-121378920;hs14:67873054-67873054,hs4:121417135-121417135;hs14:67873054-67873054,hs4:121417134-121417134;hs14:67876557-67876557,hs16:70177697-70177697;hs15:35028679-35028679,hs14:74378956-74378956;hs15:48985589-48985589,hs4:121202127-121202127;hs15:35028678-35028678,hs14:74378956-74378956;hs15:48985589-48985589,hs4:121202126-121202126;hs16:55069143-55069143,hs9:31827380-31827380;hs16:55068360-55068360,hs4:74024401-74024401;hs16:55068141-55068141,hs3:82605998-82605998;hs16:55068522-55068522,hs4:121463136-121463136;hs16:55068590-55068590,hs9:31827671-31827671;hs16:55069351-55069351,hs17:67989864-67989864;hs16:55068613-55068613,hs4:121417195-121417195;hs16:55068320-55068320,hs4:121417132-121417132;hs16:55068605-55068605,hs3:52429256-52429256;hs16:55068141-55068141,hs3:82605996-82605996;hs16:55069369-55069369,hs6:44476853-44476853;hs16:46854568-46854568,hs16:35261154-35261154;hs17:11196743-11196743,hs11:56495891-56495891;hs17:8537026-8537026,hs19:40892008-40892008;hs17:11196743-11196743,hs11:56495891-56495891;hs17:41026033-41026033,hs13:95179511-95179511;hs17:67990162-67990162,hs16:55068156-55068156;hs17:13432844-13432844,hs9:36643722-36643722;hs18:5916714-5916714,hs11:56495917-56495917;hs18:21799800-21799800,hs4:121398342-121398342;hs18:5917240-5917240,hs9:31827074-31827074;hs18:5916359-5916359,hs16:55068220-55068220;hs19:40892008-40892008,hs17:8537025-8537025;hs21:38837704-38837704,hs11:56497020-56497020;hs21:38837704-38837704,hs11:56497020-56497020;hs21:38837704-38837704,hs11:56497020-56497020;hsX:54596067-54596067,hs16:4713550-4713550;hsX:78097227-78097227,hs8:104115715-104115715;hsX:123523857-123523857,hs2:22229072-22229072;hsX:54602749-54602749,hs1:21300009-21300009;hsX:123527128-123527128,hs3:154271735-154271735 ACER3;ARL2;ARL2-SNX15;BAGE3;BAGE4;C11orf67;C1orf74;C2CD3;CCDC15;CCDC89;CCND1;CREBZF;ELP4;ETS1;EXT2;FGF19;FGF3;FGF4;LOC100507206;LOC283104;LOC387895;LOC388276;LOC646627;LRRC32;MICALCL;MYEOV;OPCML;ORAOV1;PC;RNF214;SBF2;SOX6;SYTL2;TOLLIP;TPCN2;TSKU;UVRAG;YPEL4; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes ACER3,RNF214;ACER3,SBF2;ACER3,UVRAG;ARL2-SNX15,CCDC15;ARL2,CCDC15;C11orf67,CCDC15;ELP4,TOLLIP;EXT2,CCDC15;EXT2,RNF214;EXT2,UVRAG;NRXN2,C2CD3 CTDB0396 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 1 Glioma Next Generation Sequencing Homo sapiens SJHGG052_A Illumina Genome Analyzer IIx or HiSeq chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-88770568:0;chr16:88770569-88775128:-1;chr16:88775129-90354753:0;chr17:0-0:0;chr17:1-53752100:-1;chr17:53752101-81195210:0;chr18:0-4799362:0;chr18:4799363-4800722:1;chr18:4800723-78077248:0;chr19:0-59128983:0;chr1:0-160184572:0;chr1:160184573-160250709:1;chr1:160250710-164413579:0;chr1:164413580-164942182:1;chr1:164942183-179645200:0;chr1:179645201-179672902:1;chr1:179672903-189845500:0;chr1:189845501-190084826:1;chr1:190084827-191539361:0;chr1:191539362-191840800:1;chr1:191840801-213590917:0;chr1:213590918-213806500:1;chr1:213806501-213806600:0;chr1:213806601-213826652:1;chr1:213826653-213826652:0;chr1:213826653-214099100:1;chr1:214099101-215150731:0;chr1:215150732-215383700:1;chr1:215383701-215383700:0;chr1:215383701-215438700:1;chr1:215438701-217011100:0;chr1:217011101-217011649:1;chr1:217011650-223845282:0;chr1:223845283-223864287:1;chr1:223864288-224159300:0;chr1:224159301-224433800:1;chr1:224433801-226111380:0;chr1:226111381-226130723:1;chr1:226130724-226299312:0;chr1:226299313-226307700:1;chr1:226307701-231617388:0;chr1:231617389-231617502:-1;chr1:231617503-243631700:0;chr1:243631701-243666411:1;chr1:243666412-243666411:0;chr1:243666412-244255809:1;chr1:244255810-244255809:0;chr1:244255810-244258832:1;chr1:244258833-244258832:0;chr1:244258833-244456847:1;chr1:244456848-244456847:0;chr1:244456848-244483720:1;chr1:244483721-244483720:0;chr1:244483721-244613600:1;chr1:244613601-244613600:0;chr1:244613601-244639300:1;chr1:244639301-244639300:0;chr1:244639301-244775604:1;chr1:244775605-244775604:0;chr1:244775605-244791274:1;chr1:244791275-244791274:0;chr1:244791275-244810891:1;chr1:244810892-244810891:0;chr1:244810892-244824391:1;chr1:244824392-244824391:0;chr1:244824392-244912500:1;chr1:244912501-248575282:0;chr1:248575283-248841426:1;chr1:248841427-249250621:0;chr20:0-7958500:0;chr20:30504301-30504600:1;chr20:30504601-30504600:0;chr20:30504601-30875100:1;chr20:30875101-63025520:0;chr20:7958501-8357700:1;chr20:8357701-8847000:0;chr20:8847001-8848000:1;chr20:8848001-8848000:0;chr20:8848001-9430500:1;chr20:9430501-30504300:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-16271700:0;chr2:154222901-232427800:1;chr2:16271701-16273700:1;chr2:16273701-154222900:0;chr2:232427801-232427800:0;chr2:232427801-232454600:1;chr2:232454601-232454600:0;chr2:232454601-243183600:1;chr2:243183601-243199373:0;chr3:0-71141292:0;chr3:71141293-71142503:1;chr3:71142504-198022430:0;chr4:0-66028885:0;chr4:66028886-66078980:-1;chr4:66078981-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-81250209:0;chr7:81250210-81494866:-1;chr7:81494867-159138663:0;chr8:0-146364022:0;chr9:0-125778877:0;chr9:125778878-125813203:1;chr9:125813204-125858274:0;chr9:125858275-125932429:1;chr9:125932430-126014933:0;chr9:126014934-126372978:1;chr9:126372979-141213431:0;chrX:0-155270560:0;chrY:0-2649500:0;chrY:2649501-59033300:-1;chrY:59033301-59373566:0 hs1:179271743-179271743,hs1:217011514-217011514;hs1:213806462-213806462,hs1:213977967-213977967;hs1:181415623-181415623,hs2:16059652-16059652;hs1:244085168-244085168,hs2:16158764-16158764;hs1:244015023-244015023,hs2:15779022-15779022;hs1:244257689-244257689,hs2:16109043-16109043;hs1:243666412-243666412,hs1:213826653-213826653;hs1:160250710-160250710,hs2:16080516-16080516;hs1:226130724-226130724,hs2:16194175-16194175;hs1:243637600-243637600,hs2:16125188-16125188;hs1:224137797-224137797,hs2:16397105-16397105;hs1:160250710-160250710,hs2:16080516-16080516;hs1:244456848-244456848,hs1:244810892-244810892;hs1:248774822-248774822,hs2:16027731-16027731;hs1:244791275-244791275,hs1:244483721-244483721;hs1:248575283-248575283,hs1:223845283-223845283;hs1:244349557-244349557,hs2:16246164-16246164;hs1:189136623-189136623,hs1:189115741-189115741;hs1:244871886-244871886,hs1:243855104-243855104;hs2:15841330-15841330,hs2:49631766-49631766;hs2:15951349-15951349,hs2:15903825-15903825;hs2:16148785-16148785,hs2:15939326-15939326;hs2:16055176-16055176,hs9:126014934-126014934;hs2:25962331-25962331,hs2:8807104-8807104;hs2:19947861-19947861,hs2:19860821-19860821;hs2:16035150-16035150,hs1:243948145-243948145;hs2:234728796-234728796,hs2:218858882-218858882;hs2:8880748-8880748,hs2:15934069-15934069;hs2:19859431-19859431,hs2:19898110-19898110;hs2:16150007-16150007,hs1:215150732-215150732;hs2:19783472-19783472,hs2:15892291-15892291;hs2:39118884-39118884,hs2:20100857-20100857;hs2:16366647-16366647,hs2:39127050-39127050;hs2:8787891-8787891,hs2:15748741-15748741;hs2:15822080-15822080,hs2:25907992-25907992;hs2:15778713-15778713,hs2:19849548-19849548;hs2:15779268-15779268,hs2:16397698-16397698;hs2:8487264-8487264,hs2:39223318-39223318;hs3:192845451-192845451,hs4:68648092-68648092;hs8:110370886-110370886,hs2:204851878-204851878;hs9:117975339-117975339,hs11:23122707-23122707;hs11:23123086-23123086,hs9:117975343-117975343;hs13:73474991-73474991,hs13:67519164-67519164;hs22:39487230-39487230,hs10:128526501-128526501;hsX:42602326-42602326,hs6:19983013-19983013 1-Dec;ADSS;C1orf100;C1orf101;C2orf57;CAPN8;DCAF8;DEGS1;ESRRG;FAM5C;FBXO28;KCNK2;LEFTY2;NVL;OR2G6;OR2T10;OR2T11;OR2T27;OR2T29;OR2T34;OR2T35;PBX1;PEA15;PEX19;PPPDE1;PYCR2;SOAT1;TDRD5;ZNF238; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes C1orf101,PPPDE1;SOAT1,ESRRG;ZNF238,C1orf101 CTDB0397 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 4 Glioma Next Generation Sequencing Homo sapiens SJHGG075_A Illumina Genome Analyzer IIx or HiSeq chr10:0-135534747:0;chr11:0-67279338:0;chr11:67279339-67280708:1;chr11:67280709-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-60000:0;chr16:12847041-12847051:1;chr16:12847052-12847051:0;chr16:12847052-12852092:1;chr16:12852093-12852092:0;chr16:12852093-12852270:1;chr16:12852271-12852270:0;chr16:12852271-12865559:1;chr16:12865560-23725353:0;chr16:1476601-12847040:0;chr16:23725354-23725554:1;chr16:23725555-23725554:0;chr16:23725555-23725875:1;chr16:23725876-23725875:0;chr16:23725876-23726002:1;chr16:23726003-27236089:0;chr16:27236090-27236335:1;chr16:27236336-48236182:0;chr16:48236183-48236335:1;chr16:48236336-48236731:0;chr16:48236732-48236759:1;chr16:48236760-48236759:0;chr16:48236760-48237019:1;chr16:48237020-48237019:0;chr16:48237020-48237212:1;chr16:48237213-48237212:0;chr16:48237213-48237315:1;chr16:48237316-52292205:0;chr16:52292206-52292278:1;chr16:52292279-52292278:0;chr16:52292279-52292488:1;chr16:52292489-52292488:0;chr16:52292489-52292653:1;chr16:52292654-52301591:0;chr16:52301592-52301829:1;chr16:52301830-52301829:0;chr16:52301830-52302040:1;chr16:52302041-52302040:0;chr16:52302041-52302225:1;chr16:52302226-52303496:0;chr16:52303497-52304379:1;chr16:52304380-52837006:0;chr16:52837007-52837286:1;chr16:52837287-52837286:0;chr16:52837287-52837444:1;chr16:52837445-52837444:0;chr16:52837445-52837567:1;chr16:52837568-52837567:0;chr16:52837568-52837843:1;chr16:52837844-52837843:0;chr16:52837844-52837896:1;chr16:52837897-65015521:0;chr16:60001-1476600:-1;chr16:65015522-65016184:1;chr16:65016185-65016184:0;chr16:65016185-65016814:1;chr16:65016815-65016814:0;chr16:65016815-65016956:1;chr16:65016957-69969014:0;chr16:69969015-69969228:1;chr16:69969229-71010800:0;chr16:71010801-71010882:1;chr16:71010883-71010882:0;chr16:71010883-71011006:1;chr16:71011007-71011006:0;chr16:71011007-71011157:1;chr16:71011158-71011157:0;chr16:71011158-71011311:1;chr16:71011312-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-854400:0;chr1:1574301-249250621:0;chr1:854401-1574300:-1;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-54561948:0;chr4:111066306-111085094:1;chr4:111085095-114496373:0;chr4:114496374-114496630:1;chr4:114496631-114496630:0;chr4:114496631-114496790:1;chr4:114496791-114496790:0;chr4:114496791-114497040:1;chr4:114497041-114500638:0;chr4:114500639-114500709:1;chr4:114500710-114500709:0;chr4:114500710-114500941:1;chr4:114500942-114500941:0;chr4:114500942-114501140:1;chr4:114501141-114501140:0;chr4:114501141-114501220:1;chr4:114501221-114505714:0;chr4:114505715-114505802:1;chr4:114505803-114505802:0;chr4:114505803-114505952:1;chr4:114505953-115105647:0;chr4:115105648-115105821:1;chr4:115105822-115105821:0;chr4:115105822-115105913:1;chr4:115105914-115105913:0;chr4:115105914-115105992:1;chr4:115105993-115105992:0;chr4:115105993-115106200:1;chr4:115106201-135555464:0;chr4:135555465-135555730:1;chr4:135555731-157014670:0;chr4:157014671-157014847:1;chr4:157014848-157014847:0;chr4:157014848-157014853:1;chr4:157014854-157014853:0;chr4:157014854-157015417:1;chr4:157015418-157015417:0;chr4:157015418-157015648:1;chr4:157015649-157015648:0;chr4:157015649-157015689:1;chr4:157015690-157544075:0;chr4:157544076-157544318:1;chr4:157544319-167367680:0;chr4:167367681-167368117:1;chr4:167368118-167368117:0;chr4:167368118-167368238:1;chr4:167368239-167368238:0;chr4:167368239-167368475:1;chr4:167368476-167368475:0;chr4:167368476-167368722:1;chr4:167368723-191154276:0;chr4:54561949-55998274:1;chr4:55998275-86545800:0;chr4:86545801-86552058:1;chr4:86552059-111066305:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-146364022:0;chr9:0-139218400:0;chr9:139218401-140360200:-1;chr9:140360201-141213431:0;chrX:0-124406000:0;chrX:124406001-124415000:-1;chrX:124415001-155270560:0;chrY:0-59373566:0 hs1:160522842-160522842,hs2:147291273-147291273;hs2:35056944-35056944,hs20:23093718-23093718;hs2:104989746-104989746,hs8:137701896-137701896;hs4:157015690-157015690,hs16:48237211-48237211;hs4:111066306-111066306,hs16:12847050-12847050;hs4:114500710-114500710,hs16:48236760-48236760;hs4:114505953-114505953,hs16:52837568-52837568;hs4:111066306-111066306,hs16:12847050-12847050;hs4:114505953-114505953,hs16:52837572-52837572;hs4:115105822-115105822,hs4:114496744-114496744;hs4:86552059-86552059,hs4:111085095-111085095;hs4:86552059-86552059,hs4:111085095-111085095;hs4:115105914-115105914,hs4:114496405-114496405;hs4:111066306-111066306,hs16:12847050-12847050;hs4:111066306-111066306,hs16:12847050-12847050;hs4:114500710-114500710,hs16:48236760-48236760;hs4:111066306-111066306,hs16:12847050-12847050;hs4:86552059-86552059,hs4:111085095-111085095;hs4:111066306-111066306,hs16:12847050-12847050;hs4:111066306-111066306,hs16:12847050-12847050;hs4:86552059-86552059,hs4:111085095-111085095;hs4:114500710-114500710,hs16:48236760-48236760;hs4:86552059-86552059,hs4:111085095-111085095;hs4:114500710-114500710,hs16:48236760-48236760;hs4:178006250-178006250,hs4:177283845-177283845;hs4:86552059-86552059,hs4:111085095-111085095;hs4:111066307-111066307,hs16:12847050-12847050;hs4:111066306-111066306,hs16:12847050-12847050;hs4:114501141-114501141,hs16:52837287-52837287;hs4:114500710-114500710,hs16:48236760-48236760;hs6:94179585-94179585,hs9:100907845-100907845;hs6:71020488-71020488,hs9:5586122-5586122;hs8:137701896-137701896,hs5:5695845-5695845;hs9:28911555-28911555,hs6:94179602-94179602;hs15:57861466-57861466,hs15:97800496-97800496;hs15:79594850-79594850,hs2:235864474-235864474;hs16:48236336-48236336,hs16:48237316-48237316;hs16:65016734-65016734,hs4:114496791-114496791;hs16:12852271-12852271,hs16:12865560-12865560;hs16:65016738-65016738,hs4:114496791-114496791;hs16:71011340-71011340,hs4:114500750-114500750;hs16:71011340-71011340,hs4:114500754-114500754;hs16:52837897-52837897,hs4:115105648-115105648;hs16:48237171-48237171,hs4:114505803-114505803;hs16:65016815-65016815,hs4:114496374-114496374;hs16:48237213-48237213,hs4:157015690-157015690;hs16:48236336-48236336,hs16:48237316-48237316;hs16:23725964-23725964,hs4:135555725-135555725;hs16:12852271-12852271,hs16:12865560-12865560;hs16:12847052-12847052,hs4:111066306-111066306;hs16:12852271-12852271,hs16:12865560-12865560;hs16:48237171-48237171,hs4:114505807-114505807;hs16:48237167-48237167,hs4:157544070-157544070;hs16:12852271-12852271,hs16:12865560-12865560;hs16:48236336-48236336,hs16:48237316-48237316;hs16:48237167-48237167,hs4:157544077-157544077;hs16:52304380-52304380,hs4:157014854-157014854;hs16:48237167-48237167,hs4:157544076-157544076;hs16:48237171-48237171,hs4:114505803-114505803;hs16:12852271-12852271,hs16:12865560-12865560;hs16:52304380-52304380,hs4:157014853-157014853;hs16:12852271-12852271,hs16:12865560-12865560;hs16:48237171-48237171,hs4:114505715-114505715;hs16:69969141-69969141,hs4:167368339-167368339;hs16:48237171-48237171,hs4:114505715-114505715;hs16:65016813-65016813,hs4:114496374-114496374;hs20:23093720-23093720,hs2:35056942-35056942 ARHGAP24;C16orf91;CAMK2D;CHIC2;ELOVL6;GSX2;KDR;KIT;LOC643988;PDGFRA; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes ARHGAP24,CPPED1;ARHGAP24,ELOVL6;ARHGAP24,VKORC1;CAMK2D,ABCC11;CAMK2D,CDH11;ELOVL6,CPPED1;ELOVL6,VKORC1 CTDB0398 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 4 Glioma Next Generation Sequencing Homo sapiens SJHGG078_A Illumina Genome Analyzer IIx or HiSeq chr10:0-135534747:0;chr11:0-133700:0;chr11:133701-134946400:-1;chr11:134946401-135006516:0;chr12:0-61100808:0;chr12:61100809-63227800:1;chr12:63227801-133851895:0;chr13:0-19342700:0;chr13:115109801-115169878:0;chr13:19342701-115109800:-1;chr14:0-100592200:0;chr14:100592201-100618100:-1;chr14:100618101-107349540:0;chr15:0-35887171:0;chr15:102465301-102531392:0;chr15:35887172-102465300:-1;chr16:0-57785000:0;chr16:57785001-57796800:-1;chr16:57796801-90354753:0;chr17:0-43492468:0;chr17:43492469-44614500:-1;chr17:44614501-44784400:0;chr17:44784401-45190532:1;chr17:45190533-45802700:0;chr17:45802701-53820186:-1;chr17:53820187-56033153:0;chr17:56033154-56183000:1;chr17:56183001-60848698:0;chr17:60848699-60866100:1;chr17:60866101-61539704:0;chr17:61539705-61539800:-1;chr17:61539801-61956637:0;chr17:61956638-61957600:-1;chr17:61957601-64898206:0;chr17:64898207-64899770:1;chr17:64899771-64899770:0;chr17:64899771-65679865:-1;chr17:65679866-65679865:0;chr17:65679866-65682245:1;chr17:65682246-75728608:0;chr17:75728609-78788900:1;chr17:78788901-80024000:0;chr17:80024001-80035200:1;chr17:80035201-81195210:0;chr18:0-31148627:0;chr18:31148628-48955511:1;chr18:48955512-49331767:0;chr18:49331768-78017200:-1;chr18:78017201-78077248:0;chr19:0-27749500:0;chr19:27749501-37280400:1;chr19:37280401-37280700:0;chr19:37280701-37281404:1;chr19:37281405-37281404:0;chr19:37281405-39234196:1;chr19:39234197-59128983:0;chr1:0-1987458:0;chr1:10029101-10029100:0;chr1:10029101-10482526:1;chr1:10482527-10482526:0;chr1:10482527-10483826:1;chr1:10483827-10483826:0;chr1:10483827-10607700:1;chr1:10607701-10607700:0;chr1:10607701-10684300:1;chr1:10684301-10684300:0;chr1:10684301-10827377:1;chr1:10827378-10827377:0;chr1:10827378-16050700:1;chr1:16050701-16086100:0;chr1:16086101-19816707:1;chr1:190426701-190443500:0;chr1:190443501-249240500:1;chr1:19816708-19816707:0;chr1:19816708-20053571:1;chr1:1987459-2023600:1;chr1:20053572-20053571:0;chr1:20053572-22993320:1;chr1:2023601-2996920:0;chr1:22993321-22993320:0;chr1:22993321-23249676:1;chr1:23249677-23249676:0;chr1:23249677-25563489:1;chr1:249240501-249250621:0;chr1:25563490-25563489:0;chr1:25563490-26301900:1;chr1:26301901-26301900:0;chr1:26301901-26334200:1;chr1:26334201-26334200:0;chr1:26334201-26663700:1;chr1:26663701-26663700:0;chr1:26663701-26727900:1;chr1:26727901-26727900:0;chr1:26727901-26963900:1;chr1:26963901-26964000:0;chr1:26964001-27330886:1;chr1:27330887-27330886:0;chr1:27330887-27655000:1;chr1:27655001-27696900:0;chr1:27696901-32192300:1;chr1:2996921-3238100:1;chr1:32192301-32239100:0;chr1:32239101-32705000:1;chr1:3238101-3349155:0;chr1:32705001-32720300:0;chr1:32720301-35581089:1;chr1:3349156-3349529:1;chr1:3349530-3349529:0;chr1:3349530-3368600:1;chr1:3368601-3651900:0;chr1:35581090-35581089:0;chr1:35581090-36022700:1;chr1:36022701-36022700:0;chr1:36022701-39393588:1;chr1:3651901-10029100:1;chr1:39393589-39393588:0;chr1:39393589-44228900:1;chr1:44228901-44228900:0;chr1:44228901-46176700:1;chr1:46176701-46176700:0;chr1:46176701-48073400:1;chr1:48073401-48073400:0;chr1:48073401-53975900:1;chr1:53975901-53975900:0;chr1:53975901-54694200:1;chr1:54694201-54694200:0;chr1:54694201-60748633:1;chr1:60748634-60748633:0;chr1:60748634-61794205:1;chr1:61794206-61794205:0;chr1:61794206-65187600:1;chr1:65187601-65187600:0;chr1:65187601-65616730:1;chr1:65616731-65616730:0;chr1:65616731-65618998:1;chr1:65618999-65618998:0;chr1:65618999-67223852:1;chr1:67223853-190426700:1;chr1:67223853-67223852:0;chr20:0-62343400:0;chr20:62343401-62364600:1;chr20:62364601-63025520:0;chr21:0-15677700:0;chr21:15677701-15694812:1;chr21:15694813-15694812:0;chr21:15694813-15705361:1;chr21:15705362-15763600:0;chr21:15763601-15821087:-1;chr21:15821088-15823978:0;chr21:15823979-16399607:-1;chr21:16399608-16686724:0;chr21:16686725-16703045:1;chr21:16703046-16703045:0;chr21:16703046-16703662:1;chr21:16703663-17684365:0;chr21:17684366-17830369:1;chr21:17830370-18505967:0;chr21:18505968-18507222:1;chr21:18507223-18507222:0;chr21:18507223-18507625:1;chr21:18507626-18507625:0;chr21:18507626-18523600:1;chr21:18523601-18814922:0;chr21:18814923-18944640:-1;chr21:18944641-20011003:0;chr21:20011004-20015135:-1;chr21:20015136-20360113:0;chr21:20360114-20362485:1;chr21:20362486-20733323:0;chr21:20733324-20757352:1;chr21:20757353-20757352:0;chr21:20757353-20761128:1;chr21:20761129-20952099:0;chr21:20952100-21014000:1;chr21:21014001-22468583:0;chr21:22468584-22469083:1;chr21:22469084-22469083:0;chr21:22469084-22502342:1;chr21:22502343-23709351:0;chr21:23709352-23709502:1;chr21:23709503-23710997:0;chr21:23710998-23711526:1;chr21:23711527-24098484:0;chr21:24098485-24098673:1;chr21:24098674-24098673:0;chr21:24098674-24099924:1;chr21:24099925-25212800:0;chr21:25212801-25250237:1;chr21:25250238-26086164:0;chr21:26086165-26087253:1;chr21:26087254-27239900:0;chr21:27239901-27389689:-1;chr21:27389690-27389689:0;chr21:27389690-27390165:1;chr21:27390166-27390165:0;chr21:27390166-27390631:1;chr21:27390632-27390631:0;chr21:27390632-27390693:1;chr21:27390694-27390693:0;chr21:27390694-27519874:-1;chr21:27519875-27519874:0;chr21:27519875-27520083:1;chr21:27520084-27520083:0;chr21:27520084-27613300:-1;chr21:27613301-27613300:0;chr21:27613301-27647654:1;chr21:27647655-27647654:0;chr21:27647655-28018636:-1;chr21:28018637-28018636:0;chr21:28018637-28048546:1;chr21:28048547-28048546:0;chr21:28048547-28068975:-1;chr21:28068976-28100600:0;chr21:28100601-28196166:-1;chr21:28196167-28196166:0;chr21:28196167-28197654:1;chr21:28197655-28197654:0;chr21:28197655-28215211:-1;chr21:28215212-28215362:0;chr21:28215363-28269686:-1;chr21:28269687-28269686:0;chr21:28269687-28269800:1;chr21:28269801-28270600:0;chr21:28270601-28272295:1;chr21:28272296-28272295:0;chr21:28272296-28279800:1;chr21:28279801-28279800:0;chr21:28279801-28453059:-1;chr21:28453060-28453059:0;chr21:28453060-28493255:1;chr21:28493256-28493255:0;chr21:28493256-28562946:-1;chr21:28562947-28672982:0;chr21:28672983-28673379:1;chr21:28673380-29071294:0;chr21:29071295-29124991:1;chr21:29124992-29168262:0;chr21:29168263-29169631:1;chr21:29169632-33749696:0;chr21:33749697-33760820:1;chr21:33760821-34836894:0;chr21:34836895-34847200:1;chr21:34847201-35294725:0;chr21:35294726-35297900:1;chr21:35297901-35303900:0;chr21:35303901-35306052:1;chr21:35306053-36710336:0;chr21:36710337-36732356:1;chr21:36732357-40606037:0;chr21:40606038-40606453:1;chr21:40606454-40606453:0;chr21:40606454-40606700:1;chr21:40606701-40740500:0;chr21:40740501-40750741:1;chr21:40750742-40912519:0;chr21:40912520-40991968:1;chr21:40991969-40991968:0;chr21:40991969-40994770:1;chr21:40994771-43019760:0;chr21:43019761-43054922:1;chr21:43054923-43136200:0;chr21:43136201-43144305:1;chr21:43144306-43928441:0;chr21:43928442-43929366:1;chr21:43929367-43929366:0;chr21:43929367-43929817:1;chr21:43929818-43929817:0;chr21:43929818-43930067:1;chr21:43930068-43930067:0;chr21:43930068-43939218:1;chr21:43939219-43939218:0;chr21:43939219-43940203:1;chr21:43940204-45269600:0;chr21:45269601-45332429:1;chr21:45332430-45332429:0;chr21:45332430-45332976:1;chr21:45332977-45332976:0;chr21:45332977-45333320:1;chr21:45333321-45537792:0;chr21:45537793-45539006:1;chr21:45539007-45539006:0;chr21:45539007-45544694:1;chr21:45544695-46147800:0;chr21:46147801-46193199:1;chr21:46193200-47793777:0;chr21:47793778-47850253:1;chr21:47850254-47859765:0;chr21:47859766-47860000:1;chr21:47860001-48129895:0;chr22:0-19222808:0;chr22:19222809-20304300:-1;chr22:20304301-21797000:0;chr22:21797001-24875900:-1;chr22:24875901-24905006:0;chr22:24905007-51234500:-1;chr22:51234501-51304566:0;chr2:0-243199373:0;chr3:0-126702900:0;chr3:126702901-126757700:-1;chr3:126757701-198022430:0;chr4:0-128100:0;chr4:10035301-10035300:0;chr4:10035301-10077200:1;chr4:1004829-1019006:-1;chr4:10077201-10077200:0;chr4:10077201-10106920:1;chr4:10106921-10106920:0;chr4:10106921-10132000:1;chr4:10132001-10258600:0;chr4:1019007-1019006:0;chr4:1019007-1112519:1;chr4:10258601-10313461:1;chr4:10313462-10313461:0;chr4:10313462-10386136:1;chr4:10386137-10386136:0;chr4:10386137-10568323:1;chr4:10568324-10568323:0;chr4:10568324-10584900:1;chr4:10584901-10584900:0;chr4:10584901-10685300:1;chr4:10685301-10685300:0;chr4:10685301-10802442:1;chr4:10802443-10802442:0;chr4:10802443-10861617:1;chr4:10861618-10918700:0;chr4:10918701-10942110:1;chr4:10942111-10954510:0;chr4:10954511-11034659:1;chr4:11034660-11034659:0;chr4:11034660-11045614:1;chr4:11045615-11045614:0;chr4:11045615-11091600:1;chr4:11091601-11174323:0;chr4:1112520-1127900:0;chr4:11174324-11254800:1;chr4:11254801-11527598:0;chr4:1127901-1150292:1;chr4:1150293-1528662:0;chr4:11527599-11539501:1;chr4:11539502-11539501:0;chr4:11539502-11591400:1;chr4:11591401-11591400:0;chr4:11591401-11637281:1;chr4:11637282-11637281:0;chr4:11637282-11671200:1;chr4:11671201-11671200:0;chr4:11671201-11773861:1;chr4:11773862-11792275:0;chr4:11792276-11860459:1;chr4:11860460-11867169:0;chr4:11867170-11940464:1;chr4:11940465-11982200:0;chr4:11982201-12163625:1;chr4:12163626-12212793:0;chr4:12212794-12229246:1;chr4:12229247-12321013:0;chr4:12321014-12430500:1;chr4:12430501-12430500:0;chr4:12430501-12462119:1;chr4:12462120-12462119:0;chr4:12462120-12482500:1;chr4:12482501-12482500:0;chr4:12482501-12501420:1;chr4:12501421-12501420:0;chr4:12501421-12548600:1;chr4:12548601-12548600:0;chr4:12548601-12556883:1;chr4:12556884-12556883:0;chr4:12556884-12582000:1;chr4:12582001-12582000:0;chr4:12582001-12623023:1;chr4:12623024-12623023:0;chr4:12623024-12646957:1;chr4:12646958-12646957:0;chr4:12646958-12743500:1;chr4:12743501-12743500:0;chr4:12743501-12776688:1;chr4:12776689-12776688:0;chr4:12776689-12820166:1;chr4:128101-168961:1;chr4:12820167-12820166:0;chr4:12820167-12842800:1;chr4:12842801-12842900:0;chr4:12842901-12844401:1;chr4:12844402-12844401:0;chr4:12844402-12905200:1;chr4:12905201-12911000:0;chr4:12911001-12955200:1;chr4:12955201-12955200:0;chr4:12955201-13027525:1;chr4:13027526-13027525:0;chr4:13027526-13066700:1;chr4:13066701-13066700:0;chr4:13066701-13073219:1;chr4:13073220-13073219:0;chr4:13073220-13084815:1;chr4:13084816-13112575:0;chr4:13112576-13113854:1;chr4:13113855-13618700:0;chr4:13618701-13642506:1;chr4:13642507-13642506:0;chr4:13642507-13652300:1;chr4:13652301-13652300:0;chr4:13652301-13669637:1;chr4:13669638-13669637:0;chr4:13669638-13792800:1;chr4:13792801-13809600:0;chr4:13809601-13827400:1;chr4:13827401-13827400:0;chr4:13827401-13847799:1;chr4:13847800-13847799:0;chr4:13847800-13877200:1;chr4:13877201-13877200:0;chr4:13877201-13902877:1;chr4:13902878-13902877:0;chr4:13902878-13934600:1;chr4:13934601-13934600:0;chr4:13934601-13986648:1;chr4:13986649-13986648:0;chr4:13986649-13999101:1;chr4:13999102-14113800:0;chr4:14113801-14141800:1;chr4:14141801-14141800:0;chr4:14141801-14159123:1;chr4:14159124-14159123:0;chr4:14159124-14185320:1;chr4:14185321-14185320:0;chr4:14185321-14187044:1;chr4:14187045-14220307:0;chr4:14220308-14300643:1;chr4:14300644-14300643:0;chr4:14300644-14441746:1;chr4:14441747-14441746:0;chr4:14441747-14485000:1;chr4:14485001-14489000:0;chr4:14489001-14510580:1;chr4:14510581-14510580:0;chr4:14510581-14598348:1;chr4:14598349-14608901:0;chr4:14608902-14620400:1;chr4:14620401-14781533:0;chr4:14781534-14840491:1;chr4:14840492-14840491:0;chr4:14840492-14841200:1;chr4:14841201-14842600:0;chr4:14842601-15003400:1;chr4:15003401-15003400:0;chr4:15003401-15087100:1;chr4:15087101-15087200:0;chr4:15087201-15211600:1;chr4:15211601-15211600:0;chr4:15211601-15236000:1;chr4:15236001-15236000:0;chr4:15236001-15272400:1;chr4:15272401-15272400:0;chr4:15272401-15321200:1;chr4:1528663-1693335:1;chr4:15321201-15329030:0;chr4:15329031-15329939:1;chr4:15329940-15329939:0;chr4:15329940-15375288:1;chr4:15375289-15375288:0;chr4:15375289-15388094:1;chr4:15388095-15411375:0;chr4:15411376-15442500:1;chr4:15442501-15442500:0;chr4:15442501-15551700:1;chr4:15551701-15551700:0;chr4:15551701-15560810:1;chr4:15560811-15560810:0;chr4:15560811-15571908:1;chr4:15571909-15571908:0;chr4:15571909-15579000:1;chr4:15579001-15579000:0;chr4:15579001-15598000:1;chr4:15598001-15598000:0;chr4:15598001-15622529:1;chr4:15622530-15622529:0;chr4:15622530-15644962:1;chr4:15644963-15644962:0;chr4:15644963-15790991:1;chr4:15790992-15790991:0;chr4:15790992-15852500:1;chr4:15852501-15852500:0;chr4:15852501-15864000:1;chr4:15864001-15864000:0;chr4:15864001-15890673:1;chr4:15890674-15890673:0;chr4:15890674-16214801:1;chr4:16214802-16214801:0;chr4:16214802-16223986:1;chr4:16223987-16223986:0;chr4:16223987-16244562:1;chr4:16244563-16244562:0;chr4:16244563-16268000:1;chr4:16268001-16268000:0;chr4:16268001-16309930:1;chr4:16309931-16309930:0;chr4:16309931-16404000:1;chr4:16404001-16408700:0;chr4:16408701-16452591:1;chr4:16452592-16489355:0;chr4:16489356-16489683:1;chr4:16489684-16489683:0;chr4:16489684-16522142:1;chr4:16522143-16611215:0;chr4:16611216-16656636:1;chr4:16656637-16656636:0;chr4:16656637-16725800:1;chr4:16725801-16725800:0;chr4:16725801-16961272:1;chr4:168962-215151:0;chr4:1693336-1693335:0;chr4:1693336-1713500:1;chr4:16961273-16988353:0;chr4:16988354-17029000:1;chr4:17029001-17029000:0;chr4:17029001-17132300:1;chr4:17132301-17132400:0;chr4:17132401-17157900:1;chr4:1713501-1713500:0;chr4:1713501-1736258:1;chr4:17157901-17157900:0;chr4:17157901-17158437:1;chr4:17158438-17158437:0;chr4:17158438-17187500:1;chr4:17187501-17187500:0;chr4:17187501-17386515:1;chr4:173433501-190987600:1;chr4:1736259-2082280:0;chr4:17386516-17386515:0;chr4:17386516-17390792:1;chr4:17390793-17521625:0;chr4:17521626-17608300:1;chr4:17608301-17769400:0;chr4:17769401-17816979:1;chr4:17816980-17830300:0;chr4:17830301-17847900:1;chr4:17847901-17863900:0;chr4:17863901-18064539:1;chr4:18064540-18103600:0;chr4:18103601-18163600:1;chr4:18163601-18163600:0;chr4:18163601-18239800:1;chr4:18239801-18616000:0;chr4:18616001-18785772:1;chr4:18785773-23472272:0;chr4:190987601-191154276:0;chr4:2082281-2248800:1;chr4:215152-248200:1;chr4:2248801-2248800:0;chr4:2248801-2471700:1;chr4:23472273-23472830:1;chr4:23472831-25678800:0;chr4:2471701-2471700:0;chr4:2471701-2609210:1;chr4:248201-248200:0;chr4:248201-332766:1;chr4:25678801-25811400:1;chr4:25811401-31784026:0;chr4:2609211-2609210:0;chr4:2609211-2661207:1;chr4:2661208-2661207:0;chr4:2661208-2761817:1;chr4:2761818-2761817:0;chr4:2761818-2862400:1;chr4:2862401-2862400:0;chr4:2862401-3014600:1;chr4:3014601-3051500:0;chr4:3051501-3081100:1;chr4:3081101-3081100:0;chr4:3081101-3185733:1;chr4:31784027-40407000:1;chr4:3185734-3185733:0;chr4:3185734-3185979:1;chr4:3185980-3185979:0;chr4:3185980-3198611:1;chr4:3198612-3198611:0;chr4:3198612-3306753:1;chr4:3306754-3388539:0;chr4:332767-332766:0;chr4:332767-519422:1;chr4:3388540-3451700:1;chr4:3451701-3451700:0;chr4:3451701-3502251:1;chr4:3502252-3565100:0;chr4:3565101-4175221:1;chr4:40407001-87711443:0;chr4:4175222-4175221:0;chr4:4175222-4263200:1;chr4:4263201-4285300:0;chr4:4285301-4326262:1;chr4:4326263-4341461:0;chr4:4341462-4357600:1;chr4:4357601-4357600:0;chr4:4357601-4385167:1;chr4:4385168-4432269:0;chr4:4432270-4432433:1;chr4:4432434-4432433:0;chr4:4432434-4432524:1;chr4:4432525-4447027:0;chr4:4447028-4626897:1;chr4:4626898-4690494:0;chr4:4690495-4728000:1;chr4:4728001-4768300:0;chr4:4768301-4795563:1;chr4:4795564-4823322:0;chr4:4823323-4842400:1;chr4:4842401-4897100:0;chr4:4897101-4940438:1;chr4:4940439-4969857:0;chr4:4969858-4970085:1;chr4:4970086-4970085:0;chr4:4970086-5020900:1;chr4:5020901-5030985:0;chr4:5030986-5065571:1;chr4:5065572-5065571:0;chr4:5065572-5082059:1;chr4:5082060-5082059:0;chr4:5082060-5094300:1;chr4:5094301-5094300:0;chr4:5094301-5255355:1;chr4:519423-1004828:0;chr4:5255356-5255355:0;chr4:5255356-5269683:1;chr4:5269684-5269683:0;chr4:5269684-5270014:1;chr4:5270015-5270014:0;chr4:5270015-5468800:1;chr4:5468801-5468800:0;chr4:5468801-5592907:1;chr4:5592908-5592907:0;chr4:5592908-5594590:1;chr4:5594591-5594590:0;chr4:5594591-5722644:1;chr4:5722645-5722644:0;chr4:5722645-5839322:1;chr4:5839323-5839322:0;chr4:5839323-5887539:1;chr4:5887540-5887539:0;chr4:5887540-6031900:1;chr4:6031901-6303153:0;chr4:6303154-6355400:1;chr4:6355401-6355400:0;chr4:6355401-6572289:1;chr4:6572290-6572289:0;chr4:6572290-6586600:1;chr4:6586601-6626400:0;chr4:6626401-6643848:1;chr4:6643849-6705694:0;chr4:6705695-6759828:1;chr4:6759829-6759828:0;chr4:6759829-6843868:1;chr4:6843869-6843868:0;chr4:6843869-6872325:1;chr4:6872326-6872325:0;chr4:6872326-6872676:1;chr4:6872677-6872676:0;chr4:6872677-6889518:1;chr4:6889519-6889518:0;chr4:6889519-6911100:1;chr4:6911101-6911100:0;chr4:6911101-7076670:1;chr4:7076671-7076670:0;chr4:7076671-7119900:1;chr4:7119901-7119900:0;chr4:7119901-7132600:1;chr4:7132601-7132600:0;chr4:7132601-7151600:1;chr4:7151601-7151600:0;chr4:7151601-7174876:1;chr4:7174877-7174876:0;chr4:7174877-7177000:1;chr4:7177001-7177000:0;chr4:7177001-7222100:1;chr4:7222101-7222100:0;chr4:7222101-7236609:1;chr4:7236610-7236609:0;chr4:7236610-7262118:1;chr4:7262119-7262118:0;chr4:7262119-7273557:1;chr4:7273558-7273557:0;chr4:7273558-7275881:1;chr4:7275882-7275881:0;chr4:7275882-7353305:1;chr4:7353306-7353305:0;chr4:7353306-7353409:1;chr4:7353410-7353409:0;chr4:7353410-7360125:1;chr4:7360126-7479723:0;chr4:7479724-7525389:1;chr4:7525390-7525389:0;chr4:7525390-7537448:1;chr4:7537449-7537448:0;chr4:7537449-7538280:1;chr4:7538281-7538280:0;chr4:7538281-7545699:1;chr4:7545700-7545699:0;chr4:7545700-7573363:1;chr4:7573364-7573363:0;chr4:7573364-7593000:1;chr4:7593001-7593000:0;chr4:7593001-7609500:1;chr4:7609501-7609500:0;chr4:7609501-7618569:1;chr4:7618570-7618569:0;chr4:7618570-7679866:1;chr4:7679867-7679866:0;chr4:7679867-7706140:1;chr4:7706141-7730441:0;chr4:7730442-7835200:1;chr4:7835201-7870054:0;chr4:7870055-7888600:1;chr4:7888601-7916000:0;chr4:7916001-7972000:1;chr4:7972001-8009900:0;chr4:8009901-8036960:1;chr4:8036961-8050447:0;chr4:8050448-8071870:1;chr4:8071871-8088000:0;chr4:8088001-8153477:1;chr4:8153478-8153847:0;chr4:8153848-8231600:1;chr4:8231601-8231652:0;chr4:8231653-8292267:1;chr4:8292268-8300629:0;chr4:8300630-8416530:1;chr4:8416531-8416530:0;chr4:8416531-8468000:1;chr4:8468001-8468000:0;chr4:8468001-9040400:1;chr4:87711444-89268900:1;chr4:89268901-89268900:0;chr4:89268901-90151000:1;chr4:90151001-90151000:0;chr4:90151001-90406667:1;chr4:9040401-9370700:0;chr4:90406668-90446978:0;chr4:90446979-90453692:1;chr4:90453693-90453692:0;chr4:90453693-90648646:1;chr4:90648647-91457402:0;chr4:91457403-91931000:1;chr4:91931001-91938400:0;chr4:91938401-92377715:1;chr4:92377716-173433500:0;chr4:9370701-9570400:1;chr4:9570401-9608500:0;chr4:9608501-9630700:1;chr4:9630701-9778638:0;chr4:9778639-9837603:1;chr4:9837604-9856776:0;chr4:9856777-9971993:1;chr4:9971994-10035300:1;chr4:9971994-9971993:0;chr5:0-11700:0;chr5:11701-1667900:-1;chr5:13827758-49441600:0;chr5:1667901-1715900:0;chr5:1715901-13827757:-1;chr5:180736101-180915260:0;chr5:49441601-180736100:-1;chr6:0-14990246:0;chr6:102683927-113517100:1;chr6:113517101-113517100:0;chr6:113517101-114052400:1;chr6:114052401-124696495:0;chr6:124696496-124697192:-1;chr6:124697193-150282316:0;chr6:14990247-14993614:1;chr6:14993615-70911318:0;chr6:150282317-163675000:1;chr6:163675001-163675000:0;chr6:163675001-167938348:1;chr6:167938349-171115067:0;chr6:70911319-73310609:1;chr6:73310610-73310609:0;chr6:73310610-90641880:1;chr6:90641881-90642088:0;chr6:90642089-92815599:1;chr6:92815600-92815599:0;chr6:92815600-92816439:1;chr6:92816440-92816439:0;chr6:92816440-92816535:1;chr6:92816536-102683926:0;chr7:0-2671300:0;chr7:113714901-113732100:0;chr7:113732101-159128500:1;chr7:159128501-159138663:0;chr7:2671301-4758700:1;chr7:45110801-45129300:0;chr7:45129301-113714900:1;chr7:4758701-4878000:0;chr7:4878001-45110800:1;chr8:0-100700:0;chr8:100701-11404300:1;chr8:11404301-11430500:0;chr8:11430501-85623200:1;chr8:142366901-142366900:0;chr8:142366901-143524000:1;chr8:143524001-143626600:0;chr8:143626601-144524900:1;chr8:144524901-144524900:0;chr8:144524901-144544300:1;chr8:144544301-144855400:0;chr8:144855401-144869500:1;chr8:144869501-146364022:0;chr8:85623201-85643300:0;chr8:85643301-142366900:1;chr9:0-10000:0;chr9:10001-96051100:1;chr9:137215601-137331600:0;chr9:137331601-138570100:1;chr9:138570101-138684500:0;chr9:138684501-138812900:1;chr9:138812901-139591400:0;chr9:139591401-139606200:1;chr9:139606201-139754300:0;chr9:139754301-139834200:1;chr9:139834201-140176400:0;chr9:140176401-140189200:1;chr9:140189201-141213431:0;chr9:96051101-96071100:0;chr9:96071101-137215600:1;chrX:0-155270560:0;chrY:0-59373566:0 hs1:27330887-27330887,hs4:7353306-7353306;hs1:3350094-3350094,hs4:1149965-1149965;hs1:46625708-46625708,hs4:16656637-16656637;hs1:25563490-25563490,hs1:22993321-22993321;hs1:67223853-67223853,hs17:45190533-45190533;hs1:114007460-114007460,hs1:114004509-114004509;hs4:90091273-90091273,hs4:92130987-92130987;hs4:4175222-4175222,hs4:1693336-1693336;hs4:3185734-3185734,hs4:4969858-4969858;hs4:7573364-7573364,hs4:6705695-6705695;hs4:15644963-15644963,hs4:9377740-9377740;hs4:7481271-7481271,hs4:3185980-3185980;hs4:16611216-16611216,hs1:35921415-35921415;hs4:11867170-11867170,hs4:8153848-8153848;hs4:3388540-3388540,hs4:1218818-1218818;hs4:5594591-5594591,hs4:7353410-7353410;hs4:14220308-14220308,hs4:10568324-10568324;hs4:5594591-5594591,hs4:7353410-7353410;hs4:90648647-90648647,hs4:89689608-89689608;hs4:91175983-91175983,hs4:89598157-89598157;hs4:185400548-185400548,hs1:2996921-2996921;hs4:7198795-7198795,hs4:3502252-3502252;hs4:5594591-5594591,hs4:7353410-7353410;hs4:12842803-12842803,hs4:7076671-7076671;hs4:7481271-7481271,hs4:3185980-3185980;hs4:5887540-5887540,hs4:13847800-13847800;hs4:14159124-14159124,hs4:8584400-8584400;hs4:3854776-3854776,hs4:16399167-16399167;hs4:10482690-10482690,hs4:12655960-12655960;hs4:7481271-7481271,hs4:3185980-3185980;hs4:15061437-15061437,hs4:519423-519423;hs4:10954511-10954511,hs4:4823323-4823323;hs4:14936928-14936928,hs4:16223987-16223987;hs4:7481271-7481271,hs4:3185980-3185980;hs4:3388540-3388540,hs4:1218818-1218818;hs4:5594591-5594591,hs4:7353410-7353410;hs4:3388540-3388540,hs4:1218818-1218818;hs4:14936928-14936928,hs4:16223987-16223987;hs4:90648647-90648647,hs4:89689608-89689608;hs4:3388540-3388540,hs4:1218818-1218818;hs4:7481271-7481271,hs4:3185980-3185980;hs4:5594591-5594591,hs4:7353410-7353410;hs4:13113855-13113855,hs1:39393589-39393589;hs4:15061437-15061437,hs4:519423-519423;hs4:12163626-12163626,hs1:19816708-19816708;hs4:3818960-3818960,hs1:842580-842580;hs4:91175983-91175983,hs4:89598157-89598157;hs4:92145791-92145791,hs4:91671399-91671399;hs4:9127345-9127345,hs4:13748063-13748063;hs4:4795564-4795564,hs4:14187045-14187045;hs4:13753358-13753358,hs4:9608291-9608291;hs4:15571909-15571909,hs4:9837604-9837604;hs4:23472273-23472273,hs4:1528663-1528663;hs4:1004829-1004829,hs6:157352866-157352866;hs4:92145791-92145791,hs4:91671399-91671399;hs4:92145791-92145791,hs4:91671399-91671399;hs4:18491081-18491081,hs4:17158080-17158080;hs4:5594591-5594591,hs4:7353410-7353410;hs4:16489684-16489684,hs6:124696496-124696496;hs4:13767424-13767424,hs4:13986649-13986649;hs4:14738549-14738549,hs4:8416531-8416531;hs4:1545099-1545099,hs4:17386516-17386516;hs4:91175983-91175983,hs4:89598157-89598157;hs4:3388540-3388540,hs4:1218818-1218818;hs4:5594591-5594591,hs4:7353410-7353410;hs4:9040726-9040726,hs4:12862793-12862793;hs4:3388540-3388540,hs4:1218818-1218818;hs4:5594591-5594591,hs4:7353410-7353410;hs4:14936928-14936928,hs4:16223987-16223987;hs4:7273558-7273558,hs17:56033154-56033154;hs4:4326263-4326263,hs1:35581090-35581090;hs4:16611216-16611216,hs1:35921415-35921415;hs4:10106921-10106921,hs4:9856777-9856777;hs4:3239227-3239227,hs4:215152-215152;hs4:3388540-3388540,hs4:1218818-1218818;hs4:6899689-6899689,hs4:8231653-8231653;hs4:3388540-3388540,hs4:1218818-1218818;hs4:149030463-149030463,hs17:61957735-61957735;hs4:5594591-5594591,hs4:7353410-7353410;hs4:5594591-5594591,hs4:7353410-7353410;hs4:5594591-5594591,hs4:7353410-7353410;hs4:7481271-7481271,hs4:3185980-3185980;hs4:3388540-3388540,hs4:1218818-1218818;hs4:3388540-3388540,hs4:1218818-1218818;hs4:5594591-5594591,hs4:7353410-7353410;hs4:3239227-3239227,hs4:215152-215152;hs4:5594591-5594591,hs4:7353410-7353410;hs4:12548601-12548601,hs1:3349156-3349156;hs4:11940465-11940465,hs4:16916840-16916840;hs4:13913046-13913046,hs4:9143987-9143987;hs4:3388540-3388540,hs4:1218818-1218818;hs4:16452592-16452592,hs5:45917687-45917687;hs4:7481271-7481271,hs4:3185980-3185980;hs4:6643849-6643849,hs4:6643971-6643971;hs4:6759829-6759829,hs4:3776986-3776986;hs4:1571668-1571668,hs4:7706141-7706141;hs4:10106921-10106921,hs4:9856777-9856777;hs4:12501421-12501421,hs4:11539502-11539502;hs4:7481271-7481271,hs4:3185980-3185980;hs4:5594591-5594591,hs4:7353410-7353410;hs4:3306754-3306754,hs4:12646958-12646958;hs4:2018795-2018795,hs4:4626898-4626898;hs4:10342624-10342624,hs4:5065572-5065572;hs4:31784027-31784027,hs17:43239301-43239301;hs4:1814510-1814510,hs17:48026211-48026211;hs4:7481271-7481271,hs4:3185980-3185980;hs4:5594591-5594591,hs4:7353410-7353410;hs5:923093-923093,hs6:36975893-36975893;hs5:22445957-22445957,hs4:8712217-8712217;hs6:124697193-124697193,hs5:13827758-13827758;hs6:35961976-35961976,hs5:1314500-1314500;hs6:14254308-14254308,hs17:38316714-38316714;hs6:40430716-40430716,hs22:22328769-22328769;hs6:44071617-44071617,hs6:25378133-25378133;hs6:97317076-97317076,hs6:97317574-97317574;hs6:50143061-50143061,hs22:18396097-18396097;hs6:17672213-17672213,hs6:35583238-35583238;hs6:50142804-50142804,hs22:23180981-23180981;hs6:49653421-49653421,hs6:855705-855705;hs6:40430716-40430716,hs22:22328769-22328769;hs6:43373785-43373785,hs6:24689527-24689527;hs6:29964841-29964841,hs6:18370918-18370918;hs6:142548996-142548996,hs4:1019007-1019007;hs6:17672213-17672213,hs6:35583238-35583238;hs6:46659043-46659043,hs17:41621473-41621473;hs6:18051013-18051013,hs21:38710526-38710526;hs6:72748861-72748861,hs6:853354-853354;hs6:67327482-67327482,hs17:38329391-38329391;hs6:3448228-3448228,hs6:37697949-37697949;hs6:44277371-44277371,hs6:41375450-41375450;hs13:35683108-35683108,hs15:35887172-35887172;hs13:35683108-35683108,hs15:35887172-35887172;hs17:63339931-63339931,hs6:102683927-102683927;hs17:39459217-39459217,hs6:15374541-15374541;hs17:41020099-41020099,hs6:38630568-38630568;hs17:56182969-56182969,hs17:53820187-53820187;hs17:38898721-38898721,hs6:12544051-12544051;hs17:57456215-57456215,hs4:11174324-11174324;hs18:48955512-48955512,hs18:49331768-49331768;hs19:38964670-38964670,hs19:31808786-31808786;hs19:37857292-37857292,hs19:36921609-36921609;hs19:37162851-37162851,hs19:28958146-28958146;hs21:35818784-35818784,hs21:38711218-38711218;hs21:38414998-38414998,hs21:22468584-22468584;hs21:27389777-27389777,hs21:15821088-15821088;hs21:47793778-47793778,hs21:45332430-45332430;hs21:27520084-27520084,hs21:28215363-28215363;hs21:17397166-17397166,hs21:18814923-18814923;hs21:17830370-17830370,hs21:22502343-22502343;hs21:14423021-14423021,hs21:45539007-45539007;hs21:40606038-40606038,hs21:17613945-17613945;hs21:40606038-40606038,hs21:17613945-17613945;hs21:26213989-26213989,hs21:34220201-34220201;hs21:17830370-17830370,hs21:22502343-22502343;hs21:43361267-43361267,hs21:11180023-11180023;hs21:14423021-14423021,hs21:45539007-45539007;hs21:40606038-40606038,hs21:17613945-17613945;hs21:15823979-15823979,hs21:47814047-47814047;hs21:40606038-40606038,hs21:17613945-17613945;hs21:43930068-43930068,hs21:43054898-43054898;hs21:16617754-16617754,hs4:56497-56497;hs21:17830370-17830370,hs21:22502343-22502343;hs21:24605728-24605728,hs21:35743245-35743245;hs21:47792823-47792823,hs21:34216923-34216923;hs21:27520084-27520084,hs21:28215363-28215363;hs21:17830370-17830370,hs21:22502343-22502343;hs21:28562947-28562947,hs21:16399608-16399608;hs21:15702728-15702728,hs21:45544695-45544695;hs21:27520084-27520084,hs21:28215363-28215363;hs21:29124992-29124992,hs21:47850254-47850254;hs21:17830370-17830370,hs21:22502343-22502343;hs21:40606038-40606038,hs21:17613945-17613945;hs21:20011004-20011004,hs6:14450221-14450221;hs21:47793972-47793972,hs21:16686725-16686725;hs21:41813968-41813968,hs6:30036042-30036042;hs21:47793778-47793778,hs21:45332430-45332430;hs21:27390694-27390694,hs21:22469084-22469084;hs21:27520084-27520084,hs21:28215363-28215363;hs21:40606038-40606038,hs21:17613945-17613945;hs21:27520084-27520084,hs21:28215363-28215363;hs21:17830370-17830370,hs21:22502343-22502343;hs21:15686717-15686717,hs19:32246452-32246452;hs21:17830370-17830370,hs21:22502343-22502343;hs21:17830370-17830370,hs21:22502343-22502343;hs21:17830370-17830370,hs21:22502343-22502343;hs21:36710337-36710337,hs21:28068976-28068976;hs21:27520084-27520084,hs21:28215363-28215363;hs21:40606038-40606038,hs21:17613945-17613945;hs21:41813968-41813968,hs6:30036042-30036042;hs21:27520084-27520084,hs21:28215363-28215363;hs21:17830370-17830370,hs21:22502343-22502343;hs21:20761129-20761129,hs21:29574135-29574135;hs21:43054923-43054923,hs21:43930068-43930068;hs21:16617754-16617754,hs4:56497-56497;hs21:17830370-17830370,hs21:22502343-22502343;hs21:28196167-28196167,hs21:14381405-14381405;hs21:41812829-41812829,hs21:20015136-20015136;hs21:40250537-40250537,hs21:10702705-10702705;hs21:40606038-40606038,hs21:17613945-17613945;hs21:17830370-17830370,hs21:22502343-22502343;hs21:26087254-26087254,hs21:29760660-29760660;hs21:40606038-40606038,hs21:17613945-17613945 ABCG2;ABLIM2;ACOX3;ADD1;ADRA2C;AFAP1;AFF1;ARAP2;BOD1L;C15orf41;C17orf99;C18orf54;C19orf12;C1orf123;C1orf127;C1orf216;C1orf64;C1orf87;C1QTNF7;C22orf39;C4orf19;C4orf36;C4orf44;C4orf6;C5orf38;C6orf118;C7orf60;C9orf129;C9orf66;C9orf89;CC2D2A;CCDC96;CD38;CHRNA9;CLNK;CLRN2;CNO;CPEB2;CPZ;CRMP1;CTBP1;CYTL1;DCAF16;DEFB131;DOK7;DRD5;DTHD1;EVC;EVC2;FAM13A;FAM184B;FAM190A;FAM193A;FAM200B;FAM53A;FBXL5;FGFBP1;FGFBP2;FGFRL1;GAK;GALNT7;GALNTL6;GPCRLTM7;GPR78;GPRIN3;GRK4;GRPEL1;HAUS3;HERC3;HERC5;HERC6;HGFAC;HMGB2;HMX1;HTRA3;HTT;JAKMIP1;KIAA0232;KIAA1239;KLHL8;LAP3;LCORL;LDB2;LOC100128071;LOC100288255;LOC100507266;LOC100507466;LOC388588;LOC388630;LOC402160;LOC441009;LOC646627;LOC653486;LOC729059;LYAR;MAN2B2;MEPE;METTL19;MFSD10;MRFAP1;MRFAP1L1;MXD4;N4BP2;NAP1L5;NCAPG;NOP14;NR3C2;OTOP1;PDS5A;PIGG;PIGY;PKD2;POLN;PPM1K;PPP2R2C;PROM1;PTPN13;RELL1;RGS12;RHOH;RNF212;RNF4;SAP30;SCRG1;SEL1L3;SH3BP2;SH3TC1;SLBP;SLC10A6;SLC2A9;SLC34A2;SNCA;SORCS2;SPP1;STK32B;STX18;TACC3;TADA2B;TAPT1;TBC1D14;TIGD2;TMEM128;TMEM129;TNIP2;TRIML1;TRIML2;UBE2K;UGT2A3;UGT2B10;UGT2B15;UGT2B17;WDR1;WFS1;ZBTB49;ZFYVE28;ZNF141;ZNF518B;ZNF595;ZNF718;ZNF721;ZNF732;ZNF876P; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes ABLIM2,CRMP1;AFAP1,CTBP1;AFAP1,GAK;C1QTNF7,SORCS2;CC2D2A,SLC2A9;CTBP1,RGS12;EVC2,CTBP1;EVC2,GAK;FAM190A,PTPN13;GAK,CTBP1;GAK,GAK;HTT,HTT;HTT,STK32B;METTL19,EVC;MMRN1,FAM190A;SORCS2,CTBP1;SORCS2,EVC2;SORCS2,GAK;STK32B,HTT;TAPT1,LDB2 CTDB0399 Research 24705251 Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, Baker SJ The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma Nature Genetics 2014 May 8 Glioma Next Generation Sequencing Homo sapiens SJHGG102_D Illumina Genome Analyzer IIx or HiSeq chr10:0-135534747:0;chr11:0-168400:0;chr11:168401-494000:-1;chr11:20127589-50038678:-1;chr11:494001-20127588:0;chr11:50038679-135006516:0;chr12:0-60700:0;chr12:26585601-26598431:0;chr12:26598432-26707500:-1;chr12:26707501-45876957:0;chr12:45876958-45877154:-1;chr12:45877155-133851895:0;chr12:60701-26585600:-1;chr13:0-19258900:0;chr13:19258901-63669725:-1;chr13:63669726-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-60000:0;chr16:53839945-53839944:0;chr16:53839945-54055500:-1;chr16:54055501-54055500:0;chr16:54055501-70885700:-1;chr16:60001-53839944:-1;chr16:70885701-70885700:0;chr16:70885701-71203200:-1;chr16:71203201-71203200:0;chr16:71203201-90292700:-1;chr16:90292701-90354753:0;chr17:0-81195210:0;chr18:0-46100:0;chr18:15401401-78077248:0;chr18:46101-15401400:-1;chr19:0-158500:0;chr19:158501-18524013:1;chr19:18524014-40580700:0;chr19:40580701-59118800:-1;chr19:59118801-59128983:0;chr1:0-72071933:0;chr1:144858001-233905930:1;chr1:233905931-233906010:0;chr1:233906011-249240500:1;chr1:249240501-249250621:0;chr1:72071934-72086469:-1;chr1:72086470-144858000:0;chr20:0-62402290:0;chr20:62402291-62402433:1;chr20:62402434-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-141631967:0;chr2:141631968-141636539:-1;chr2:141636540-243199373:0;chr3:0-181449282:0;chr3:181449283-181451362:-1;chr3:181451363-198022430:0;chr4:0-20698782:0;chr4:20698783-21280082:-1;chr4:21280083-191154276:0;chr5:0-23162974:0;chr5:23162975-23171910:-1;chr5:23171911-180915260:0;chr6:0-1416736:0;chr6:101075198-101368872:-1;chr6:101368873-171115067:0;chr6:1416737-1416804:1;chr6:1416805-101075197:0;chr7:0-159138663:0;chr8:0-33500:0;chr8:101839998-101839997:0;chr8:101839998-101943345:1;chr8:101943346-101943345:0;chr8:101943346-103133592:-1;chr8:103133593-103133592:0;chr8:103133593-106817517:1;chr8:106817518-106817517:0;chr8:106817518-107163457:-1;chr8:107163458-107163457:0;chr8:107163458-108656775:1;chr8:108656776-108656775:0;chr8:108656776-108659146:1;chr8:108659147-108659146:0;chr8:108659147-108659161:1;chr8:108659162-108659161:0;chr8:108659162-112017267:1;chr8:112017268-117328528:0;chr8:117328529-120150971:1;chr8:120150972-120150971:0;chr8:120150972-120152079:1;chr8:120152080-120152079:0;chr8:120152080-122407264:1;chr8:122407265-122407264:0;chr8:122407265-125730559:1;chr8:125730560-125730559:0;chr8:125730560-126291344:1;chr8:126291345-126291344:0;chr8:126291345-129575905:1;chr8:129575906-129575905:0;chr8:129575906-129873396:1;chr8:129873397-129873396:0;chr8:129873397-136422622:1;chr8:136422623-136422622:0;chr8:136422623-146303800:1;chr8:146303801-146364022:0;chr8:33501-39505783:-1;chr8:39505784-39505783:0;chr8:39505784-39506268:1;chr8:39506269-39506268:0;chr8:39506269-43820800:-1;chr8:43820801-46856500:0;chr8:46856501-51010673:1;chr8:51010674-51010673:0;chr8:51010674-52811277:1;chr8:52811278-52811277:0;chr8:52811278-57828923:1;chr8:57828924-57828923:0;chr8:57828924-57829510:-1;chr8:57829511-57829510:0;chr8:57829511-59576285:1;chr8:59576286-101839997:-1;chr8:59576286-59576285:0;chr9:0-141213431:0;chrX:0-29360200:0;chrX:124406301-124414800:-1;chrX:124414801-155270560:0;chrX:29360201-29453392:-1;chrX:29453393-124406300:0;chrY:0-2649500:0;chrY:2649501-59033300:-1;chrY:59033301-59373566:0 hs1:35091533-35091533,hs1:35090329-35090329;hs1:72071934-72071934,hs14:90264461-90264461;hs1:72071934-72071934,hs14:90264461-90264461;hs2:195687849-195687849,hs2:148240980-148240980;hs3:67944284-67944284,hs6:46985711-46985711;hs8:103133593-103133593,hs8:101839998-101839998;hs8:129873397-129873397,hs8:108656776-108656776;hs8:39506269-39506269,hs8:106817518-106817518;hs8:108659162-108659162,hs8:129575906-129575906;hs10:3914053-3914053,hs1:233763481-233763481;hs10:3914020-3914020,hs1:233763490-233763490;hs15:69804520-69804520,hs17:78660946-78660946;hs19:18524014-18524014,hs19:40580585-40580585 ABRA;ADCY8;ANGPT1;ANKRD46;ASAP1;C8orf22;C8orf33;C8orf4;C8orf42;C8orf85;CA8;CEBPD;CHCHD7;CHD7;CLVS1;COL14A1;COL22A1;COLEC10;COMMD5;CYP7A1;DEPTOR;DERL1;DPYS;DSCC1;EBAG9;EFCAB1;EFR3A;EIF3E;EIF3H;ENPP2;ENY2;EXT1;FAM110B;FAM135B;FAM150A;FAM49B;FAM83A;FAM84B;FBXO25;FNTA;GRHL2;GSDMC;HAS2;HGSNAT;HOOK3;HTRA4;IDO1;IDO2;IMPAD1;KCNK9;KCNV1;KHDRBS3;KIAA0146;KIAA0196;KLF10;LOC283116;LOC646627;LOC653486;LRP12;MAL2;MCM4;MED30;MOS;MRPL13;MTBP;MTSS1;MYC;NCALD;NDRG1;NDUFB9;NOV;NPBWR1;NSMAF;NSMCE2;ODF1;OR4F21;OXR1;PABPC1;PCMTD1;PENK;PKHD1L1;PLAG1;POTEA;POU5F1B;PRKDC;PXDNL;RAB2A;RAD21;RB1CC1;RIMS2;RNF139;RNF19A;RRM2B;RSPO2;SAMD12;SDCBP;SDR16C5;SGK196;SLA;SLC30A8;SNAI2;SNTB1;SNTG1;SNX31;SPAG1;SQLE;ST18;ST3GAL1;SYBU;TAF2;TATDN1;TM2D2;TM7SF4;TMEM74;TNFRSF11B;TOX;TRAPPC9;TRHR;TRIB1;TRMT12;TTC35;UBE2V2;UBR5;UBXN2B;UTP23;WDR67;WISP1;YWHAZ;ZFAT;ZFPM2;ZHX2;ZNF16;ZNF250;ZNF572;ZNF596;ZNF7;ZNF706; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem. GRCh37/hg19 Yes NA CTDB0413 Research 25719666 Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grutzmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA; Australian Pancreatic Cancer Genome Initiative, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, Grimmond SM Whole genomes redefine the mutational landscape of pancreatic cancer Nature 2015 Feb 8 Pancreatic cancer Next Generation Sequencing Homo sapiens ICGC_0004 Illumina HiSeq 2000 chr10:0-69623992:0;chr10:69623993-90200293:-1;chr10:90200294-135534747:0;chr11:0-135006516:0;chr12:0-38096966:0;chr12:38096967-38924661:-1;chr12:38924662-52370131:0;chr12:52370132-52370409:-1;chr12:52370410-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-10849116:0;chr21:10849117-10944185:-1;chr21:10944186-48129895:0;chr22:0-51304566:0;chr2:0-112307636:0;chr2:112307637-112647111:-1;chr2:112647112-243199373:0;chr3:0-198022430:0;chr4:0-160974802:0;chr4:160974803-161098962:-1;chr4:161098963-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-5499065:0;chr8:122709151-129674654:0;chr8:129674655-130526331:-1;chr8:130526332-136409771:0;chr8:136409772-137426384:-1;chr8:137426385-146364022:0;chr8:53079435-108692391:-1;chr8:5499066-5628772:-1;chr8:5628773-53079434:0;chr8:87581785-122709150:-1;chr9:0-9170699:0;chr9:9170700-9523598:-1;chr9:9523599-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs1:33183391-33183391,hs1:33260864-33260864;hs1:38432796-38432796,hs6:28863604-28863604;hs1:49491351-49491351,hs1:49494430-49494430;hs1:174962536-174962536,hs1:174928636-174928636;hs2:12369960-12369960,hs2:12372645-12372645;hs2:40555062-40555062,hs2:78686837-78686837;hs2:63900644-63900644,hs2:176179133-176179133;hs2:63900646-63900646,hs2:176179119-176179119;hs2:78685414-78685414,hs2:40555062-40555062;hs2:102379496-102379496,hs2:109355974-109355974;hs2:172448061-172448061,hs2:173637622-173637622;hs2:172448061-172448061,hs2:173637622-173637622;hs2:176179132-176179132,hs2:63900634-63900634;hs2:186672954-186672954,hs2:186654331-186654331;hs3:3834568-3834568,hs3:3820326-3820326;hs3:121013940-121013940,hs3:121014043-121014043;hs3:122200142-122200142,hs3:122200197-122200197;hs4:72714689-72714689,hs22:50158256-50158256;hs4:132283261-132283261,hs4:132297084-132297084;hs4:144317983-144317983,hs4:144317891-144317891;hs5:35305661-35305661,hs10:114205128-114205128;hs7:40850149-40850149,hs7:41846253-41846253;hs7:40850149-40850149,hs7:41846253-41846253;hs8:10022420-10022420,hs8:135029870-135029870;hs8:19817022-19817022,hs8:3489795-3489795;hs8:32797612-32797612,hs8:33003443-33003443;hs8:32797615-32797615,hs8:32801119-32801119;hs8:33003449-33003449,hs8:52593586-52593586;hs8:33003553-33003553,hs8:32801124-32801124;hs8:33565022-33565022,hs8:42751079-42751079;hs8:33802316-33802316,hs8:41389673-41389673;hs8:33802606-33802606,hs8:42740151-42740151;hs8:33938890-33938890,hs8:38383664-38383664;hs8:34363629-34363629,hs8:40439288-40439288;hs8:34738487-34738487,hs8:41349058-41349058;hs8:35152145-35152145,hs8:40457135-40457135;hs8:35425128-35425128,hs8:43030916-43030916;hs8:35425132-35425132,hs8:43030916-43030916;hs8:35518102-35518102,hs8:38726593-38726593;hs8:36018492-36018492,hs8:43491062-43491062;hs8:36092475-36092475,hs8:40439881-40439881;hs8:36905668-36905668,hs8:39138168-39138168;hs8:37962219-37962219,hs8:42650011-42650011;hs8:38383468-38383468,hs8:39137712-39137712;hs8:38406501-38406501,hs8:39434675-39434675;hs8:39005932-39005932,hs8:42750641-42750641;hs8:40456981-40456981,hs8:35518290-35518290;hs8:41690105-41690105,hs8:33940233-33940233;hs8:41981041-41981041,hs8:42053399-42053399;hs8:42717762-42717762,hs8:42590038-42590038;hs8:42820001-42820001,hs8:40131819-40131819;hs8:43030477-43030477,hs8:43098475-43098475;hs8:47009554-47009554,hs8:110862767-110862767;hs8:76083913-76083913,hs8:78682752-78682752;hs8:78220523-78220523,hs8:78124580-78124580;hs8:80126508-80126508,hs8:80039302-80039302;hs8:83233679-83233679,hs8:117921027-117921027;hs8:85916753-85916753,hs8:89436223-89436223;hs8:104500556-104500556,hs8:106574934-106574934;hs8:104715306-104715306,hs8:10039759-10039759;hs8:110321690-110321690,hs8:114907572-114907572;hs8:113323346-113323346,hs8:113333495-113333495;hs8:114367382-114367382,hs8:115137397-115137397;hs8:117072421-117072421,hs8:116982986-116982986;hs8:137590138-137590138,hs8:139591703-139591703;hs10:59924521-59924521,hs10:59929757-59929757;hs10:59929863-59929863,hs10:59934682-59934682;hs10:59930284-59930284,hs10:59928967-59928967;hs10:59930284-59930284,hs10:59928967-59928967;hs10:77810044-77810044,hs10:78522769-78522769;hs10:77810044-77810044,hs10:78522769-78522769;hs10:77810044-77810044,hs10:78522769-78522769;hs10:88402703-88402703,hs10:32507525-32507525;hs12:23542591-23542591,hs14:88593733-88593733;hs12:38953236-38953236,hs12:21529818-21529818;hs17:35499733-35499733,hs17:35617124-35617124;hs19:36686497-36686497,hs10:11230133-11230133;hs20:60521456-60521456,hs20:60520564-60520564;hs23:144263583-144263583,hs23:144472906-144472906 FGFR1; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. GRCh37/hg19 Yes ADAM32,RNF170;C8orf86,ADAM32;RIMS2,MSRA CTDB0414 Research 25719666 Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grutzmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA; Australian Pancreatic Cancer Genome Initiative, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, Grimmond SM Whole genomes redefine the mutational landscape of pancreatic cancer Nature 2015 Feb 3 Pancreatic cancer Next Generation Sequencing Homo sapiens ICGC_0059 Illumina HiSeq 2000 chr10:0-127389287:0;chr10:127389288-128439429:-1;chr10:128439430-135534747:0;chr11:0-135006516:0;chr12:0-25872245:0;chr12:25872246-34414441:-1;chr12:34414442-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-21334777:0;chr2:21334778-22001683:-1;chr2:217915725-217993867:-1;chr2:217993868-243199373:0;chr2:22001684-217915724:0;chr3:0-78131967:0;chr3:118877415-80820129:1;chr3:172220462-171989369:1;chr3:172429136-172412681:1;chr3:172476665-82780298:1;chr3:190045000-190048756:-1;chr3:190113509-198022430:0;chr3:78131968-118881483:-1;chr3:83014922-82821204:1;chr3:83114349-190113508:-1;chr4:0-94332899:0;chr4:126686846-127536820:-1;chr4:127536821-140683203:0;chr4:140683204-153459905:-1;chr4:153459906-191154276:0;chr4:94332900-94857806:-1;chr4:94857807-126686845:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-146364022:0;chr9:0-9301697:0;chr9:9301698-9304495:-1;chr9:9304496-9458671:0;chr9:9458672-9684823:-1;chr9:9684824-141213431:0;chrX:0-102271590:0;chrX:102271591-102805328:-1;chrX:102805329-155270560:0;chrY:0-59373566:0 hs1:64103531-64103531,hs1:64023910-64023910;hs1:64850193-64850193,hs10:101600019-101600019;hs1:195973597-195973597,hs1:195973710-195973710;hs1:233962189-233962189,hs1:233963570-233963570;hs2:49854729-49854729,hs2:49864604-49864604;hs2:49862912-49862912,hs2:49872200-49872200;hs2:49865156-49865156,hs2:49865297-49865297;hs2:49865285-49865285,hs2:49872459-49872459;hs2:49867360-49867360,hs2:49860931-49860931;hs2:49872466-49872466,hs2:49865156-49865156;hs2:65859142-65859142,hs2:65858353-65858353;hs2:91937048-91937048,hs12:123873688-123873688;hs3:71415647-71415647,hs3:71413720-71413720;hs3:80971636-80971636,hs3:88407861-88407861;hs3:82817946-82817946,hs3:82828356-82828356;hs3:82830567-82830567,hs3:83015805-83015805;hs3:103627503-103627503,hs3:176341661-176341661;hs3:109924632-109924632,hs3:118615145-118615145;hs3:171997544-171997544,hs3:172384802-172384802;hs3:172072843-172072843,hs3:172238199-172238199;hs3:172235616-172235616,hs3:172438821-172438821;hs3:172385039-172385039,hs3:172433676-172433676;hs3:172475562-172475562,hs3:190530068-190530068;hs3:176538679-176538679,hs3:178048958-178048958;hs3:178952270-178952270,hs3:177916024-177916024;hs4:81239840-81239840,hs8:107752651-107752651;hs5:28652072-28652072,hs14:55618593-55618593;hs5:175733376-175733376,hs18:55381811-55381811;hs6:159046794-159046794,hs6:158969449-158969449;hs7:46595607-46595607,hs7:46595695-46595695;hs8:100916474-100916474,hs8:100895469-100895469;hs10:90368359-90368359,hs10:90368699-90368699;hs10:122628942-122628942,hs18:57150108-57150108;hs12:25660742-25660742,hs12:25130148-25130148;hs12:27023810-27023810,hs12:28180373-28180373;hs12:28103905-28103905,hs12:28211218-28211218;hs12:33211553-33211553,hs12:30979763-30979763;hs13:75213414-75213414,hs14:55618883-55618883;hs13:111852488-111852488,hs13:112019145-112019145;hs14:55618496-55618496,hs14:55618780-55618780;hs14:55618740-55618740,hs6:66526378-66526378;hs14:75581765-75581765,hs14:75581818-75581818;hs15:48101016-48101016,hs15:48101268-48101268;hs17:50197629-50197629,hs12:81391487-81391487;hs17:60807430-60807430,hs17:60807294-60807294;hs19:816668-816668,hs19:816426-816426;hs24:16975482-16975482,hs17:57707528-57707528 BZW1P1;CCT6P4;CLDN16;GCNT1P3;GHSR;NCEH1;SLC31A1P1;TNFSF10; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. GRCh37/hg19 Yes FNDC3B,NCEH1;FNDC3B,TNFSF10 CTDB0415 Research 25719666 Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grutzmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA; Australian Pancreatic Cancer Genome Initiative, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, Grimmond SM Whole genomes redefine the mutational landscape of pancreatic cancer Nature 2015 Feb 15 Pancreatic cancer Next Generation Sequencing Homo sapiens ICGC_0069 Illumina HiSeq 2000 chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-74903578:0;chr15:62553529-88218199:0;chr15:74903579-62553528:1;chr15:81504848-102531392:0;chr15:88218200-81504847:1;chr16:0-6733751:0;chr16:6733752-6746153:-1;chr16:6746154-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-18719933:0;chr4:18719934-18734248:-1;chr4:18734249-191154276:0;chr5:0-17603583:0;chr5:17603377-180915260:0;chr5:17603584-17603376:1;chr6:0-171115067:0;chr7:0-44105123:0;chr7:44105124-55782353:-1;chr7:55782354-159138663:0;chr8:0-52122989:0;chr8:111320246-146364022:0;chr8:52122990-52558645:-1;chr8:52130274-55083438:-1;chr8:55080109-52128202:1;chr8:55083439-75672293:0;chr8:75672294-111320245:-1;chr9:0-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs1:142787688-142787688,hs15:96397373-96397373;hs1:187947763-187947763,hs1:187954812-187954812;hs1:187947874-187947874,hs1:187982378-187982378;hs1:211502242-211502242,hs1:211502184-211502184;hs1:227467579-227467579,hs1:227473100-227473100;hs1:231607793-231607793,hsX:48977124-48977124;hs2:199710953-199710953,hs2:199713112-199713112;hs3:37718635-37718635,hs11:33288559-33288559;hs4:92925961-92925961,hs4:92873309-92873309;hs5:20547860-20547860,hs14:58706090-58706090;hs5:158687077-158687077,hs6:36247111-36247111;hs6:64769003-64769003,hs6:64768847-64768847;hs6:146323409-146323409,hs6:146298596-146298596;hs7:139819169-139819169,hs9:33002774-33002774;hs7:140173603-140173603,hs7:140143717-140143717;hs8:60467589-60467589,hs8:139995367-139995367;hs8:90023956-90023956,hs8:90023845-90023845;hs8:113825306-113825306,hs8:113825791-113825791;hs8:118508994-118508994,hs8:144025317-144025317;hs8:118509173-118509173,hs8:144025398-144025398;hs8:131988002-131988002,hs8:131988363-131988363;hs8:133124731-133124731,hs8:133115405-133115405;hs8:139995354-139995354,hs8:60470377-60470377;hs9:9145661-9145661,hs9:9178310-9178310;hs9:22043338-22043338,hs9:22126816-22126816;hs9:77543231-77543231,hs14:36281163-36281163;hs10:35640895-35640895,hs10:31753837-31753837;hs10:38115409-38115409,hsX:36047768-36047768;hs10:53679561-53679561,hs10:53679308-53679308;hs10:127948245-127948245,hs10:127948104-127948104;hs11:33342098-33342098,hs3:37617555-37617555;hs12:15370630-15370630,hs4:44547855-44547855;hs14:36117834-36117834,hs14:36119384-36119384;hs14:36266813-36266813,hs14:36267359-36267359;hs15:60193482-60193482,hs15:61077249-61077249;hs15:62809305-62809305,hs15:77985573-77985573;hs15:63895421-63895421,hs15:70393108-70393108;hs15:67977261-67977261,hs15:79859530-79859530;hs15:73776062-73776062,hs15:77985774-77985774;hs15:73777897-73777897,hs15:88462273-88462273;hs15:74903299-74903299,hs15:81506142-81506142;hs15:74903835-74903835,hs15:84689610-84689610;hs15:75247135-75247135,hs15:75274351-75274351;hs15:76701227-76701227,hs15:81784703-81784703;hs15:81505406-81505406,hs15:81506956-81506956;hs15:82016551-82016551,hs15:82142753-82142753;hs15:83786247-83786247,hs15:81783495-81783495;hs15:85885730-85885730,hs15:96290030-96290030;hs15:86069395-86069395,hs15:95884178-95884178;hs15:87493382-87493382,hs15:82146848-82146848;hs15:87501351-87501351,hs15:82127312-82127312;hs15:95843285-95843285,hs15:95843736-95843736;hs15:95877591-95877591,hs1:142798913-142798913;hs15:96310320-96310320,hs15:96440775-96440775;hs15:96429613-96429613,hs15:96518482-96518482;hs16:1339821-1339821,hs16:1339966-1339966;hs17:21548442-21548442,hs20:26079438-26079438;hs17:41110532-41110532,hs11:118225545-118225545;hs17:55291966-55291966,hs17:55281492-55281492;hs17:80583762-80583762,hs17:80592511-80592511;hs17:80604418-80604418,hs14:33002460-33002460;hs18:53870184-53870184,hs18:53839900-53839900;hs19:42002896-42002896,hs17:21726667-21726667;hs20:21770031-21770031,hs20:23883452-23883452;hs20:22543146-22543146,hs20:24109800-24109800;hs20:22545819-22545819,hs20:24109799-24109799;hs20:24108704-24108704,hs20:24108764-24108764;hs20:24123371-24123371,hs20:22542678-22542678;hs22:45334390-45334390,hs22:45336237-45336237;hsX:22672575-22672575,hsX:22672930-22672930;hsX:145181974-145181974,hsX:145167812-145167812 AKAP13;BTBD1;HMGN1P26;KLHL25; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. GRCh37/hg19 Yes C15orf60,LINGO1 CTDB0416 Research 25719666 Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grutzmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA; Australian Pancreatic Cancer Genome Initiative, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, Grimmond SM Whole genomes redefine the mutational landscape of pancreatic cancer Nature 2015 Feb 14 Pancreatic cancer Next Generation Sequencing Homo sapiens ICGC_0131 Illumina HiSeq 2000 chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-30736165:0;chr14:30717638-32201370:0;chr14:30736166-30717637:1;chr14:32201371-50990242:-1;chr14:32240974-31010651:1;chr14:32931626-76186652:-1;chr14:37060590-87020375:0;chr14:39493660-32300903:1;chr14:41277629-77774897:0;chr14:46710304-37983249:1;chr14:46710339-107349540:0;chr14:47617843-46350387:1;chr14:50886218-36399382:1;chr14:76186653-76661699:0;chr14:76450454-78505173:0;chr14:76661700-41277628:1;chr14:77585522-78515648:0;chr14:77774898-76450453:1;chr14:78505174-77585521:1;chr14:78515649-37060589:1;chr14:87020376-46710338:1;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-11049112:0;chr17:11049113-11049360:-1;chr17:11049361-43688024:0;chr17:43688025-45520025:-1;chr17:45520026-81195210:0;chr18:0-78077248:0;chr19:0-1062883:0;chr19:1062884-1248605:-1;chr19:1248606-50292185:0;chr19:50292186-50366076:-1;chr19:50366077-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-14745280:0;chr6:14745281-14745698:-1;chr6:14745699-171115067:0;chr7:0-61829245:0;chr7:110601757-110691241:-1;chr7:110691242-159138663:0;chr7:61829246-61829354:-1;chr7:61829355-110601756:0;chr8:0-3583336:0;chr8:3583337-3597576:-1;chr8:3597577-43444523:0;chr8:41138999-146364022:0;chr8:43444524-43448041:-1;chr8:43448042-43536332:0;chr8:43536333-41138998:1;chr9:0-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs1:11954514-11954514,hs21:39050074-39050074;hs1:178716640-178716640,hs1:178716693-178716693;hs2:80222459-80222459,hs2:80222650-80222650;hs2:86640837-86640837,hs2:86640892-86640892;hs2:131969113-131969113,hs6:11809179-11809179;hs2:140049049-140049049,hs2:140049479-140049479;hs2:161931745-161931745,hs2:161931253-161931253;hs3:59999981-59999981,hs3:61096854-61096854;hs3:146002981-146002981,hs3:146003064-146003064;hs3:151146128-151146128,hs18:65405909-65405909;hs3:151146520-151146520,hs18:65405921-65405921;hs4:19521427-19521427,hs4:19522043-19522043;hs4:57279732-57279732,hs4:57279631-57279631;hs4:91192146-91192146,hs4:91169877-91169877;hs4:91222774-91222774,hs4:91171457-91171457;hs4:117913141-117913141,hs4:117919231-117919231;hs4:130170961-130170961,hs14:79739674-79739674;hs4:160534224-160534224,hs4:160453026-160453026;hs4:174788390-174788390,hs4:174789046-174789046;hs5:45664516-45664516,hs2:147020927-147020927;hs5:140563527-140563527,hs5:140573649-140573649;hs6:529086-529086,hs6:528889-528889;hs6:3635254-3635254,hs9:21981015-21981015;hs6:27277783-27277783,hs6:27315562-27315562;hs6:28795495-28795495,hs6:28797390-28797390;hs6:30009588-30009588,hs6:30009687-30009687;hs6:30009588-30009588,hs6:30009687-30009687;hs6:69092656-69092656,hs22:29066425-29066425;hs6:137032520-137032520,hs6:137001570-137001570;hs6:165799869-165799869,hs6:165800027-165800027;hs7:6122062-6122062,hs13:26816255-26816255;hs7:56156974-56156974,hs7:56157331-56157331;hs7:56405153-56405153,hs7:56405505-56405505;hs7:84425628-84425628,hs7:84425682-84425682;hs7:90827334-90827334,hs7:90839050-90839050;hs8:37734921-37734921,hs8:43565999-43565999;hs8:41145404-41145404,hs20:26174848-26174848;hs8:41145407-41145407,hs20:26214817-26214817;hs8:43500445-43500445,hs8:43526143-43526143;hs9:73897323-73897323,hs9:73896989-73896989;hs9:96668254-96668254,hs9:96668330-96668330;hs10:77788790-77788790,hs14:74666901-74666901;hs10:101587566-101587566,hs8:140475594-140475594;hs11:13023333-13023333,hs18:53590744-53590744;hs14:19494321-19494321,hs19:19632149-19632149;hs14:21053497-21053497,hs14:20347986-20347986;hs14:21230084-21230084,hs14:21230288-21230288;hs14:21230253-21230253,hs14:22308469-22308469;hs14:23065372-23065372,hs14:36139860-36139860;hs14:29255148-29255148,hs14:49317840-49317840;hs14:29297657-29297657,hs14:48427020-48427020;hs14:29299826-29299826,hs14:48418411-48418411;hs14:29299914-29299914,hs14:29300177-29300177;hs14:31207400-31207400,hs14:34780066-34780066;hs14:31792425-31792425,hs14:77571384-77571384;hs14:31924403-31924403,hs14:32887898-32887898;hs14:32031755-32031755,hs14:53401721-53401721;hs14:32081588-32081588,hs14:78337991-78337991;hs14:32234403-32234403,hs14:78505185-78505185;hs14:32234554-32234554,hs14:37989959-37989959;hs14:32540107-32540107,hs14:78787608-78787608;hs14:36667226-36667226,hs14:53258916-53258916;hs14:37061176-37061176,hs14:46365854-46365854;hs14:39658225-39658225,hs14:45789061-45789061;hs14:40512548-40512548,hs14:39070240-39070240;hs14:44019855-44019855,hs14:50098927-50098927;hs14:46365654-46365654,hs14:87019882-87019882;hs14:48426422-48426422,hs14:87018854-87018854;hs14:49319884-49319884,hs22:46335540-46335540;hs14:53584736-53584736,hs14:76627967-76627967;hs14:54580071-54580071,hs14:76435482-76435482;hs14:63028197-63028197,hs13:98223904-98223904;hs14:74941307-74941307,hs14:77124207-77124207;hs14:75009783-75009783,hs14:54277712-54277712;hs14:75437756-75437756,hs14:75423484-75423484;hs14:76615806-76615806,hs14:77715188-77715188;hs14:76859227-76859227,hs14:78506179-78506179;hs14:77234985-77234985,hs14:77319561-77319561;hs14:77676832-77676832,hs14:88358037-88358037;hs14:77887374-77887374,hs14:86551780-86551780;hs14:78249717-78249717,hs14:78250208-78250208;hs14:78505502-78505502,hs14:87019472-87019472;hs14:88358034-88358034,hs14:72952921-72952921;hs14:106813931-106813931,hs14:106814760-106814760;hs15:20106601-20106601,hs15:20106665-20106665;hs15:30127612-30127612,hs15:30100605-30100605;hs15:51569450-51569450,hs15:51569601-51569601;hs15:74778904-74778904,hs15:74923611-74923611;hs17:26252860-26252860,hs17:41376874-41376874;hs17:26846669-26846669,hs17:26848927-26848927;hs17:26849170-26849170,hs17:37769728-37769728;hs17:26864246-26864246,hs17:80378758-80378758;hs17:26866035-26866035,hs17:61981595-61981595;hs17:27322757-27322757,hs17:58210234-58210234;hs17:27323697-27323697,hs17:80329037-80329037;hs17:36024323-36024323,hs17:40996155-40996155;hs17:36049132-36049132,hs17:80330608-80330608;hs17:37372138-37372138,hs17:40998803-40998803;hs17:37373211-37373211,hs17:40198293-40198293;hs17:40143259-40143259,hs17:41364138-41364138;hs17:40145402-40145402,hs17:80332278-80332278;hs17:40621840-40621840,hs17:41374562-41374562;hs17:40622334-40622334,hs17:73537478-73537478;hs17:41024036-41024036,hs17:41024136-41024136;hs17:41430509-41430509,hs17:58224027-58224027;hs17:43205641-43205641,hs17:43212078-43212078;hs17:43637655-43637655,hs17:43644554-43644554;hs17:43637665-43637665,hs17:43644449-43644449;hs17:46224160-46224160,hs17:58226044-58226044;hs17:46529425-46529425,hs17:62084488-62084488;hs17:48016598-48016598,hs17:36027667-36027667;hs17:58225045-58225045,hs17:73588404-73588404;hs17:61988018-61988018,hs17:40147827-40147827;hs17:62083458-62083458,hs17:73535878-73535878;hs17:80328730-80328730,hs17:80379064-80379064;hs18:20657881-20657881,hs18:20659634-20659634;hs19:40615761-40615761,hs2:65138905-65138905;hs20:26163239-26163239,hs20:26222143-26222143;hs20:26213566-26213566,hs20:26221817-26221817;hs21:11054622-11054622,hs24:59027440-59027440;hs22:29065554-29065554,hs22:29066001-29066001;hs22:29066021-29066021,hs6:69092643-69092643;hs23:121135127-121135127,hs23:121378138-121378138;hs23:121376636-121376636,hs23:121378167-121378167 ADCK1;AHSA1;ALKBH1;ANGEL1;AP4S1;ARF6;ARHGAP42P4;ARHGAP42P5;ATP5S;BAZ1A;C14orf166B;C14orf178;C14orf182;C14orf183;C14orf28;CFL2;CLEC14A;DNAAF2;DPPA3P2;DTD2;EAPP;ERO1L;FAM177A1;FAM179B;FANCM;FCF1;FERMT2;FKBP3;FKSG61;FSCB;G2E3;GEMIN2;GNPNAT1;GPR137C;GPR33;GSTZ1;HEATR5A;HECTD1;HIGD1AP17;IFT43;IGBP1P1;INSM2;IRF2BPL;ISCA2;ISM2;KLHDC1;KLHDC2;KLHL28;KRT18P6;KRT8P2;L2HGDH;LRFN5;LTBP2;MBIP;MDGA2;METTL21D;MGAT2;MIPOL1;MIS18BP1;NEMF;NF1P4;NFKBIA;NGB;NKX2-1;NKX2-8;NOXRED1;NPC2;NUBPL;OR11H12;OR11H13P;OR11H2;OR11K2P;OR4H12P;OR4K1;OR4K16P;OR4K2;OR4K3;OR4K5;OR4K6P;OR4M1;OR4N2;OR4Q3;PAX9;PHKBP2;PNN;POLE2;POTEG;POTEM;PPP2R3C;PRKD1;PRPF39;PSMA6;PSMC6;PTCSC3;QRSL1P3;RAP1AP;RHOQP1;RN7SL1;RN7SL2;RNA5SP384;RNA5SP388;RPA2P;RPL10L;RPL13AP2;RPL21P10;RPL21P5;RPL29P3;RPL32P29;RPL36AL;RPS15AP3;RPS19P3;RPS29;RPS3AP4;SAMD15;SEC23A;SLIRP;SNW1;SNX6;SOS2;SPTLC2;SPTSSA;SRP54;SSTR1;STYX;TGFB3;TMED8;TMEM63C;TRAPPC6B;UBE2CP1;VASH1;ZDHHC22; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. GRCh37/hg19 Yes AKAP6,TTLL5;DDHD1,GPATCH2L;DTD2,AKAP6;HEATR5A,KIAA1737;NUBPL,ADCK1;NUBPL,FERMT2;RP11-176H8.1,AKAP6 CTDB0417 Research 25719666 Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grutzmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA; Australian Pancreatic Cancer Genome Initiative, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, Grimmond SM Whole genomes redefine the mutational landscape of pancreatic cancer Nature 2015 Feb 18 Pancreatic cancer Next Generation Sequencing Homo sapiens ICGC_0154 Illumina HiSeq 2000 chr10:0-135534747:0;chr11:0-62647962:0;chr11:62647963-64550175:-1;chr11:64550176-79066110:0;chr11:68853851-135006516:0;chr11:79066111-68853850:1;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-10268628:0;chr18:10268629-11260768:-1;chr18:11260769-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-15979994:0;chr21:15979995-16139697:-1;chr21:16139698-39214982:0;chr21:39214983-47284002:-1;chr21:47284003-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-109860790:0;chr8:109860791-126920998:-1;chr8:126920999-126934938:0;chr8:126934939-127099671:-1;chr8:127099672-146364022:0;chr9:0-21842702:0;chr9:21842703-22047656:-1;chr9:22047657-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs1:192749594-192749594,hs6:18869815-18869815;hs4:18830687-18830687,hs4:18830763-18830763;hs4:41072750-41072750,hs4:41074456-41074456;hs4:190559871-190559871,hs18:58850148-58850148;hs5:21567041-21567041,hs5:33501106-33501106;hs5:24545507-24545507,hs22:42599855-42599855;hs5:113247176-113247176,hs19:24587974-24587974;hs5:113496069-113496069,hs22:25955548-25955548;hs6:75534095-75534095,hs21:11054315-11054315;hs8:10093410-10093410,hs8:10096202-10096202;hs8:42224568-42224568,hs5:40520773-40520773;hs8:95279094-95279094,hs22:47422451-47422451;hs8:95279591-95279591,hs22:47422075-47422075;hs8:95280341-95280341,hs22:40476239-40476239;hs8:107283500-107283500,hs8:112852147-112852147;hs8:107380443-107380443,hs8:106650799-106650799;hs8:108926849-108926849,hs8:107283570-107283570;hs8:109063583-109063583,hs8:109064538-109064538;hs8:109897015-109897015,hs8:110355271-110355271;hs8:111611664-111611664,hs8:111612482-111612482;hs8:111611664-111611664,hs8:111612482-111612482;hs8:111901730-111901730,hs8:111901818-111901818;hs8:111929739-111929739,hs8:108890548-108890548;hs8:115756851-115756851,hs8:121073502-121073502;hs8:118348670-118348670,hs8:118793307-118793307;hs8:119321539-119321539,hs8:119322723-119322723;hs8:126914696-126914696,hs8:130646395-130646395;hs8:127085791-127085791,hs8:130606405-130606405;hs8:130606060-130606060,hs8:126914532-126914532;hs9:19090081-19090081,hs9:19089825-19089825;hs11:77917875-77917875,hs11:81682531-81682531;hs11:81638858-81638858,hs11:81291300-81291300;hs11:81681062-81681062,hs11:81686570-81686570;hs12:33538777-33538777,hs12:39769603-39769603;hs12:38852808-38852808,hs12:39666732-39666732;hs14:58472424-58472424,hs23:11732036-11732036;hs18:5700895-5700895,hs18:43447835-43447835;hs18:6067752-6067752,hs18:67162206-67162206;hs18:6086302-6086302,hs18:58826878-58826878;hs18:6540031-6540031,hs18:54121994-54121994;hs18:8329567-8329567,hs18:33486002-33486002;hs18:8383800-8383800,hs18:54129354-54129354;hs18:11356902-11356902,hs18:67197176-67197176;hs18:18643142-18643142,hs18:40066128-40066128;hs18:22339305-22339305,hs18:22352839-22352839;hs18:26119477-26119477,hs21:18541134-18541134;hs18:33262431-33262431,hs21:19652837-19652837;hs18:35173973-35173973,hs18:54128946-54128946;hs18:35193393-35193393,hs18:44309448-44309448;hs18:40076857-40076857,hs18:13650258-13650258;hs18:58785908-58785908,hs21:15886805-15886805;hs18:58839106-58839106,hs21:18551324-18551324;hs18:60998180-60998180,hs18:30824859-30824859;hs18:62158707-62158707,hs18:57207252-57207252;hs18:67189037-67189037,hs18:8230489-8230489;hs18:76777013-76777013,hs18:76774346-76774346;hs18:76854054-76854054,hs21:28861248-28861248;hs19:56817730-56817730,hs19:56818508-56818508;hs20:25760369-25760369,hs22:24724822-24724822;hs21:26530221-26530221,hs21:47030004-47030004;hs21:30692690-30692690,hs21:10932393-10932393;hs21:31558887-31558887,hs18:60996277-60996277;hs21:47052950-47052950,hs18:24416200-24416200;hs22:17312856-17312856,hs22:40481905-40481905;hs22:17399026-17399026,hs22:17920312-17920312;hs22:17404618-17404618,hs22:19692098-19692098;hs22:21808336-21808336,hs22:21947710-21947710;hs22:21959775-21959775,hs22:23068182-23068182;hs22:42073403-42073403,hs22:42087567-42087567;hs22:42567363-42567363,hs22:42568119-42568119;hs22:44488406-44488406,hs22:44489267-44489267;hs23:44763368-44763368,hs23:44810110-44810110;hs23:96640614-96640614,hs23:96729973-96729973 GATA6; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. GRCh37/hg19 Yes DOK6,PTPRM;GALNT1,TMPRSS15;KDSR,CCDC178;L3MBTL4,DOK6 CTDB0418 Research 25719666 Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grutzmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA; Australian Pancreatic Cancer Genome Initiative, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, Grimmond SM Whole genomes redefine the mutational landscape of pancreatic cancer Nature 2015 Feb 2 Pancreatic cancer Next Generation Sequencing Homo sapiens ICGC_0214 Illumina HiSeq 2000 chr10:0-135534747:0;chr11:0-119409357:0;chr11:119409358-121844570:-1;chr11:121844571-135006516:0;chr12:0-127125217:0;chr12:127125218-132439257:-1;chr12:132439258-133851895:0;chr13:0-68241965:0;chr13:68241966-68442104:-1;chr13:68442105-115169878:0;chr14:0-96764158:0;chr14:96764159-99909140:-1;chr14:99909141-107349540:0;chr15:0-53253126:0;chr15:53253127-53501579:-1;chr15:53501580-102531392:0;chr16:0-90354753:0;chr17:0-36478131:0;chr17:36478132-36589895:-1;chr17:36589896-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-208107973:0;chr1:208107974-211175919:-1;chr1:208152650-239097446:-1;chr1:222282392-223680506:-1;chr1:239097447-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-48506967:0;chr22:48506968-49490605:-1;chr22:49490606-51304566:0;chr2:0-1697686:0;chr2:10294062-31552803:-1;chr2:12839903-62521000:0;chr2:14063960-12830974:1;chr2:1697687-62432705:-1;chr2:187572610-214630222:-1;chr2:212020336-230672819:-1;chr2:21435895-38882340:-1;chr2:215089492-215379706:-1;chr2:228249417-187541922:1;chr2:230672820-243199373:0;chr2:31332429-50570836:-1;chr2:31467783-14539980:1;chr2:32256664-32006062:1;chr2:32257480-31925814:1;chr2:32257891-31280645:1;chr2:50379350-50787189:-1;chr2:50379468-187572609:0;chr2:50773133-31325607:1;chr2:50784676-31330005:1;chr2:5841029-5962887:-1;chr2:62432706-62515749:0;chr2:62515750-12839902:1;chr2:62521001-50379467:1;chr3:0-198022430:0;chr4:0-29301965:0;chr4:29301966-29439843:-1;chr4:29439844-191154276:0;chr5:0-98391003:0;chr5:126975307-147852753:-1;chr5:147852754-149690416:0;chr5:149690417-150021960:-1;chr5:150021961-178191019:0;chr5:178191020-178563198:-1;chr5:178563199-180915260:0;chr5:98391004-98622669:-1;chr5:98622670-126975306:0;chr6:0-30780582:0;chr6:30780583-42078753:-1;chr6:42078754-63030194:0;chr6:63030195-63082410:-1;chr6:63082411-91372726:0;chr6:91372727-92099239:-1;chr6:92099240-171115067:0;chr7:0-159138663:0;chr8:0-146364022:0;chr9:0-141213431:0;chrX:0-146317987:0;chrX:146317988-146407684:-1;chrX:146407685-155270560:0;chrY:0-59373566:0 hs1:5717255-5717255,hs1:5784943-5784943;hs1:18433773-18433773,hs17:20748484-20748484;hs1:33858332-33858332,hs4:134852961-134852961;hs1:33858992-33858992,hs1:33859200-33859200;hs1:95598150-95598150,hs1:95922554-95922554;hs1:194764181-194764181,hs3:82867204-82867204;hs1:195403345-195403345,hs3:82854527-82854527;hs1:198481499-198481499,hs1:235656702-235656702;hs1:207995417-207995417,hs1:197009922-197009922;hs1:208108313-208108313,hs1:210988829-210988829;hs1:208158003-208158003,hs1:210991302-210991302;hs2:1473521-1473521,hs2:32257511-32257511;hs2:1677908-1677908,hs2:1718126-1718126;hs2:1678180-1678180,hs2:1923223-1923223;hs2:1687429-1687429,hs2:19671991-19671991;hs2:1690645-1690645,hs2:2355010-2355010;hs2:2220363-2220363,hs2:62447579-62447579;hs2:2220866-2220866,hs2:10416764-10416764;hs2:10275859-10275859,hs2:12897822-12897822;hs2:10404593-10404593,hs2:31291697-31291697;hs2:10404675-10404675,hs2:32589121-32589121;hs2:10423966-10423966,hs2:50385877-50385877;hs2:10431389-10431389,hs2:10580090-10580090;hs2:10555355-10555355,hs2:50509573-50509573;hs2:10557950-10557950,hs2:32277366-32277366;hs2:10558314-10558314,hs2:50382799-50382799;hs2:10558846-10558846,hs2:31810915-31810915;hs2:10575182-10575182,hs2:32274963-32274963;hs2:12830853-12830853,hs2:31450925-31450925;hs2:12839031-12839031,hs2:62095558-62095558;hs2:12843959-12843959,hs2:14277300-14277300;hs2:12875236-12875236,hs2:13673400-13673400;hs2:12880638-12880638,hs2:31941785-31941785;hs2:12927979-12927979,hs2:14540410-14540410;hs2:13043730-13043730,hs2:13678298-13678298;hs2:13049970-13049970,hs2:32277948-32277948;hs2:13054125-13054125,hs2:50381612-50381612;hs2:13054174-13054174,hs2:32105652-32105652;hs2:13059394-13059394,hs2:32003987-32003987;hs2:13064377-13064377,hs2:50719869-50719869;hs2:14273262-14273262,hs2:31997500-31997500;hs2:14273616-14273616,hs2:50879654-50879654;hs2:14275793-14275793,hs2:50815622-50815622;hs2:15314088-15314088,hs2:31520989-31520989;hs2:20753800-20753800,hs2:26136663-26136663;hs2:20760115-20760115,hs2:22217476-22217476;hs2:22226425-22226425,hs2:26130857-26130857;hs2:22227860-22227860,hs2:26140242-26140242;hs2:31279431-31279431,hs2:11991066-11991066;hs2:31281412-31281412,hs2:50350172-50350172;hs2:31291618-31291618,hs2:10424306-10424306;hs2:31325499-31325499,hs2:32576943-32576943;hs2:31329878-31329878,hs2:13678581-13678581;hs2:31455284-31455284,hs2:50773194-50773194;hs2:31520980-31520980,hs2:14545245-14545245;hs2:31521358-31521358,hs2:50884063-50884063;hs2:31552821-31552821,hs2:32576237-32576237;hs2:31553352-31553352,hs2:31289933-31289933;hs2:31806441-31806441,hs2:62474053-62474053;hs2:31809295-31809295,hs2:31956680-31956680;hs2:31810503-31810503,hs2:62519596-62519596;hs2:31934861-31934861,hs2:62218751-62218751;hs2:31996866-31996866,hs2:50350233-50350233;hs2:32082790-32082790,hs2:32288111-32288111;hs2:32106343-32106343,hs2:12928028-12928028;hs2:32256928-32256928,hs2:61997633-61997633;hs2:32287985-32287985,hs2:50510411-50510411;hs2:32294407-32294407,hs2:12889743-12889743;hs2:32353375-32353375,hs2:50715314-50715314;hs2:36336832-36336832,hs2:76714378-76714378;hs2:38881050-38881050,hs2:20744810-20744810;hs2:50351460-50351460,hs2:31467964-31467964;hs2:50363081-50363081,hs2:31956775-31956775;hs2:50374199-50374199,hs2:31881446-31881446;hs2:50381583-50381583,hs2:50368418-50368418;hs2:50382679-50382679,hs2:12897933-12897933;hs2:50449514-50449514,hs2:50720780-50720780;hs2:50637186-50637186,hs2:50713227-50713227;hs2:50638608-50638608,hs2:62468569-62468569;hs2:50748785-50748785,hs2:50877145-50877145;hs2:50815561-50815561,hs2:32350874-32350874;hs2:50817530-50817530,hs2:62221978-62221978;hs2:50883768-50883768,hs2:62455634-62455634;hs2:61898625-61898625,hs2:10429522-10429522;hs2:61995220-61995220,hs2:32274765-32274765;hs2:62095499-62095499,hs2:61898732-61898732;hs2:62102647-62102647,hs2:50374819-50374819;hs2:62222315-62222315,hs2:62216763-62216763;hs2:62447063-62447063,hs2:50360135-50360135;hs2:62448464-62448464,hs2:50879725-50879725;hs2:62468957-62468957,hs2:31552113-31552113;hs2:76714376-76714376,hs4:27196180-27196180;hs2:76726550-76726550,hs2:187515092-187515092;hs2:173915570-173915570,hs2:194419547-194419547;hs2:187509505-187509505,hs2:210283413-210283413;hs2:187512357-187512357,hs2:213721435-213721435;hs2:187515051-187515051,hs2:36336883-36336883;hs2:187539624-187539624,hs2:228229672-228229672;hs2:187543895-187543895,hs2:187535010-187535010;hs2:187543910-187543910,hs2:228242487-228242487;hs2:188207987-188207987,hs2:189031038-189031038;hs2:188809917-188809917,hs2:216833040-216833040;hs2:189025152-189025152,hs2:214963170-214963170;hs2:189073741-189073741,hs2:212020548-212020548;hs2:190337052-190337052,hs4:127469716-127469716;hs2:190957617-190957617,hs2:190957949-190957949;hs2:190957959-190957959,hs2:214707891-214707891;hs2:193761105-193761105,hs2:174192749-174192749;hs2:213561077-213561077,hs2:214677481-214677481;hs2:214672886-214672886,hs2:188080842-188080842;hs2:214707939-214707939,hs2:192942281-192942281;hs2:216822318-216822318,hs2:191118755-191118755;hs2:216822345-216822345,hs2:216822738-216822738;hs2:228228893-228228893,hs2:228229665-228229665;hs2:228238261-228238261,hs2:214131359-214131359;hs3:47844481-47844481,hs3:47807028-47807028;hs3:178112111-178112111,hs3:178112513-178112513;hs4:27190750-27190750,hs6:24704719-24704719;hs4:27190809-27190809,hs6:24704720-24704720;hs4:27196144-27196144,hs6:16969400-16969400;hs4:30225236-30225236,hs4:30914850-30914850;hs4:77735511-77735511,hs4:77753445-77753445;hs4:86419604-86419604,hs4:87159277-87159277;hs4:87401076-87401076,hs4:87404865-87404865;hs4:91899126-91899126,hs4:91905853-91905853;hs4:96619339-96619339,hs4:96792252-96792252;hs4:117003496-117003496,hs4:138817358-138817358;hs4:117007412-117007412,hs4:77736728-77736728;hs4:126336308-126336308,hs4:162014215-162014215;hs4:134853242-134853242,hs1:33859139-33859139;hs4:135962205-135962205,hs4:115387888-115387888;hs4:162008311-162008311,hs4:162008681-162008681;hs5:150077741-150077741,hs5:150077956-150077956;hs5:157184643-157184643,hs8:140680656-140680656;hs6:24708515-24708515,hs2:76726606-76726606;hs6:30134142-30134142,hs6:103269017-103269017;hs6:30142271-30142271,hs6:30144999-30144999;hs6:31233533-31233533,hs6:106586941-106586941;hs6:41667173-41667173,hs6:98645291-98645291;hs6:57475909-57475909,hs19:23220465-23220465;hs6:76957319-76957319,hs6:92511239-92511239;hs6:78241163-78241163,hs6:92704244-92704244;hs7:102480478-102480478,hs7:127900792-127900792;hs7:103359043-103359043,hs7:128317781-128317781;hs7:157825833-157825833,hs7:157825893-157825893;hs8:304610-304610,hs9:36535180-36535180;hs8:1243515-1243515,hs4:84183858-84183858;hs8:1619901-1619901,hs9:18786347-18786347;hs8:140438213-140438213,hs13:85375221-85375221;hs9:20684140-20684140,hs9:32665001-32665001;hs9:21929548-21929548,hs9:21930878-21930878;hs9:21930001-21930001,hs9:23734185-23734185;hs9:27330229-27330229,hs9:32665048-32665048;hs9:35905729-35905729,hs9:35905819-35905819;hs10:82702819-82702819,hs10:83331533-83331533;hs10:83324216-83324216,hs10:110544123-110544123;hs11:20963637-20963637,hs11:20963730-20963730;hs11:119409307-119409307,hs11:119409359-119409359;hs11:132047598-132047598,hs11:132866328-132866328;hs11:132049795-132049795,hs11:132072694-132072694;hs11:132072596-132072596,hs11:132125799-132125799;hs11:132087118-132087118,hs11:132124003-132124003;hs11:132087201-132087201,hs11:132159837-132159837;hs12:41767811-41767811,hs12:41769189-41769189;hs12:41769874-41769874,hs11:119420858-119420858;hs12:127644076-127644076,hs12:127644137-127644137;hs13:71122720-71122720,hs13:71122805-71122805;hs13:84687705-84687705,hs5:158350714-158350714;hs13:115103781-115103781,hs13:115104402-115104402;hs14:36403024-36403024,hs14:36404765-36404765;hs14:106217114-106217114,hs14:106315327-106315327;hs15:98762034-98762034,hs15:98762369-98762369;hs17:30917114-30917114,hs17:39303272-39303272;hs17:35628376-35628376,hs17:35631015-35631015;hs17:39707208-39707208,hs20:34975253-34975253;hs17:48760464-48760464,hs20:12935118-12935118;hs20:34953263-34953263,hs20:34954960-34954960;hs22:48428556-48428556,hs22:48428721-48428721;hs23:31455136-31455136,hs23:32385887-32385887;hs23:68764724-68764724,hs2:124651616-124651616;hs23:68766113-68766113,hs23:68866391-68866391;hs23:77580270-77580270,hs23:77800638-77800638;hs23:78199893-78199893,hs23:78200448-78200448;hs23:98103899-98103899,hs23:144304403-144304403;hs23:102744799-102744799,hs23:144291914-144291914;hs23:102825032-102825032,hs23:122165455-122165455;hs23:122143065-122143065,hs23:153199462-153199462;hs23:144247547-144247547,hs23:153723917-153723917;hs23:144247714-144247714,hs23:154466372-154466372;hs23:144260306-144260306,hs23:144242091-144242091;hs23:148148091-148148091,hs23:148147703-148147703;hs23:153212911-153212911,hs23:153709970-153709970 CIR1;HOXD10;HOXD11;HOXD12;HOXD13;HOXD9;SCRN3; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. GRCh37/hg19 Yes C2orf88,SPAG16;CCT4,NRXN1;DPY30,GALNT14;FAM171B,SPAG16;GALNT14,NRXN1;HPCAL1,NRXN1;ITGAV,TM4SF20;MREG,HIBCH;MYT1L,B3GNT2;NRXN1,GALNT14;SPAG16,VWC2L;SPAST,NRXN1;TPO,DPY30 CTDB0419 Research 25719666 Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grutzmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA; Australian Pancreatic Cancer Genome Initiative, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, Grimmond SM Whole genomes redefine the mutational landscape of pancreatic cancer Nature 2015 Feb 15 Pancreatic cancer Next Generation Sequencing Homo sapiens ICGC_0242 Illumina HiSeq 2000 chr10:0-83677439:0;chr10:83677440-83993433:-1;chr10:83993434-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-24015124:0;chr15:24015125-24019302:-1;chr15:24019303-25234380:0;chr15:25234381-84031593:-1;chr15:25438273-94740245:-1;chr15:28215971-28219152:-1;chr15:94740246-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-105893411:0;chr1:105893412-105893532:-1;chr1:105893533-249250621:0;chr20:0-63025520:0;chr21:0-11121763:0;chr21:11121764-11130259:-1;chr21:11130260-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-42831559:0;chr3:103697747-198022430:0;chr3:103720395-103697746:1;chr3:42831560-66481263:-1;chr3:60425664-60427126:-1;chr3:66481264-103720394:0;chr4:0-137134729:0;chr4:137134730-137138118:-1;chr4:137138119-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-64245079:0;chr7:107512123-76040784:1;chr7:107676297-159138663:0;chr7:64245080-69414325:-1;chr7:69414326-76038334:0;chr7:76038335-107676296:-1;chr7:76041976-68169942:1;chr7:80850077-81213827:-1;chr8:0-81130493:0;chr8:81130494-81131443:-1;chr8:81131444-146364022:0;chr9:0-7210195:0;chr9:7210196-7210633:-1;chr9:7210634-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs1:117384844-117384844,hs1:117384777-117384777;hs1:120603720-120603720,hs1:120603591-120603591;hs1:149858214-149858214,hs1:149818151-149818151;hs1:218158248-218158248,hs1:218122840-218122840;hs1:246056323-246056323,hs1:246012028-246012028;hs2:11902837-11902837,hs2:11855181-11855181;hs2:60807404-60807404,hs2:60811687-60811687;hs2:60811536-60811536,hs2:60839859-60839859;hs2:101854561-101854561,hs2:101811284-101811284;hs2:174999623-174999623,hs2:174996895-174996895;hs2:181881108-181881108,hs2:181857808-181857808;hs2:193759771-193759771,hs2:193652545-193652545;hs2:195947791-195947791,hs2:195915537-195915537;hs2:204683460-204683460,hs2:204685171-204685171;hs2:208614784-208614784,hs2:208626111-208626111;hs2:208688103-208688103,hs2:208607411-208607411;hs2:234580982-234580982,hs2:234444869-234444869;hs3:47714610-47714610,hs3:47668365-47668365;hs3:81764449-81764449,hs3:81711619-81711619;hs3:88684295-88684295,hs3:88701566-88701566;hs3:88701106-88701106,hs3:88704281-88704281;hs3:106682233-106682233,hs3:106655286-106655286;hs3:110126528-110126528,hs3:110131405-110131405;hs3:110130732-110130732,hs3:110139586-110139586;hs3:116491223-116491223,hs3:116457131-116457131;hs3:116550903-116550903,hs3:116809391-116809391;hs3:170231654-170231654,hs3:170231503-170231503;hs3:174513956-174513956,hs3:174507396-174507396;hs3:175486846-175486846,hs3:175482720-175482720;hs4:18799-18799,hs4:191034022-191034022;hs4:24154925-24154925,hs4:24130380-24130380;hs4:133256150-133256150,hs4:133251378-133251378;hs4:191042352-191042352,hs15:40493080-40493080;hs5:11233276-11233276,hs5:11172452-11172452;hs5:136056618-136056618,hs5:136026092-136026092;hs5:179681482-179681482,hs5:179611720-179611720;hs6:8320580-8320580,hs6:44423199-44423199;hs6:10356405-10356405,hs6:10346713-10346713;hs6:20684219-20684219,hs6:44256981-44256981;hs6:40145563-40145563,hs6:40146918-40146918;hs6:50075469-50075469,hs6:50053681-50053681;hs6:169008548-169008548,hs6:169008460-169008460;hs7:8190915-8190915,hs7:8190862-8190862;hs7:28050835-28050835,hs7:28052410-28052410;hs7:28054629-28054629,hs7:28054869-28054869;hs7:28089326-28089326,hs7:28042996-28042996;hs7:68169139-68169139,hs23:64126024-64126024;hs7:68173671-68173671,hs7:76977289-76977289;hs7:70907446-70907446,hs7:76978056-76978056;hs7:71065850-71065850,hs23:8715825-8715825;hs7:71080181-71080181,hs7:107553891-107553891;hs7:76976273-76976273,hs23:57007690-57007690;hs7:80877376-80877376,hs7:80961799-80961799;hs7:80961995-80961995,hs7:81214376-81214376;hs7:106860301-106860301,hs7:107512583-107512583;hs7:107202170-107202170,hs23:56844976-56844976;hs7:108539773-108539773,hs23:64568051-64568051;hs7:109775375-109775375,hs23:9861435-9861435;hs7:110252583-110252583,hs23:9859576-9859576;hs7:125433572-125433572,hs7:125433888-125433888;hs7:125438029-125438029,hs7:125371388-125371388;hs7:133832518-133832518,hs7:133866002-133866002;hs7:151084996-151084996,hs7:151038374-151038374;hs8:3615089-3615089,hs8:3617067-3617067;hs8:3616934-3616934,hs8:3629563-3629563;hs8:3618478-3618478,hs8:3619453-3619453;hs8:3618693-3618693,hs8:3620311-3620311;hs8:3628698-3628698,hs8:3634307-3634307;hs8:49115924-49115924,hs8:49058935-49058935;hs8:61458505-61458505,hs8:61487845-61487845;hs8:61483122-61483122,hs8:61490494-61490494;hs8:81153027-81153027,hs6:21291589-21291589;hs8:101425725-101425725,hs8:101436386-101436386;hs8:101429035-101429035,hs8:101436069-101436069;hs8:101468965-101468965,hs8:101429357-101429357;hs8:101719225-101719225,hs8:101721361-101721361;hs9:21964433-21964433,hs9:21969775-21969775;hs9:21964438-21964438,hs9:22450624-22450624;hs9:70988414-70988414,hs9:70959068-70959068;hs9:88565290-88565290,hs9:88544343-88544343;hs9:88574650-88574650,hs9:88565808-88565808;hs10:68939011-68939011,hs10:68876425-68876425;hs10:127190418-127190418,hs10:127201102-127201102;hs11:46478179-46478179,hs20:36970978-36970978;hs11:46574648-46574648,hs20:37332339-37332339;hs11:47247149-47247149,hs11:47252206-47252206;hs11:47263385-47263385,hs11:47242267-47242267;hs11:90933269-90933269,hs11:90903254-90903254;hs11:123418542-123418542,hs11:123375151-123375151;hs11:129164383-129164383,hs11:129151036-129151036;hs12:40670712-40670712,hs15:78765739-78765739;hs12:40671176-40671176,hs12:40672995-40672995;hs12:41532584-41532584,hs12:57502165-57502165;hs12:56626009-56626009,hs15:24421755-24421755;hs12:84951214-84951214,hs12:84926395-84926395;hs13:37053864-37053864,hs13:37054224-37054224;hs14:45644353-45644353,hs14:45644409-45644409;hs14:76292628-76292628,hs14:76297161-76297161;hs14:76292740-76292740,hs14:76300466-76300466;hs14:103532863-103532863,hs14:103488764-103488764;hs15:22529102-22529102,hs15:24007274-24007274;hs15:22687197-22687197,hs15:81447212-81447212;hs15:22689010-22689010,hs15:81077740-81077740;hs15:24292144-24292144,hs15:25272130-25272130;hs15:25229267-25229267,hs15:94373139-94373139;hs15:25265905-25265905,hs15:25278542-25278542;hs15:25274425-25274425,hs15:25282962-25282962;hs15:25296658-25296658,hs15:94619541-94619541;hs15:25297005-25297005,hs15:86283368-86283368;hs15:26500331-26500331,hs12:56269546-56269546;hs15:30753998-30753998,hs15:82045054-82045054;hs15:32016356-32016356,hs15:96344139-96344139;hs15:32066508-32066508,hs15:85495765-85495765;hs15:32097996-32097996,hs15:97210695-97210695;hs15:32098018-32098018,hs15:32099904-32099904;hs15:32098884-32098884,hs15:32103588-32103588;hs15:32976590-32976590,hs15:95360595-95360595;hs15:81075481-81075481,hs15:97176088-97176088;hs15:81445142-81445142,hs15:97208050-97208050;hs15:83730144-83730144,hs15:100094401-100094401;hs15:85497153-85497153,hs15:91992841-91992841;hs15:85638350-85638350,hs15:32068322-32068322;hs15:85639994-85639994,hs15:97177926-97177926;hs15:87814948-87814948,hs15:98606268-98606268;hs15:88003519-88003519,hs15:93902787-93902787;hs15:88851691-88851691,hs15:25430415-25430415;hs15:88853305-88853305,hs15:101218956-101218956;hs15:92899398-92899398,hs15:25272976-25272976;hs15:93236607-93236607,hs15:82046538-82046538;hs15:94617152-94617152,hs15:92901693-92901693;hs15:97214504-97214504,hs15:97200549-97200549;hs15:97323212-97323212,hs15:97325713-97325713;hs15:98062142-98062142,hs15:101216594-101216594;hs15:98063036-98063036,hs15:100095163-100095163;hs15:101239052-101239052,hs15:25238191-25238191;hs16:821542-821542,hs16:720720-720720;hs16:17429107-17429107,hs16:17403329-17403329;hs16:25919164-25919164,hs16:25921546-25921546;hs16:67699521-67699521,hs16:67666424-67666424;hs18:48580061-48580061,hs18:48565899-48565899;hs18:58006341-58006341,hs18:57991424-57991424;hs19:808924-808924,hs19:795248-795248;hs19:49212513-49212513,hs19:49440152-49440152;hs20:14286590-14286590,hs20:14211136-14211136;hs20:18674153-18674153,hs20:18658049-18658049;hs21:11022750-11022750,hs22:45991519-45991519;hs22:26869564-26869564,hs22:26820313-26820313;hs23:9859755-9859755,hs7:106924421-106924421;hs23:23428526-23428526,hs23:23440494-23440494;hs23:23441793-23441793,hs23:23443376-23443376;hs23:37426057-37426057,hs23:63826416-63826416;hs23:47527028-47527028,hs23:47510067-47510067;hs23:52642070-52642070,hs23:48140773-48140773;hs23:61787502-61787502,hs23:61785259-61785259;hs23:63647735-63647735,hs7:66839500-66839500;hs23:81909288-81909288,hs23:81840808-81840808;hs23:90476182-90476182,hs23:90477415-90477415;hs23:103785622-103785622,hs23:103790542-103790542;hs23:103785723-103785723,hs23:103790570-103790570;hs23:103790347-103790347,hs23:103818984-103818984;hs23:122616552-122616552,hs23:122560526-122560526 ABHD2;ACAN;ADAMTS17;ADAMTS7;ADAMTSL3;AEN;AGPHD1;AKAP13;ALDH1A3;ALPK3;ANKRD34C;ANP32BP3;ANPEP;AP3B2;AP3S2;AP4E1;ARNT2;ARRDC4;ASB7;BCL2A1;BTBD1;C15orf26;C15orf32;C15orf37;C15orf38;C15orf40;C2CD4A;CERS3;CHRNA3;CHRNA5;CHRNA7;CHRNB4;CHSY1;CIB1;CPEB1;CRTC3;CSPG4P5;CTSH;DET1;DKFZP779J2370;DNM1P31;DNM1P32;DNM1P38;DNM1P42;DNM1P44;DNM1P46;EFTUD1;EFTUD1P1;EGLN1P1;ENO1P2;FAH;FAM103A1;FAM108C1;FAM149B1P1;FAM154B;FAM169B;FANCI;FSD2;GABARAPL3;GDPGP1;GOLGA6L10;GOLGA6L3;GOLGA6L5;GOLGA6L9;GOLGA8K;GOLGA8N;GOLGA8O;HAPLN3;HMGB1P8;HOMER2;HSP90B2P;IDH2;IGF1R;IL16;IQGAP1;IREB2;ISG20;KIAA1024;KIAA1199;KIF7;LINS;LRRC28;LRRK1;LYSMD4;MCTP2;MEF2A;MESDC1;MESDC2;MESP1;MESP2;MEX3B;MFGE8;MIR1469;MORF4L1;MRPL15P1;MRPL46;MRPS11;MTHFS;NGRN;NMB;NPAP1;NR2F2;NTRK3;OR4F13P;OR4F15;OR4F6;OTUD7A;PCSK6;PDE8A;PEX11A;PGAM1P12;PGPEP1L;PLIN1;POLG;PRKXP1;PSMA4;PWRN1;PWRN2;RASGRF1;RHCG;RLBP1;RNA5SP401;RNA5SP402;RPL18P11;RPL21P116;RPL36AP43;RPL7P5;RPL9P8;RPL9P9;RPS12P26;RPS17;RPS17L;RPS27L;SCAND2;SCG5;SEC11A;SEMA4B;SH3GL3;SLC28A1;SLCO3A1;SNHG14;SNRPA1;SNRPN;SNURF;SPATA8;ST20;ST8SIA2;STARD5;SYNM;TARSL2;TICRR;TM2D3;TMC3;TMED3;TTC23;TTLL13;UBE2Q2P1;UBE2Q2P2;UBE2Q2P3;ULK4P1;VIMP;VPS13C;WDR73;WDR93;WHAMM;ZFAND6;ZNF592;ZNF710;ZNF774;ZSCAN2; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. GRCh37/hg19 Yes BTBD1,MEF2A;OTUD7A,SLC28A1 CTDB0420 Research 25719666 Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grutzmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA; Australian Pancreatic Cancer Genome Initiative, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, Grimmond SM Whole genomes redefine the mutational landscape of pancreatic cancer Nature 2015 Feb 14 Pancreatic cancer Next Generation Sequencing Homo sapiens ICGC_0285 Illumina HiSeq 2000 chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-115169878:0;chr14:0-22748346:0;chr14:22748347-70039551:-1;chr14:28806200-33253161:-1;chr14:46359233-70177736:-1;chr14:61969520-88787111:-1;chr14:76557977-79122197:-1;chr14:88787112-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-58346598:0;chr2:58346599-58391370:-1;chr2:58391371-243199373:0;chr3:0-60320947:0;chr3:60320948-60590043:-1;chr3:60464067-60587666:-1;chr3:60590044-198022430:0;chr4:0-118436189:0;chr4:118436190-118877701:-1;chr4:118877702-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-146364022:0;chr9:0-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs1:15028823-15028823,hs11:75631514-75631514;hs1:115389342-115389342,hs1:115389430-115389430;hs1:142674675-142674675,hs4:49220939-49220939;hs2:130822609-130822609,hs2:130823277-130823277;hs2:240217012-240217012,hs17:36169343-36169343;hs3:60665998-60665998,hs3:60668750-60668750;hs3:73630866-73630866,hs3:73630782-73630782;hs6:25361937-25361937,hs6:25462390-25462390;hs6:163814221-163814221,hs8:75184915-75184915;hs7:16963033-16963033,hs7:16848770-16848770;hs7:76144766-76144766,hs7:76648272-76648272;hs7:100875539-100875539,hs12:7032418-7032418;hs8:119222600-119222600,hs12:3072473-3072473;hs8:131734707-131734707,hs13:113037519-113037519;hs8:139754789-139754789,hs8:139754514-139754514;hs10:47621515-47621515,hs10:47683110-47683110;hs11:130835147-130835147,hsX:11732700-11732700;hs11:130835585-130835585,hsX:11731377-11731377;hs12:503368-503368,hs12:506384-506384;hs12:2136299-2136299,hs12:2137198-2137198;hs12:2136302-2136302,hs12:2137072-2137072;hs12:4914054-4914054,hs12:4916494-4916494;hs12:5056660-5056660,hs12:5058136-5058136;hs12:7027858-7027858,hs12:7032386-7032386;hs12:14863361-14863361,hs12:73102548-73102548;hs13:49533344-49533344,hs13:49536625-49536625;hs13:90904631-90904631,hs13:90905841-90905841;hs14:20567119-20567119,hs14:70765261-70765261;hs14:20570529-20570529,hs14:104201816-104201816;hs14:25911556-25911556,hs14:25939492-25939492;hs14:25939239-25939239,hs14:25952440-25952440;hs14:28946711-28946711,hs14:89795007-89795007;hs14:28991980-28991980,hs14:60785597-60785597;hs14:37754429-37754429,hs14:70765870-70765870;hs14:47474391-47474391,hs14:93673586-93673586;hs14:50832570-50832570,hs14:79121478-79121478;hs14:53308020-53308020,hs14:47475441-47475441;hs14:55933286-55933286,hs14:75180469-75180469;hs14:59459822-59459822,hs14:77493487-77493487;hs14:60729531-60729531,hs14:83807231-83807231;hs14:70177409-70177409,hs14:90423041-90423041;hs14:73101069-73101069,hs14:97720809-97720809;hs14:75180523-75180523,hs14:75181867-75181867;hs14:75690551-75690551,hs14:75691743-75691743;hs14:76113998-76113998,hs16:31205301-31205301;hs14:76558319-76558319,hs14:91152317-91152317;hs14:77491801-77491801,hs14:25304825-25304825;hs14:79541771-79541771,hs14:79546183-79546183;hs14:79566785-79566785,hs14:79568348-79568348;hs14:79566820-79566820,hs14:79568791-79568791;hs14:79569115-79569115,hs14:87262838-87262838;hs14:83897092-83897092,hs14:96836537-96836537;hs14:91148147-91148147,hs14:28806596-28806596;hs14:91148148-91148148,hs14:28806715-28806715;hs14:96083512-96083512,hs14:96083457-96083457;hs14:96258975-96258975,hs14:28947810-28947810;hs14:97718173-97718173,hs14:45813125-45813125;hs14:99381415-99381415,hs14:61367574-61367574;hs15:24853619-24853619,hs15:24865097-24865097;hs15:72389131-72389131,hs22:41726727-41726727;hs15:72396048-72396048,hs22:30936193-30936193;hs15:93389841-93389841,hs15:93340422-93340422;hs16:24353297-24353297,hs16:24354566-24354566;hs16:33952705-33952705,hs16:33953695-33953695;hs16:78910362-78910362,hs16:78917807-78917807;hs17:3802553-3802553,hs1:242227150-242227150;hs17:27224031-27224031,hs17:43351838-43351838;hs17:43349269-43349269,hs17:46700561-46700561;hs19:30574825-30574825,hs11:74975891-74975891;hs20:14547529-14547529,hs20:14549049-14549049;hs20:35020897-35020897,hs20:35020993-35020993;hs22:37355133-37355133,hs3:140910140-140910140;hs22:43549345-43549345,hs22:43549653-43549653;hs22:47211171-47211171,hs22:47211234-47211234 Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. GRCh37/hg19 Yes CDKL1,NRXN3;IRF2BPL,STXBP6;KIAA0247,TDP1;MDGA2,RP11-371E8.4;MDGA2,UBR7 CTDB0421 Research 25719666 Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grutzmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA; Australian Pancreatic Cancer Genome Initiative, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, Grimmond SM Whole genomes redefine the mutational landscape of pancreatic cancer Nature 2015 Feb 1 Pancreatic cancer Next Generation Sequencing Homo sapiens ICGC_0300 Illumina HiSeq 2000 chr10:0-24861537:0;chr10:24861538-32060125:-1;chr10:31962055-36634117:-1;chr10:36634118-135534747:0;chr11:0-135006516:0;chr12:0-133851895:0;chr13:0-23519126:0;chr13:23519127-27784262:-1;chr13:27784263-35147450:0;chr13:35147451-46013185:-1;chr13:35148053-115169878:0;chr13:35555829-33276227:1;chr13:46013186-46067163:0;chr13:46067164-35148052:1;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-81195210:0;chr18:0-78077248:0;chr19:0-59128983:0;chr1:0-16448880:0;chr1:146953171-147013988:-1;chr1:147013989-161043318:0;chr1:161043319-162812008:-1;chr1:162812009-164707019:0;chr1:16448881-16825689:-1;chr1:164707020-223309227:-1;chr1:16825690-43752712:0;chr1:170186635-201274599:-1;chr1:171432473-227249607:-1;chr1:174989280-172994699:1;chr1:180354551-179035249:1;chr1:180634533-234997230:-1;chr1:180634660-249250621:0;chr1:180636656-180634185:1;chr1:180639580-189302029:-1;chr1:229653882-238186131:-1;chr1:238186132-238187955:0;chr1:238187956-180634659:1;chr1:43752713-44196704:-1;chr1:44196705-146953170:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-66252186:0;chr4:66252187-66691404:-1;chr4:66691405-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-146364022:0;chr9:0-20973150:0;chr9:20973151-32231383:-1;chr9:27384096-28104309:-1;chr9:28386112-32637207:-1;chr9:32637208-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs1:44629872-44629872,hs1:145211144-145211144;hs1:46416637-46416637,hs1:236773470-236773470;hs1:120679380-120679380,hs12:93771899-93771899;hs1:151236474-151236474,hs1:151295285-151295285;hs1:153158652-153158652,hs1:190789771-190789771;hs1:165970033-165970033,hs1:234537355-234537355;hs1:171270695-171270695,hs1:239139224-239139224;hs1:172344237-172344237,hs1:175298952-175298952;hs1:175270747-175270747,hs1:176846371-176846371;hs1:176849248-176849248,hs1:176850451-176850451;hs1:180634124-180634124,hs1:234818350-234818350;hs1:180638958-180638958,hs1:229653506-229653506;hs1:186942630-186942630,hs1:234701944-234701944;hs1:186942893-186942893,hs1:191110727-191110727;hs1:190789608-190789608,hs1:190789758-190789758;hs1:200506286-200506286,hs1:208027250-208027250;hs1:206872695-206872695,hs1:207695080-207695080;hs1:223131595-223131595,hs1:171273271-171273271;hs1:225952133-225952133,hs1:171343521-171343521;hs1:229650108-229650108,hs1:41444007-41444007;hs1:231951031-231951031,hs1:218857562-218857562;hs1:234668836-234668836,hs1:240774472-240774472;hs1:242100869-242100869,hs1:31670934-31670934;hs2:13428696-13428696,hs5:145554181-145554181;hs2:82557847-82557847,hs2:82561311-82561311;hs2:185744146-185744146,hs22:29065829-29065829;hs3:1062579-1062579,hs22:29065775-29065775;hs3:100577155-100577155,hs3:113784681-113784681;hs3:101386193-101386193,hs3:114341392-114341392;hs6:32592405-32592405,hs6:32592536-32592536;hs8:33978043-33978043,hs20:21232971-21232971;hs9:26383599-26383599,hs13:52612486-52612486;hs9:26663709-26663709,hs13:44214501-44214501;hs9:32983897-32983897,hs13:52822182-52822182;hs9:32983998-32983998,hs13:52822178-52822178;hs9:38433266-38433266,hs13:46780225-46780225;hs10:36599399-36599399,hs10:26670112-26670112;hs10:37118755-37118755,hs18:20361720-20361720;hs10:131039151-131039151,hs10:131039421-131039421;hs11:31034639-31034639,hs22:29066114-29066114;hs11:31034640-31034640,hs22:29065466-29065466;hs11:40954283-40954283,hs11:40954390-40954390;hs12:75485425-75485425,hs22:29065435-29065435;hs13:27875958-27875958,hs13:35562754-35562754;hs13:33282781-33282781,hs13:42327476-42327476;hs13:34193537-34193537,hs13:52774139-52774139;hs13:34266700-34266700,hs13:34857815-34857815;hs13:35200485-35200485,hs13:46009631-46009631;hs13:52154612-52154612,hs13:52154409-52154409;hs15:85706213-85706213,hs16:27705000-27705000;hs18:20486904-20486904,hs10:35315815-35315815;hs18:22097962-22097962,hs10:33020151-33020151;hs22:29065904-29065904,hs12:75485444-75485444;hs22:29066066-29066066,hs3:1062570-1062570;hs23:12468357-12468357,hs23:72594491-72594491;hs23:12553888-12553888,hs23:12555125-12555125;hs23:27228798-27228798,hs23:27229315-27229315;hs23:31308303-31308303,hs23:31020428-31020428 ACTA1;ACTBP11;ADAM15;ADAMTSL4;ADAR;AIM2;ANKRD34A;ANKRD35;ANKRD45;ANP32E;ANXA9;APCS;APH1A;APOA1BP;AQP10;ARF1;ARHGEF11;ARHGEF2;ARNT;ASH1L;ATP6V1E1P1;ATP8B2;AXDND1;BANF1P4;BCAN;BGLAP;BNIPL;BOLA1;BTNL10;C1orf110;C1orf138;C1orf145;C1orf148;C1orf189;C1orf35;C1orf43;C1orf51;C1orf54;C1orf56;C1orf61;C1orf85;CA14;CACYBP;CADM3;CAPN2;CCSAP;CCT3;CCT8P1;CD160;CD1A;CD1B;CD1C;CD1D;CD1E;CD5L;CDC42SE1;CENPL;CERS2;CHD1L;CHRNB2;CHTOP;CICP5;CKS1B;CLK2;CNIH4;COX5BP8;CRABP2;CREB3L4;CRP;CRPP1;CRTC2;CTSK;CTSS;CYCSP52;DAP3;DAP3P1;DARC;DARS2;DCST1;DCST2;DEGS1;DENND4B;DPM3;DRD5P2;DUSP5P1;ECM1;EFNA1;EFNA3;EFNA4;EIF4A1P11;ELL2P1;EMBP1;ENAH;ENSA;ETV3;ETV3L;FAM108A2;FAM108A3P;FAM63A;FAM72B;FAM72C;FAM91A2;FAM96AP2;FBXO28;FCER1A;FCGR1A;FCGR1B;FCGR1C;FCRL1;FCRL2;FCRL3;FCRL4;FCRL5;FDPS;FLAD1;FMO5;FTH1P2;GABPB2;GAS5;GBAP1;GJA8;GJC2;GM2AP2;GNRHR2;GON4L;GOT2P2;GPATCH4;GPR52;GPR89A;GPR89B;GPR89C;GUK1;HAPLN2;HAX1;HCN3;HDGF;HFE2;HIST2H2AA3;HIST2H2AA4;HIST2H2AB;HIST2H2AC;HIST2H2BA;HIST2H2BB;HIST2H2BC;HIST2H2BD;HIST2H2BE;HIST2H2BF;HIST2H3A;HIST2H3C;HIST2H3D;HIST2H3DP1;HIST2H3PS2;HIST2H4A;HIST2H4B;HIST3H2A;HIST3H2BA;HIST3H2BB;HIST3H3;HMGB3P6;HMGN1P5;HMGN2P18;HORMAD1;HYDIN2;IBA57;IFI16;IFRG15;IL6R;ILF2;INSRR;INTS3;IQGAP3;ISG20L2;ITGA10;JMJD4;JTB;KCNN3;KIRREL;KLHL20;KRT8P45;KRTCAP2;LAMTOR2;LBR;LENEP;LHX4;LIX1L;LMNA;LRRC71;MCL1;MEF2AP1;MEF2D;MEX3A;MLLT11;MNDA;MRPL24;MRPL55;MRPS14;MRPS21;MRPS21P2;MSTO1;MTMR11;MTX1;MTX1P1;MUC1;NBPF10;NBPF11;NBPF12;NBPF14;NBPF15;NBPF16;NBPF20;NBPF23;NBPF24;NES;NKAIN1P1;NOTCH2NL;NPHS2;NPR1;NTRK1;NUDT17;NUDT4P1;NUF2;NUP210L;NVL;OBSCN;OR10AA1P;OR10J1;OR10J2P;OR10J3;OR10J4;OR10J5;OR10J6P;OR10J7P;OR10J8P;OR10J9P;OR10K1;OR10K2;OR10R1P;OR10R2;OR10R3P;OR10T1P;OR10T2;OR10X1;OR10Z1;OR13Z1P;OR2AQ1P;OR6K1P;OR6K2;OR6K3;OR6K4P;OR6K5P;OR6K6;OR6N1;OR6N2;OR6P1;OR6Y1;OTUD7B;PAQR6;PBXIP1;PDIA3P;PDZK1;PDZK1P1;PDZK1P2;PEAR1;PEX11B;PFN1P12;PFN1P3;PFN1P4;PFN1P5;PFN1P6;PFN1P7;PFN1P8;PHBP11;PIAS3;PKLR;PLEKHO1;PMF1;PMVK;POLR3C;POLR3GL;POU5F1P4;PPIAL4A;PPIAL4C;PPIAL4D;PPIAL4E;PPIAL4F;PRCC;PRDX6;PRKAB2;PRPF3;PRSS38;PRUNE;PTPN2P1;PYGO2;PYHIN1;RAB13;RAB25;RAB4A;RABGAP1L-IT1;RBM8A;RC3H1;RFWD2;RGS4;RGS5;RHBG;RHOU;RIT1;RNA5S1;RNA5S10;RNA5S11;RNA5S12;RNA5S13;RNA5S14;RNA5S15;RNA5S16;RNA5S17;RNA5S2;RNA5S3;RNA5S4;RNA5S5;RNA5S6;RNA5S7;RNA5S8;RNA5S9;RNA5SP18;RNA5SP19;RNA5SP57;RNA5SP58;RNA5SP59;RNA5SP60;RNA5SP62;RNA5SP63;RNA5SP67;RNA5SP68;RNA5SP77;RNF115;RNF187;RPRD2;RPS27;RPS7P2;RRNAD1;RUSC1;RXFP4;S100A1;S100A13;S100A14;S100A16;S100A2;S100A3;S100A4;S100A5;S100A6;SCARNA3;SEC22B;SEMA4A;SERPINC1;SETDB1;SETP10;SF3B4;SH2D2A;SHC1;SHE;SLC25A44;SLC27A3;SLC39A1;SLC50A1;SMG5;SNAP47;SNAPIN;SOAT1;SPHAR;SPRR2A;SPRR2B;SPRR2C;SPRR2E;SPRR2F;SPRR2G;SPTA1;SRGAP2C;SSR2;SV2A;SYT11;TARS2;TDRD10;TDRD5;THBS3;TMEM78;TMEM79;TNFSF18;TNFSF4;TOR1AIP1;TOR3A;TP53BP2;TPM3;TRIM11;TRIM17;TRIM46;TSACC;TTC24;TXNIP;UBAP2L;UBE2D3P3;UBE2Q1;UBQLN4;VDAC1P9;VHLL;VPS45;WDR26;WNT3A;WNT9A;YY1AP1;ZBTB37;ZBTB7B;ZNF678;ZNF847P; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. GRCh37/hg19 Yes DNM3,TNR;MAPKAPK2,CR1;XPR1,ABCB10 CTDB0422 Research 25719666 Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grutzmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA; Australian Pancreatic Cancer Genome Initiative, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, Grimmond SM Whole genomes redefine the mutational landscape of pancreatic cancer Nature 2015 Feb 18 Pancreatic cancer Next Generation Sequencing Homo sapiens ICGC_0326 Illumina HiSeq 2000 chr10:0-135534747:0;chr11:0-135006516:0;chr12:0-128127609:0;chr12:117790616-133851895:0;chr12:128127610-117790615:1;chr13:0-115169878:0;chr14:0-107349540:0;chr15:0-102531392:0;chr16:0-90354753:0;chr17:0-79134247:0;chr17:79134248-79214069:-1;chr17:79214070-81195210:0;chr18:0-20697044:0;chr18:20681228-78077248:0;chr18:20697045-21046735:-1;chr18:20719999-22239764:-1;chr18:20732881-21406056:-1;chr18:20887353-25658851:-1;chr18:21414908-30397351:-1;chr18:22243538-30370126:-1;chr18:25632536-33728583:-1;chr18:25653477-35230964:-1;chr18:28401869-38193019:-1;chr18:33735244-20638703:1;chr18:33740209-20733068:1;chr18:38193020-75018808:0;chr18:75018809-20681227:1;chr19:0-59128983:0;chr1:0-249250621:0;chr20:0-63025520:0;chr21:0-48129895:0;chr22:0-51304566:0;chr2:0-243199373:0;chr3:0-198022430:0;chr4:0-191154276:0;chr5:0-180915260:0;chr6:0-171115067:0;chr7:0-159138663:0;chr8:0-146364022:0;chr9:0-14072345:0;chr9:14072346-22636514:-1;chr9:20510368-22994820:-1;chr9:22994821-27608641:0;chr9:27608642-34592116:-1;chr9:28008731-28173749:-1;chr9:34592117-141213431:0;chrX:0-155270560:0;chrY:0-59373566:0 hs2:54847169-54847169,hs19:7590836-7590836;hs3:129885829-129885829,hs4:9081729-9081729;hs3:174937457-174937457,hs3:175415198-175415198;hs4:53810-53810,hs18:21427413-21427413;hs4:10631567-10631567,hs11:7236366-7236366;hs4:69555074-69555074,hs17:79050328-79050328;hs4:113035328-113035328,hs4:113035254-113035254;hs4:134782520-134782520,hs4:134782375-134782375;hs5:17900859-17900859,hs11:101256794-101256794;hs5:46164109-46164109,hs5:46164440-46164440;hs5:114990579-114990579,hs5:114990653-114990653;hs6:29332294-29332294,hs6:29332596-29332596;hs7:69907547-69907547,hs7:69964700-69964700;hs7:90260231-90260231,hs13:97252597-97252597;hs9:69006947-69006947,hs9:69007000-69007000;hs9:101897142-101897142,hs9:101898952-101898952;hs11:101903472-101903472,hs5:164468879-164468879;hs12:68339430-68339430,hs12:68341279-68341279;hs12:68340568-68340568,hs12:68339929-68339929;hs12:68343433-68343433,hs12:68343786-68343786;hs12:69758688-69758688,hs12:69759079-69759079;hs12:69758688-69758688,hs12:69759079-69759079;hs12:73647739-73647739,hs12:117789872-117789872;hs12:73745584-73745584,hs12:117799233-117799233;hs12:73746388-73746388,hs12:111332021-111332021;hs12:73921918-73921918,hs12:90846317-90846317;hs12:76686883-76686883,hs12:126699944-126699944;hs12:111332528-111332528,hs12:117809273-117809273;hs12:111333499-111333499,hs12:127774324-127774324;hs12:112964664-112964664,hs15:87156445-87156445;hs12:114200447-114200447,hs12:114201706-114201706;hs12:114987615-114987615,hs12:114988503-114988503;hs12:117755004-117755004,hs12:117755581-117755581;hs12:117790000-117790000,hs12:128128138-128128138;hs12:117790477-117790477,hs12:90845657-90845657;hs12:117790510-117790510,hs12:117790961-117790961;hs12:126553969-126553969,hs12:128290870-128290870;hs12:126780558-126780558,hs15:87005783-87005783;hs17:30313708-30313708,hs17:30298564-30298564;hs17:79047868-79047868,hs17:79213515-79213515;hs17:79131869-79131869,hs17:79131919-79131919;hs17:79196200-79196200,hs17:79202843-79202843;hs17:79197281-79197281,hs4:69554919-69554919;hs17:79205201-79205201,hs17:79240391-79240391;hs17:79240113-79240113,hs17:79242305-79242305;hs17:79241381-79241381,hs17:79211948-79211948;hs18:14184199-14184199,hs18:14184304-14184304;hs18:20675454-20675454,hs4:52076-52076;hs18:20728913-20728913,hs20:2726372-2726372;hs18:20737560-20737560,hs18:21051200-21051200;hs18:20766669-20766669,hs18:30390118-30390118;hs18:20837847-20837847,hs18:38194838-38194838;hs18:20839309-20839309,hs18:29412406-29412406;hs18:20851132-20851132,hs18:20861023-20861023;hs18:20855382-20855382,hs18:33721335-33721335;hs18:20860679-20860679,hs18:33739194-33739194;hs18:20874050-20874050,hs18:37605772-37605772;hs18:21051072-21051072,hs20:2740178-2740178;hs18:21062083-21062083,hs18:35246182-35246182;hs18:21419721-21419721,hs18:29412626-29412626;hs18:21420215-21420215,hs20:2727045-2727045;hs18:22242856-22242856,hs18:29413131-29413131;hs18:22244047-22244047,hs18:75019000-75019000;hs18:22248527-22248527,hs20:2734612-2734612;hs18:22278409-22278409,hs20:15310884-15310884;hs18:24945149-24945149,hs18:20851798-20851798;hs18:25644475-25644475,hs18:29406344-29406344;hs18:29351939-29351939,hs18:30402921-30402921;hs18:29394121-29394121,hs18:35194427-35194427;hs18:29413322-29413322,hs18:74979776-74979776;hs18:29441240-29441240,hs18:20710291-20710291;hs18:30396881-30396881,hs18:20839771-20839771;hs18:33719460-33719460,hs18:75015039-75015039;hs18:33741177-33741177,hs18:33741370-33741370;hs18:38211746-38211746,hs18:75018543-75018543;hs18:38216053-38216053,hs18:29335634-29335634;hs18:74996219-74996219,hs18:22243121-22243121;hs18:75018454-75018454,hs18:33721579-33721579;hs19:6807280-6807280,hs19:6808621-6808621;hs19:7130220-7130220,hs19:7131734-7131734;hs19:58720136-58720136,hs19:58721041-58721041;hs19:58721058-58721058,hs19:58721270-58721270;hs20:20482581-20482581,hs20:23059829-23059829;hs20:23053857-23053857,hs20:23099475-23099475;hs20:23087477-23087477,hs20:23090028-23090028;hs20:29593601-29593601,hs20:29599334-29599334;hs21:16418269-16418269,hs21:17406126-17406126;hs21:16418269-16418269,hs21:17406126-17406126;hs21:27975131-27975131,hs21:26978205-26978205;hs21:41460081-41460081,hs21:41401622-41401622 ARIH2P1;CELF4;FHOD3;TPGS2; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. GRCh37/hg19 Yes CABLES1,LAMA3;CABLES1,TRAPPC8;ELP2,CABLES1;LAMA3,TRAPPC8;TMEM241,CDH2;TMEM241,ELP2;TRAPPC8,GALR1 CTDB0427 Research 26337081 Kovtun IV, Murphy SJ, Johnson SH, Cheville JC, Vasmatzis G Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer Oncotarget 2015 Oct 4 Prostate cancer Next Generation Sequencing Homo sapiens PR3 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA Massive genomic rearrangements, a result of single catastrophic event termed chromothrispsis or chromosomal catastrophe, have been identified in a variety of human cancers. In a few cancer types, chromothripsis was found to be associated with poor prognosis. We performed mate-pair sequencing and analysis of structural rearrangements in 132 prostate cancer cases which included clinically insignificant Gleason score 6 tumors, clinically significant tumors of higher grade (7+) and high grade prostatic intraepithelial neoplasia. Chromothripsis was observed at least 30 per cent of the samples across different grades. Surprisingly, it was frequently observed in clinically insignificant Gleason score 6 tumors, indicating that chromothripsis does not define more aggressive phenotype. The degree of chromothripsis did not increase significantly in tumors of advanced grades and did not appear to contribute to tumor progression. Our data showed that distribution of chromothriptic rearrangements differed from that of fragile sites but correlated with the size of chromosomes. We also provided evidence that rearrangements resulting from chromothripsis were present in the cells of neighboring Gleason patterns of the same tumor. Our data suggest that that chromothripsis plays role in prostate cancer initiation. GRCh37/hg19 Yes NA CTDB0428 Research 26337081 Kovtun IV, Murphy SJ, Johnson SH, Cheville JC, Vasmatzis G Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer Oncotarget 2015 Oct 5 Prostate cancer Next Generation Sequencing Homo sapiens PR119 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA Massive genomic rearrangements, a result of single catastrophic event termed chromothrispsis or chromosomal catastrophe, have been identified in a variety of human cancers. In a few cancer types, chromothripsis was found to be associated with poor prognosis. We performed mate-pair sequencing and analysis of structural rearrangements in 132 prostate cancer cases which included clinically insignificant Gleason score 6 tumors, clinically significant tumors of higher grade (7+) and high grade prostatic intraepithelial neoplasia. Chromothripsis was observed at least 30 per cent of the samples across different grades. Surprisingly, it was frequently observed in clinically insignificant Gleason score 6 tumors, indicating that chromothripsis does not define more aggressive phenotype. The degree of chromothripsis did not increase significantly in tumors of advanced grades and did not appear to contribute to tumor progression. Our data showed that distribution of chromothriptic rearrangements differed from that of fragile sites but correlated with the size of chromosomes. We also provided evidence that rearrangements resulting from chromothripsis were present in the cells of neighboring Gleason patterns of the same tumor. Our data suggest that that chromothripsis plays role in prostate cancer initiation. GRCh37/hg19 Yes NA CTDB0429 Research 26337081 Kovtun IV, Murphy SJ, Johnson SH, Cheville JC, Vasmatzis G Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer Oncotarget 2015 Oct 1 Prostate cancer Next Generation Sequencing Homo sapiens PR27 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA Massive genomic rearrangements, a result of single catastrophic event termed chromothrispsis or chromosomal catastrophe, have been identified in a variety of human cancers. In a few cancer types, chromothripsis was found to be associated with poor prognosis. We performed mate-pair sequencing and analysis of structural rearrangements in 132 prostate cancer cases which included clinically insignificant Gleason score 6 tumors, clinically significant tumors of higher grade (7+) and high grade prostatic intraepithelial neoplasia. Chromothripsis was observed at least 30 per cent of the samples across different grades. Surprisingly, it was frequently observed in clinically insignificant Gleason score 6 tumors, indicating that chromothripsis does not define more aggressive phenotype. The degree of chromothripsis did not increase significantly in tumors of advanced grades and did not appear to contribute to tumor progression. Our data showed that distribution of chromothriptic rearrangements differed from that of fragile sites but correlated with the size of chromosomes. We also provided evidence that rearrangements resulting from chromothripsis were present in the cells of neighboring Gleason patterns of the same tumor. Our data suggest that that chromothripsis plays role in prostate cancer initiation. GRCh37/hg19 Yes NA CTDB0430 Research 26337081 Kovtun IV, Murphy SJ, Johnson SH, Cheville JC, Vasmatzis G Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer Oncotarget 2015 Oct 2 Prostate cancer Next Generation Sequencing Homo sapiens PR64 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA Massive genomic rearrangements, a result of single catastrophic event termed chromothrispsis or chromosomal catastrophe, have been identified in a variety of human cancers. In a few cancer types, chromothripsis was found to be associated with poor prognosis. We performed mate-pair sequencing and analysis of structural rearrangements in 132 prostate cancer cases which included clinically insignificant Gleason score 6 tumors, clinically significant tumors of higher grade (7+) and high grade prostatic intraepithelial neoplasia. Chromothripsis was observed at least 30 per cent of the samples across different grades. Surprisingly, it was frequently observed in clinically insignificant Gleason score 6 tumors, indicating that chromothripsis does not define more aggressive phenotype. The degree of chromothripsis did not increase significantly in tumors of advanced grades and did not appear to contribute to tumor progression. Our data showed that distribution of chromothriptic rearrangements differed from that of fragile sites but correlated with the size of chromosomes. We also provided evidence that rearrangements resulting from chromothripsis were present in the cells of neighboring Gleason patterns of the same tumor. Our data suggest that that chromothripsis plays role in prostate cancer initiation. GRCh37/hg19 Yes NA CTDB0431 Research 26337081 Kovtun IV, Murphy SJ, Johnson SH, Cheville JC, Vasmatzis G Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer Oncotarget 2015 Oct 4 Prostate cancer Next Generation Sequencing Homo sapiens PR6 ANXA5;AP1AR;ARSJ;ATHGEF38;BANK1;BBS12;BBS7;BDH2;CAMK2D;CASP6;CCRN4L;CENPE;CFI;Col25A1;CXXC4;CYP2U1;DKK2;EGF;ELF2;ELMOD2;ELOVL5;ENPEP;EXOSC9;FABP2;FABPC4L;FAT4;FGF2;FLK4;FREM3;GAB1;GAR1;GSTCD;GYPA;GYPB;GYPE;HADH;LRIT3;MAD2L1;MAML3;MANBA;METL14;MFSD8;MGARP;MGST2;NAA15;NDNF;NDST4;NDUFC1;NEUROG2;NFKB;NPNT;NUDT6;OSTC;OTUD4;PAPSS2;PCDH18;PDE5A;PGRMC;PHF17;PITX2;PLA2G12A;PRDM5;PRSS12;QRFPR;RAB33B;RNF150;RPL34;RRH;SCL1T;SCOC;SEC24B;SEC24D;SETD7;SPRY1;SYNPO2;TACR3;TBC1D9;TBCK;TET2;TIFA;TMEM155;TNIP3;TRAM1L1;TRPC3;UBE2D3;UCP1;UGT8;USP38;USP53 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA Massive genomic rearrangements, a result of single catastrophic event termed chromothrispsis or chromosomal catastrophe, have been identified in a variety of human cancers. In a few cancer types, chromothripsis was found to be associated with poor prognosis. We performed mate-pair sequencing and analysis of structural rearrangements in 132 prostate cancer cases which included clinically insignificant Gleason score 6 tumors, clinically significant tumors of higher grade (7+) and high grade prostatic intraepithelial neoplasia. Chromothripsis was observed at least 30 per cent of the samples across different grades. Surprisingly, it was frequently observed in clinically insignificant Gleason score 6 tumors, indicating that chromothripsis does not define more aggressive phenotype. The degree of chromothripsis did not increase significantly in tumors of advanced grades and did not appear to contribute to tumor progression. Our data showed that distribution of chromothriptic rearrangements differed from that of fragile sites but correlated with the size of chromosomes. We also provided evidence that rearrangements resulting from chromothripsis were present in the cells of neighboring Gleason patterns of the same tumor. Our data suggest that that chromothripsis plays role in prostate cancer initiation. GRCh37/hg19 Yes NA CTDB0432 Research 26168399 George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, Leenders F, Lu X, Fernandez-Cuesta L, Bosco G, Muller C, Dahmen I, Jahchan NS, Park KS, Yang D, Karnezis AN, Vaka D, Torres A, Wang MS, Korbel JO, Menon R, Chun SM, Kim D, Wilkerson M, Hayes N, Engelmann D, Putzer B, Bos M, Michels S, Vlasic I, Seidel D, Pinther B, Schaub P, Becker C, Altmuller J, Yokota J, Kohno T, Iwakawa R, Tsuta K, Noguchi M, Muley T, Hoffmann H, Schnabel PA, Petersen I, Chen Y, Soltermann A, Tischler V, Choi CM, Kim YH, Massion PP, Zou Y, Jovanovic D, Kontic M, Wright GM, Russell PA, Solomon B, Koch I, Lindner M, Muscarella LA, la Torre A, Field JK, Jakopovic M, Knezevic J, Castanos-Velez E, Roz L, Pastorino U, Brustugun OT, Lund-Iversen M, Thunnissen E, Kohler J, Schuler M, Botling J, Sandelin M, Sanchez-Cespedes M, Salvesen HB, Achter V, Lang U, Bogus M, Schneider PM, Zander T, Ansen S, Hallek M, Wolf J, Vingron M, Yatabe Y, Travis WD, Nurnberg P, Reinhardt C, Perner S, Heukamp L, Buttner R, Haas SA, Brambilla E, Peifer M, Sage J, Thomas RK Comprehensive genomic profiles of small cell lung cancer Nature 2015 Aug 3,11 Small cell lung cancers Next Generation Sequencing Homo sapiens S02297 Illumina HiSeq 2000 hs1:20723373-20723373,hs11:121660894-121660894;hs1:20738817-20738817,hs1:26956531-26956531;hs1:27101463-27101463,hs11:121026214-121026214;hs1:188615933-188615933,hs18:25019920-25019920;hs3:1174556-1174556,hs3:24628811-24628811;hs3:1254115-1254115,hs3:124877003-124877003;hs3:1263663-1263663,hs3:155832004-155832004;hs3:1289250-1289250,hs3:178243878-178243878;hs3:1302810-1302810,hs11:35725103-35725103;hs3:1342076-1342076,hs3:64531030-64531030;hs3:1342553-1342553,hs3:89167031-89167031;hs3:1633950-1633950,hs11:114476322-114476322;hs3:1686204-1686204,hs11:75840211-75840211;hs3:1797296-1797296,hs3:7395839-7395839;hs3:1906582-1906582,hs11:34095624-34095624;hs3:1961173-1961173,hs3:7991553-7991553;hs3:1967957-1967957,hs3:185346908-185346908;hs3:2070431-2070431,hs11:39388938-39388938;hs3:2072521-2072521,hs11:97444115-97444115;hs3:2103287-2103287,hs3:55498995-55498995;hs3:2105311-2105311,hs3:63030396-63030396;hs3:2134951-2134951,hs3:160557563-160557563;hs3:2202783-2202783,hs3:3777590-3777590;hs3:2223685-2223685,hs11:94728013-94728013;hs3:2270947-2270947,hs3:192946446-192946446;hs3:2277074-2277074,hs11:48932216-48932216;hs3:2281289-2281289,hs3:5605318-5605318;hs3:2299611-2299611,hs11:16323254-16323254;hs3:2353943-2353943,hs3:38503194-38503194;hs3:2391721-2391721,hs3:124962949-124962949;hs3:2403100-2403100,hs11:62971420-62971420;hs3:2416857-2416857,hs11:21742046-21742046;hs3:2432670-2432670,hs3:133364168-133364168;hs3:2473536-2473536,hs3:131504467-131504467;hs3:2774240-2774240,hs11:92704906-92704906;hs3:2823849-2823849,hs11:129616464-129616464;hs3:2876434-2876434,hs3:148402466-148402466;hs3:2953576-2953576,hs3:59626472-59626472;hs3:2970413-2970413,hs11:87487406-87487406;hs3:3014343-3014343,hs3:48997436-48997436;hs3:3165645-3165645,hs3:131355079-131355079;hs3:3348933-3348933,hs3:35878299-35878299;hs3:3354236-3354236,hs3:119555915-119555915;hs3:3354584-3354584,hs3:193187542-193187542;hs3:3364921-3364921,hs11:51398785-51398785;hs3:3757402-3757402,hs11:18313688-18313688;hs3:3793167-3793167,hs3:164510523-164510523;hs3:3832386-3832386,hs11:42085961-42085961;hs3:3968328-3968328,hs11:63561177-63561177;hs3:4289239-4289239,hs3:162350021-162350021;hs3:4387673-4387673,hs3:111374669-111374669;hs3:4388465-4388465,hs11:27705537-27705537;hs3:4401003-4401003,hs3:124943124-124943124;hs3:4421095-4421095,hs3:18057730-18057730;hs3:4427031-4427031,hs11:105713067-105713067;hs3:4429505-4429505,hs3:155841325-155841325;hs3:4446606-4446606,hs3:23643044-23643044;hs3:4464579-4464579,hs3:52816448-52816448;hs3:4464923-4464923,hs11:122699920-122699920;hs3:4484718-4484718,hs3:145610828-145610828;hs3:4499742-4499742,hs3:197734108-197734108;hs3:4631569-4631569,hs11:29545791-29545791;hs3:4780002-4780002,hs11:73363590-73363590;hs3:5056686-5056686,hs3:65629641-65629641;hs3:5062118-5062118,hs11:106414655-106414655;hs3:5086481-5086481,hs11:49265869-49265869;hs3:5178838-5178838,hs11:48052864-48052864;hs3:5184250-5184250,hs3:46590368-46590368;hs3:5226576-5226576,hs3:176757382-176757382;hs3:5231358-5231358,hs11:63797010-63797010;hs3:5272058-5272058,hs3:61778797-61778797;hs3:5284124-5284124,hs11:42758262-42758262;hs3:5316290-5316290,hs3:34641617-34641617;hs3:5316290-5316290,hs3:34641617-34641617;hs3:5332679-5332679,hs3:51579692-51579692;hs3:5472743-5472743,hs3:152927722-152927722;hs3:5474838-5474838,hs3:95911935-95911935;hs3:5477705-5477705,hs3:127406262-127406262;hs3:5536687-5536687,hs3:11110582-11110582;hs3:5588722-5588722,hs3:137137796-137137796;hs3:5604156-5604156,hs11:22234630-22234630;hs3:5613215-5613215,hs11:62762864-62762864;hs3:5623235-5623235,hs3:37423348-37423348;hs3:5808999-5808999,hs3:116817440-116817440;hs3:5863050-5863050,hs3:65204306-65204306;hs3:5894443-5894443,hs3:95365551-95365551;hs3:5923970-5923970,hs3:109951257-109951257;hs3:5933928-5933928,hs3:49068489-49068489;hs3:5956126-5956126,hs11:96209185-96209185;hs3:5959657-5959657,hs3:99903676-99903676;hs3:6032546-6032546,hs11:123780812-123780812;hs3:6278094-6278094,hs11:40356594-40356594;hs3:6514422-6514422,hs3:85513337-85513337;hs3:6570367-6570367,hs3:187994582-187994582;hs3:7014607-7014607,hs11:86900358-86900358;hs3:7172850-7172850,hs3:179094844-179094844;hs3:7174786-7174786,hs3:58340914-58340914;hs3:7217275-7217275,hs11:38918624-38918624;hs3:7217799-7217799,hs3:65255637-65255637;hs3:7401353-7401353,hs11:101608878-101608878;hs3:7450475-7450475,hs3:121188779-121188779;hs3:7922341-7922341,hs11:111567107-111567107;hs3:7951926-7951926,hs3:51034102-51034102;hs3:7971276-7971276,hs3:134159155-134159155;hs3:8011601-8011601,hs3:43217255-43217255;hs3:8025849-8025849,hs11:46036655-46036655;hs3:8145920-8145920,hs3:53102476-53102476;hs3:8211029-8211029,hs3:112526886-112526886;hs3:9188341-9188341,hs3:89456681-89456681;hs3:9203666-9203666,hs11:16049899-16049899;hs3:9389709-9389709,hs3:172998898-172998898;hs3:9399648-9399648,hs3:101229309-101229309;hs3:9401903-9401903,hs11:117385104-117385104;hs3:9421510-9421510,hs3:98155884-98155884;hs3:9428412-9428412,hs11:45939455-45939455;hs3:9471933-9471933,hs3:120834139-120834139;hs3:9587649-9587649,hs3:48532958-48532958;hs3:9797782-9797782,hs11:16960337-16960337;hs3:9803284-9803284,hs11:106447925-106447925;hs3:9863426-9863426,hs11:71839371-71839371;hs3:9864431-9864431,hs11:94042020-94042020;hs3:9929048-9929048,hs3:110391887-110391887;hs3:10072137-10072137,hs3:12548057-12548057;hs3:10085639-10085639,hs3:49436928-49436928;hs3:10319182-10319182,hs3:33822882-33822882;hs3:10352810-10352810,hs11:33465517-33465517;hs3:10366240-10366240,hs11:4876038-4876038;hs3:10412444-10412444,hs11:123502327-123502327;hs3:10418211-10418211,hs11:81286979-81286979;hs3:10551730-10551730,hs11:59684348-59684348;hs3:10667079-10667079,hs11:1496837-1496837;hs3:10686933-10686933,hs3:158576693-158576693;hs3:10844461-10844461,hs11:107079696-107079696;hs3:10921625-10921625,hs11:19980458-19980458;hs3:10945104-10945104,hs11:117328095-117328095;hs3:11245844-11245844,hs11:119397939-119397939;hs3:11252990-11252990,hs3:58636307-58636307;hs3:11254357-11254357,hs11:15524963-15524963;hs3:11269694-11269694,hs3:133481074-133481074;hs3:11279030-11279030,hs11:61210318-61210318;hs3:11323799-11323799,hs11:81813514-81813514;hs3:11419415-11419415,hs3:43719587-43719587;hs3:11523859-11523859,hs3:133309302-133309302;hs3:11548966-11548966,hs11:29386662-29386662;hs3:11549314-11549314,hs3:69490798-69490798;hs3:11549314-11549314,hs3:69490798-69490798;hs3:11752290-11752290,hs11:94626715-94626715;hs3:11762778-11762778,hs3:105082055-105082055;hs3:11778094-11778094,hs11:72408791-72408791;hs3:11779452-11779452,hs11:3846032-3846032;hs3:11911460-11911460,hs3:26384235-26384235;hs3:12196405-12196405,hs11:9004370-9004370;hs3:12213490-12213490,hs11:94046257-94046257;hs3:12349666-12349666,hs3:120755727-120755727;hs3:12388811-12388811,hs11:92495897-92495897;hs3:12564574-12564574,hs3:174986299-174986299;hs3:12565180-12565180,hs11:40920389-40920389;hs3:12836517-12836517,hs3:48482460-48482460;hs3:12868335-12868335,hs3:130665185-130665185;hs3:12930114-12930114,hs11:18009028-18009028;hs3:12947027-12947027,hs11:119552131-119552131;hs3:12950416-12950416,hs11:105460939-105460939;hs3:12971102-12971102,hs11:69206357-69206357;hs3:13147981-13147981,hs3:130973759-130973759;hs3:13200044-13200044,hs3:131321541-131321541;hs3:13277731-13277731,hs3:13278500-13278500;hs3:13277751-13277751,hs3:111294036-111294036;hs3:13279265-13279265,hs3:122022770-122022770;hs3:13389400-13389400,hs11:33766008-33766008;hs3:13415504-13415504,hs11:85033996-85033996;hs3:13440287-13440287,hs3:126825157-126825157;hs3:13519615-13519615,hs11:31746269-31746269;hs3:13604855-13604855,hs11:57043465-57043465;hs3:13629620-13629620,hs11:68139940-68139940;hs3:13661452-13661452,hs11:65446054-65446054;hs3:13667534-13667534,hs3:148372934-148372934;hs3:13789846-13789846,hs3:58634598-58634598;hs3:13791862-13791862,hs11:67795316-67795316;hs3:13795819-13795819,hs11:51592604-51592604;hs3:13801843-13801843,hs11:96096740-96096740;hs3:13889430-13889430,hs11:93559659-93559659;hs3:13984945-13984945,hs3:51513050-51513050;hs3:14100459-14100459,hs3:97667470-97667470;hs3:14259108-14259108,hs11:128790366-128790366;hs3:14269240-14269240,hs11:123369408-123369408;hs3:14275521-14275521,hs11:1113509-1113509;hs3:14282268-14282268,hs11:48068679-48068679;hs3:14292905-14292905,hs3:52256272-52256272;hs3:14684390-14684390,hs3:112721282-112721282;hs3:14684914-14684914,hs3:121264413-121264413;hs3:14684914-14684914,hs3:121264414-121264414;hs3:14749131-14749131,hs3:197704161-197704161;hs3:14758471-14758471,hs3:71874241-71874241;hs3:14769380-14769380,hs11:41607058-41607058;hs3:15019607-15019607,hs3:130491648-130491648;hs3:15097646-15097646,hs3:83433616-83433616;hs3:15454205-15454205,hs3:112919345-112919345;hs3:15503490-15503490,hs3:48456287-48456287;hs3:15535145-15535145,hs3:94267477-94267477;hs3:15569105-15569105,hs3:125121350-125121350;hs3:15577844-15577844,hs3:77275627-77275627;hs3:15605246-15605246,hs3:197729115-197729115;hs3:15685609-15685609,hs3:171372645-171372645;hs3:15686163-15686163,hs3:176932619-176932619;hs3:15731143-15731143,hs3:132793116-132793116;hs3:15745071-15745071,hs11:56880155-56880155;hs3:15750093-15750093,hs11:21139275-21139275;hs3:15854739-15854739,hs11:89959504-89959504;hs3:15903541-15903541,hs3:106190469-106190469;hs3:15996693-15996693,hs11:44966773-44966773;hs3:15999640-15999640,hs3:40126922-40126922;hs3:16073806-16073806,hs3:152622691-152622691;hs3:16090238-16090238,hs3:55568480-55568480;hs3:16245145-16245145,hs3:182883838-182883838;hs3:16248100-16248100,hs3:84376054-84376054;hs3:16412503-16412503,hs3:33479723-33479723;hs3:16442552-16442552,hs3:170524092-170524092;hs3:16532219-16532219,hs11:26353334-26353334;hs3:16541979-16541979,hs11:33876406-33876406;hs3:16585967-16585967,hs3:69240691-69240691;hs3:16732825-16732825,hs3:154696180-154696180;hs3:16738729-16738729,hs3:82571598-82571598;hs3:16742669-16742669,hs11:89977758-89977758;hs3:16838683-16838683,hs3:154114085-154114085;hs3:16850936-16850936,hs3:52824704-52824704;hs3:16851506-16851506,hs3:183117444-183117444;hs3:16910463-16910463,hs11:76024438-76024438;hs3:16936601-16936601,hs3:60133534-60133534;hs3:17025909-17025909,hs3:125528440-125528440;hs3:17045170-17045170,hs3:169781688-169781688;hs3:17500113-17500113,hs3:184544334-184544334;hs3:17549781-17549781,hs3:155042059-155042059;hs3:17559202-17559202,hs11:11823433-11823433;hs3:17583553-17583553,hs3:165175820-165175820;hs3:17630370-17630370,hs11:84256143-84256143;hs3:17635154-17635154,hs3:183248537-183248537;hs3:17732210-17732210,hs3:181115355-181115355;hs3:17875933-17875933,hs3:134849942-134849942;hs3:18029769-18029769,hs3:30486410-30486410;hs3:18055514-18055514,hs3:107226421-107226421;hs3:18126575-18126575,hs3:160290487-160290487;hs3:18399398-18399398,hs3:99150519-99150519;hs3:18519737-18519737,hs11:22325602-22325602;hs3:18778768-18778768,hs3:197523785-197523785;hs3:18782821-18782821,hs3:194517647-194517647;hs3:18895324-18895324,hs3:31085368-31085368;hs3:18916659-18916659,hs3:100284416-100284416;hs3:18950471-18950471,hs11:114725615-114725615;hs3:18950930-18950930,hs3:138068158-138068158;hs3:18958484-18958484,hs3:189750335-189750335;hs3:19093570-19093570,hs11:119396025-119396025;hs3:19166954-19166954,hs11:17122921-17122921;hs3:19220397-19220397,hs11:66142370-66142370;hs3:19230789-19230789,hs11:101934961-101934961;hs3:19232233-19232233,hs11:90084656-90084656;hs3:19266820-19266820,hs11:11745947-11745947;hs3:19311854-19311854,hs11:10791529-10791529;hs3:19339059-19339059,hs11:10197124-10197124;hs3:19360219-19360219,hs3:60192359-60192359;hs3:19362681-19362681,hs11:85833502-85833502;hs3:19420855-19420855,hs3:186234790-186234790;hs3:19474016-19474016,hs11:104468880-104468880;hs3:19497837-19497837,hs3:143396804-143396804;hs3:19520730-19520730,hs3:123474193-123474193;hs3:19530690-19530690,hs3:67927770-67927770;hs3:19555846-19555846,hs3:149635801-149635801;hs3:19558016-19558016,hs11:73433990-73433990;hs3:19975086-19975086,hs3:36124179-36124179;hs3:20127529-20127529,hs3:146360426-146360426;hs3:20128383-20128383,hs11:69688700-69688700;hs3:20171954-20171954,hs3:62754628-62754628;hs3:20731213-20731213,hs3:56681927-56681927;hs3:20854277-20854277,hs3:77115111-77115111;hs3:20866782-20866782,hs11:47997242-47997242;hs3:20899844-20899844,hs3:100313205-100313205;hs3:20902547-20902547,hs3:31100140-31100140;hs3:20929413-20929413,hs3:154768109-154768109;hs3:21142948-21142948,hs11:65695354-65695354;hs3:21154436-21154436,hs11:100062787-100062787;hs3:21161412-21161412,hs11:94623792-94623792;hs3:21271341-21271341,hs11:55444802-55444802;hs3:21890997-21890997,hs3:78137795-78137795;hs3:22005835-22005835,hs3:80575674-80575674;hs3:22177014-22177014,hs3:190062071-190062071;hs3:22481153-22481153,hs11:131303398-131303398;hs3:22625405-22625405,hs3:107625722-107625722;hs3:22688482-22688482,hs3:65840210-65840210;hs3:22878536-22878536,hs11:84647582-84647582;hs3:22899786-22899786,hs11:99518075-99518075;hs3:22931688-22931688,hs11:81810963-81810963;hs3:22989496-22989496,hs3:36841529-36841529;hs3:22992825-22992825,hs11:101212434-101212434;hs3:23035109-23035109,hs11:18507769-18507769;hs3:23044297-23044297,hs3:80603896-80603896;hs3:23050536-23050536,hs3:54410278-54410278;hs3:23136537-23136537,hs3:39629764-39629764;hs3:23140105-23140105,hs11:34599561-34599561;hs3:23181764-23181764,hs3:46779753-46779753;hs3:23332100-23332100,hs3:193819556-193819556;hs3:23369813-23369813,hs3:121054620-121054620;hs3:23380064-23380064,hs3:170626102-170626102;hs3:23466190-23466190,hs3:109609360-109609360;hs3:23467168-23467168,hs3:104349912-104349912;hs3:23521925-23521925,hs3:158469391-158469391;hs3:23523848-23523848,hs3:45268493-45268493;hs3:23639130-23639130,hs3:95937027-95937027;hs3:23757936-23757936,hs11:100543056-100543056;hs3:23760348-23760348,hs3:172905451-172905451;hs3:23842907-23842907,hs11:55354825-55354825;hs3:23892423-23892423,hs11:86931141-86931141;hs3:23913471-23913471,hs3:66720238-66720238;hs3:23920201-23920201,hs11:109695441-109695441;hs3:23924792-23924792,hs3:29191942-29191942;hs3:24061570-24061570,hs11:575781-575781;hs3:24200751-24200751,hs3:173543356-173543356;hs3:24257224-24257224,hs11:65097932-65097932;hs3:24300228-24300228,hs11:46946408-46946408;hs3:24393092-24393092,hs11:74968010-74968010;hs3:24459212-24459212,hs11:109956524-109956524;hs3:24476639-24476639,hs11:69440969-69440969;hs3:24491505-24491505,hs11:83309689-83309689;hs3:24500581-24500581,hs3:170846800-170846800;hs3:24508586-24508586,hs3:176989714-176989714;hs3:24515408-24515408,hs11:76656737-76656737;hs3:24563283-24563283,hs3:70202315-70202315;hs3:24602594-24602594,hs11:210916-210916;hs3:24640410-24640410,hs3:69770783-69770783;hs3:24715356-24715356,hs11:42290285-42290285;hs3:24763288-24763288,hs3:118665416-118665416;hs3:24914208-24914208,hs11:58626926-58626926;hs3:24918013-24918013,hs3:40396448-40396448;hs3:24936973-24936973,hs3:108612303-108612303;hs3:25116945-25116945,hs11:85489359-85489359;hs3:25167536-25167536,hs3:127437091-127437091;hs3:25179792-25179792,hs11:43991733-43991733;hs3:25221380-25221380,hs3:194451033-194451033;hs3:25223107-25223107,hs3:128417144-128417144;hs3:25238973-25238973,hs3:121936764-121936764;hs3:25502535-25502535,hs3:74013942-74013942;hs3:25614517-25614517,hs11:57918253-57918253;hs3:25651483-25651483,hs3:144410689-144410689;hs3:25652673-25652673,hs11:25714372-25714372;hs3:26163702-26163702,hs11:12350384-12350384;hs3:26209863-26209863,hs3:128909135-128909135;hs3:26224079-26224079,hs11:102503326-102503326;hs3:26239910-26239910,hs11:36061215-36061215;hs3:26242365-26242365,hs11:13240329-13240329;hs3:26248278-26248278,hs11:75155632-75155632;hs3:26264249-26264249,hs3:182101667-182101667;hs3:26312995-26312995,hs3:123881001-123881001;hs3:26315238-26315238,hs11:105350015-105350015;hs3:26343265-26343265,hs3:182122706-182122706;hs3:26343941-26343941,hs11:130711930-130711930;hs3:26490395-26490395,hs11:61114338-61114338;hs3:26578700-26578700,hs11:104826516-104826516;hs3:26710229-26710229,hs3:122326460-122326460;hs3:26764845-26764845,hs11:98635183-98635183;hs3:26894693-26894693,hs3:109353616-109353616;hs3:26930532-26930532,hs11:48837008-48837008;hs3:26982471-26982471,hs11:85985548-85985548;hs3:27029818-27029818,hs3:109599140-109599140;hs3:27043917-27043917,hs3:164727730-164727730;hs3:27143746-27143746,hs3:87005961-87005961;hs3:27365419-27365419,hs3:190022491-190022491;hs3:27381829-27381829,hs11:15040010-15040010;hs3:27487908-27487908,hs3:131546881-131546881;hs3:27522788-27522788,hs3:142579374-142579374;hs3:27554814-27554814,hs11:97732632-97732632;hs3:27655618-27655618,hs3:55762169-55762169;hs3:27658313-27658313,hs3:76669921-76669921;hs3:27674518-27674518,hs11:107038598-107038598;hs3:27740580-27740580,hs3:169774231-169774231;hs3:27935915-27935915,hs3:109486732-109486732;hs3:28049530-28049530,hs3:69113905-69113905;hs3:28151945-28151945,hs3:79730088-79730088;hs3:28220280-28220280,hs11:44936805-44936805;hs3:28278940-28278940,hs3:155461057-155461057;hs3:28300769-28300769,hs3:60060021-60060021;hs3:28424923-28424923,hs3:183473223-183473223;hs3:28582146-28582146,hs11:93577831-93577831;hs3:28603122-28603122,hs3:165657172-165657172;hs3:28607261-28607261,hs11:46018022-46018022;hs3:28615434-28615434,hs3:45637189-45637189;hs3:28635572-28635572,hs3:71750622-71750622;hs3:28637130-28637130,hs3:180725378-180725378;hs3:29044651-29044651,hs11:40516309-40516309;hs3:29142845-29142845,hs11:94251859-94251859;hs3:29166198-29166198,hs3:140523265-140523265;hs3:29167636-29167636,hs11:34202976-34202976;hs3:29201099-29201099,hs3:172922818-172922818;hs3:29287976-29287976,hs3:191053254-191053254;hs3:29313650-29313650,hs3:100281304-100281304;hs3:29320504-29320504,hs3:120171163-120171163;hs3:29321110-29321110,hs3:192185858-192185858;hs3:29336878-29336878,hs11:80795946-80795946;hs3:29392284-29392284,hs3:126696948-126696948;hs3:29715162-29715162,hs3:71398031-71398031;hs3:29931407-29931407,hs3:191249779-191249779;hs3:29987934-29987934,hs3:30605069-30605069;hs3:30035330-30035330,hs11:32050780-32050780;hs3:30042092-30042092,hs3:98859739-98859739;hs3:30291608-30291608,hs11:72932029-72932029;hs3:30295465-30295465,hs3:148494373-148494373;hs3:30382079-30382079,hs11:27671626-27671626;hs3:30389159-30389159,hs11:113544185-113544185;hs3:30510107-30510107,hs11:62772452-62772452;hs3:30614167-30614167,hs3:109946523-109946523;hs3:30685481-30685481,hs3:117301596-117301596;hs3:30687210-30687210,hs11:98694242-98694242;hs3:30697981-30697981,hs11:67771441-67771441;hs3:30710906-30710906,hs11:1002418-1002418;hs3:30716362-30716362,hs3:195592255-195592255;hs3:30748972-30748972,hs3:141156353-141156353;hs3:30812189-30812189,hs11:104220747-104220747;hs3:30816916-30816916,hs11:46756780-46756780;hs3:30831323-30831323,hs3:187560516-187560516;hs3:30979849-30979849,hs11:21945228-21945228;hs3:31041403-31041403,hs3:103091379-103091379;hs3:31041403-31041403,hs3:103091378-103091378;hs3:31243966-31243966,hs3:82846908-82846908;hs3:31245679-31245679,hs3:62686923-62686923;hs3:31274589-31274589,hs11:81292773-81292773;hs3:31334830-31334830,hs11:24215638-24215638;hs3:31344833-31344833,hs11:76262366-76262366;hs3:31436366-31436366,hs11:30838641-30838641;hs3:31556786-31556786,hs3:89778431-89778431;hs3:31566025-31566025,hs11:3014952-3014952;hs3:31575409-31575409,hs11:65367411-65367411;hs3:31628485-31628485,hs11:86101362-86101362;hs3:31638947-31638947,hs3:40227971-40227971;hs3:31712566-31712566,hs11:10828466-10828466;hs3:31901423-31901423,hs3:41631050-41631050;hs3:32072394-32072394,hs3:181500689-181500689;hs3:32100503-32100503,hs3:193136837-193136837;hs3:32279436-32279436,hs11:50213009-50213009;hs3:32375696-32375696,hs3:192059105-192059105;hs3:32410597-32410597,hs3:36826800-36826800;hs3:32425160-32425160,hs3:128909899-128909899;hs3:32425160-32425160,hs3:128909900-128909900;hs3:32572940-32572940,hs3:86317885-86317885;hs3:32577425-32577425,hs3:146781680-146781680;hs3:33319427-33319427,hs11:34003302-34003302;hs3:33327155-33327155,hs11:103745828-103745828;hs3:33346990-33346990,hs11:17709218-17709218;hs3:33402818-33402818,hs3:183572609-183572609;hs3:33407072-33407072,hs11:59453907-59453907;hs3:33425119-33425119,hs3:188345187-188345187;hs3:33706795-33706795,hs3:146582044-146582044;hs3:33730137-33730137,hs3:191259534-191259534;hs3:33746256-33746256,hs3:159772330-159772330;hs3:33751728-33751728,hs11:99889665-99889665;hs3:33806555-33806555,hs3:110338036-110338036;hs3:33819862-33819862,hs11:109542024-109542024;hs3:33828491-33828491,hs3:191883241-191883241;hs3:33834686-33834686,hs11:94475719-94475719;hs3:33841378-33841378,hs11:32589126-32589126;hs3:33859878-33859878,hs11:91031567-91031567;hs3:34406461-34406461,hs3:63114443-63114443;hs3:34423257-34423257,hs3:99712755-99712755;hs3:34427587-34427587,hs3:119386022-119386022;hs3:34543625-34543625,hs3:134168237-134168237;hs3:34544224-34544224,hs11:122698908-122698908;hs3:34592210-34592210,hs3:167114787-167114787;hs3:35014603-35014603,hs3:189136834-189136834;hs3:35020078-35020078,hs11:68135809-68135809;hs3:35130310-35130310,hs11:130529323-130529323;hs3:35195569-35195569,hs3:104571952-104571952;hs3:35273000-35273000,hs3:50342050-50342050;hs3:35318544-35318544,hs3:154818979-154818979;hs3:35331098-35331098,hs11:66290097-66290097;hs3:35338813-35338813,hs11:65845934-65845934;hs3:35881329-35881329,hs3:96799761-96799761;hs3:36096089-36096089,hs11:18566818-18566818;hs3:36116611-36116611,hs3:77325527-77325527;hs3:36162058-36162058,hs3:96973221-96973221;hs3:36173620-36173620,hs11:36217551-36217551;hs3:36179677-36179677,hs11:67471378-67471378;hs3:36204130-36204130,hs3:162239240-162239240;hs3:36250785-36250785,hs3:165667457-165667457;hs3:36435618-36435618,hs3:144304003-144304003;hs3:36519181-36519181,hs3:132761806-132761806;hs3:36536064-36536064,hs3:110343394-110343394;hs3:36583485-36583485,hs3:58089500-58089500;hs3:36650254-36650254,hs3:123430565-123430565;hs3:36739841-36739841,hs11:1510997-1510997;hs3:36741099-36741099,hs3:150229379-150229379;hs3:36793635-36793635,hs11:15513772-15513772;hs3:36846135-36846135,hs3:164950480-164950480;hs3:36945903-36945903,hs3:69388175-69388175;hs3:36969002-36969002,hs11:120588342-120588342;hs3:36970214-36970214,hs11:86496767-86496767;hs3:36984550-36984550,hs3:89430797-89430797;hs3:36984830-36984830,hs3:131324507-131324507;hs3:36984829-36984829,hs3:131324508-131324508;hs3:37093613-37093613,hs11:13144094-13144094;hs3:37178710-37178710,hs11:2546855-2546855;hs3:37282759-37282759,hs11:23586039-23586039;hs3:37307526-37307526,hs3:66709715-66709715;hs3:37350253-37350253,hs3:53551204-53551204;hs3:37350927-37350927,hs3:42184206-42184206;hs3:37393912-37393912,hs11:27534368-27534368;hs3:37418000-37418000,hs11:127594502-127594502;hs3:37422370-37422370,hs3:115892347-115892347;hs3:37573074-37573074,hs3:175731962-175731962;hs3:37581731-37581731,hs3:59296490-59296490;hs3:37582372-37582372,hs11:27280627-27280627;hs3:37584794-37584794,hs11:129667225-129667225;hs3:37616284-37616284,hs3:97172119-97172119;hs3:37671747-37671747,hs11:103597120-103597120;hs3:37881815-37881815,hs3:47821127-47821127;hs3:38040318-38040318,hs3:137023405-137023405;hs3:38069622-38069622,hs11:67205966-67205966;hs3:38232821-38232821,hs11:28876095-28876095;hs3:38251947-38251947,hs11:55731918-55731918;hs3:38278879-38278879,hs11:59336797-59336797;hs3:38285025-38285025,hs11:49274921-49274921;hs3:38287642-38287642,hs11:73415992-73415992;hs3:38325831-38325831,hs11:21374988-21374988;hs3:38595485-38595485,hs3:195614637-195614637;hs3:38694694-38694694,hs3:158422135-158422135;hs3:38694915-38694915,hs3:122103051-122103051;hs3:38701252-38701252,hs3:64713664-64713664;hs3:38782059-38782059,hs11:78173116-78173116;hs3:38782237-38782237,hs3:176623761-176623761;hs3:38826318-38826318,hs3:165038534-165038534;hs3:38870661-38870661,hs11:22225618-22225618;hs3:38894622-38894622,hs11:45207442-45207442;hs3:38932854-38932854,hs11:62217993-62217993;hs3:38990619-38990619,hs3:101257702-101257702;hs3:39246141-39246141,hs11:98647121-98647121;hs3:39309699-39309699,hs3:118900329-118900329;hs3:39572730-39572730,hs3:130193136-130193136;hs3:39659385-39659385,hs11:60808638-60808638;hs3:39666453-39666453,hs11:42421135-42421135;hs3:39704734-39704734,hs3:189555263-189555263;hs3:39716110-39716110,hs3:167010415-167010415;hs3:39863734-39863734,hs3:61710562-61710562;hs3:39864543-39864543,hs11:58019473-58019473;hs3:39963335-39963335,hs3:137901156-137901156;hs3:39994807-39994807,hs11:130084711-130084711;hs3:40056578-40056578,hs11:79385100-79385100;hs3:40074752-40074752,hs3:97187323-97187323;hs3:40112976-40112976,hs3:101946231-101946231;hs3:40116074-40116074,hs3:178216395-178216395;hs3:40407861-40407861,hs3:123933218-123933218;hs3:40509735-40509735,hs11:129167097-129167097;hs3:40787309-40787309,hs11:62315744-62315744;hs3:40790043-40790043,hs3:169409118-169409118;hs3:41160455-41160455,hs3:181931741-181931741;hs3:41185097-41185097,hs11:12600668-12600668;hs3:41194004-41194004,hs3:116324158-116324158;hs3:41196393-41196393,hs11:110864994-110864994;hs3:41241327-41241327,hs3:47842088-47842088;hs3:41250779-41250779,hs3:189250807-189250807;hs3:41352735-41352735,hs3:70855483-70855483;hs3:41546863-41546863,hs11:104698151-104698151;hs3:41688025-41688025,hs11:105377270-105377270;hs3:41737300-41737300,hs11:97442342-97442342;hs3:41947954-41947954,hs11:223075-223075;hs3:42003168-42003168,hs3:73007391-73007391;hs3:42007266-42007266,hs11:83350759-83350759;hs3:42021582-42021582,hs11:67588675-67588675;hs3:42052640-42052640,hs11:45216681-45216681;hs3:42058131-42058131,hs3:128624762-128624762;hs3:42113827-42113827,hs11:1025523-1025523;hs3:42183582-42183582,hs11:18429111-18429111;hs3:42242256-42242256,hs3:117329417-117329417;hs3:42259321-42259321,hs11:92170510-92170510;hs3:42665015-42665015,hs11:96969447-96969447;hs3:42689634-42689634,hs11:128997999-128997999;hs3:42707912-42707912,hs3:105113997-105113997;hs3:42735017-42735017,hs11:19489568-19489568;hs3:42773674-42773674,hs3:73036819-73036819;hs3:42940983-42940983,hs3:49114922-49114922;hs3:42942277-42942277,hs3:133326998-133326998;hs3:43021227-43021227,hs3:119818778-119818778;hs3:43053685-43053685,hs11:64490207-64490207;hs3:43054431-43054431,hs3:168750465-168750465;hs3:43054431-43054431,hs3:168750464-168750464;hs3:43217534-43217534,hs11:30173871-30173871;hs3:43253363-43253363,hs11:77884219-77884219;hs3:43315455-43315455,hs11:75362166-75362166;hs3:43317603-43317603,hs11:48923331-48923331;hs3:43443534-43443534,hs3:139356539-139356539;hs3:43463667-43463667,hs3:178927608-178927608;hs3:43467028-43467028,hs3:161947797-161947797;hs3:43533490-43533490,hs3:130917265-130917265;hs3:43552086-43552086,hs11:23936982-23936982;hs3:43661447-43661447,hs3:76642146-76642146;hs3:43720819-43720819,hs3:95290894-95290894;hs3:43726118-43726118,hs11:43707765-43707765;hs3:44141642-44141642,hs11:24655829-24655829;hs3:44144867-44144867,hs3:185831220-185831220;hs3:44234731-44234731,hs11:16345776-16345776;hs3:44247170-44247170,hs3:75533310-75533310;hs3:44248060-44248060,hs11:103695725-103695725;hs3:44248061-44248061,hs11:103695724-103695724;hs3:44492548-44492548,hs3:118118803-118118803;hs3:44507737-44507737,hs11:50220334-50220334;hs3:44509683-44509683,hs3:147839147-147839147;hs3:44510168-44510168,hs3:89550106-89550106;hs3:44817190-44817190,hs11:44351060-44351060;hs3:44835456-44835456,hs3:54847284-54847284;hs3:44899199-44899199,hs3:69424224-69424224;hs3:45035853-45035853,hs3:62481604-62481604;hs3:45042360-45042360,hs3:189146522-189146522;hs3:45101063-45101063,hs3:63829305-63829305;hs3:45149728-45149728,hs3:116348145-116348145;hs3:45182269-45182269,hs3:182366783-182366783;hs3:45266432-45266432,hs11:85243746-85243746;hs3:45323690-45323690,hs3:62318811-62318811;hs3:45374487-45374487,hs11:67412469-67412469;hs3:45393052-45393052,hs11:129719702-129719702;hs3:45553767-45553767,hs11:4746692-4746692;hs3:45557162-45557162,hs3:188386906-188386906;hs3:45578786-45578786,hs3:87282502-87282502;hs3:45589829-45589829,hs3:99273738-99273738;hs3:45729230-45729230,hs11:43980261-43980261;hs3:45732479-45732479,hs3:62155535-62155535;hs3:45781476-45781476,hs11:83938172-83938172;hs3:45788108-45788108,hs11:65353981-65353981;hs3:45902617-45902617,hs3:140067576-140067576;hs3:45909489-45909489,hs3:79895842-79895842;hs3:45987615-45987615,hs3:124956909-124956909;hs3:46014154-46014154,hs11:57452691-57452691;hs3:46096435-46096435,hs3:127090976-127090976;hs3:46098551-46098551,hs11:64205525-64205525;hs3:46162605-46162605,hs3:182219407-182219407;hs3:46182573-46182573,hs3:124369549-124369549;hs3:46204731-46204731,hs11:114205300-114205300;hs3:46209209-46209209,hs11:90772955-90772955;hs3:46303237-46303237,hs11:106885098-106885098;hs3:46317156-46317156,hs11:127240605-127240605;hs3:46350173-46350173,hs3:187206278-187206278;hs3:46417183-46417183,hs3:168285448-168285448;hs3:46436188-46436188,hs3:65045469-65045469;hs3:46438370-46438370,hs3:85357252-85357252;hs3:46561074-46561074,hs3:189711842-189711842;hs3:46594170-46594170,hs3:197529844-197529844;hs3:46753271-46753271,hs11:62374186-62374186;hs3:46784649-46784649,hs3:133400349-133400349;hs3:46872799-46872799,hs3:121788305-121788305;hs3:47037075-47037075,hs3:109645645-109645645;hs3:47068347-47068347,hs11:62277811-62277811;hs3:47124273-47124273,hs3:179355585-179355585;hs3:47128833-47128833,hs3:170086445-170086445;hs3:47135139-47135139,hs11:12650234-12650234;hs3:47140448-47140448,hs3:182623300-182623300;hs3:47173426-47173426,hs11:18396121-18396121;hs3:47177299-47177299,hs3:128923881-128923881;hs3:47221853-47221853,hs11:41628868-41628868;hs3:47223779-47223779,hs3:196975381-196975381;hs3:47233768-47233768,hs11:27427105-27427105;hs3:47237389-47237389,hs11:62472844-62472844;hs3:47280356-47280356,hs11:8985751-8985751;hs3:47284024-47284024,hs3:65986687-65986687;hs3:47326456-47326456,hs11:60493736-60493736;hs3:47329329-47329329,hs3:130935005-130935005;hs3:47363372-47363372,hs3:150765583-150765583;hs3:47818878-47818878,hs11:60807537-60807537;hs3:47819356-47819356,hs3:141741564-141741564;hs3:47840631-47840631,hs11:21958275-21958275;hs3:47845406-47845406,hs11:35575920-35575920;hs3:47869739-47869739,hs11:44615743-44615743;hs3:47991278-47991278,hs11:127704815-127704815;hs3:48039463-48039463,hs3:192573169-192573169;hs3:48082476-48082476,hs11:64139170-64139170;hs3:48123129-48123129,hs11:59330288-59330288;hs3:48273395-48273395,hs11:129611127-129611127;hs3:48306417-48306417,hs3:115931595-115931595;hs3:48309576-48309576,hs3:57858958-57858958;hs3:48399717-48399717,hs3:146221990-146221990;hs3:48407924-48407924,hs3:55934385-55934385;hs3:48409410-48409410,hs3:48463642-48463642;hs3:48449751-48449751,hs3:123803169-123803169;hs3:48620207-48620207,hs11:46952126-46952126;hs3:48620207-48620207,hs11:46952127-46952127;hs3:48625045-48625045,hs11:76531188-76531188;hs3:48655838-48655838,hs11:117204971-117204971;hs3:48659097-48659097,hs11:2931121-2931121;hs3:48677400-48677400,hs11:68232171-68232171;hs3:48687150-48687150,hs3:100104697-100104697;hs3:48813619-48813619,hs11:129631075-129631075;hs3:48831150-48831150,hs11:86970577-86970577;hs3:48837712-48837712,hs3:138070913-138070913;hs3:48840209-48840209,hs3:108181009-108181009;hs3:48847664-48847664,hs3:175018777-175018777;hs3:48912501-48912501,hs3:49906104-49906104;hs3:48936308-48936308,hs11:117081342-117081342;hs3:48960988-48960988,hs3:121466157-121466157;hs3:48963192-48963192,hs11:44347097-44347097;hs3:48969562-48969562,hs11:65853390-65853390;hs3:48989115-48989115,hs11:12688424-12688424;hs3:48995757-48995757,hs11:69065871-69065871;hs3:49001528-49001528,hs11:123756423-123756423;hs3:49011931-49011931,hs11:12583822-12583822;hs3:49034595-49034595,hs11:93908891-93908891;hs3:49035946-49035946,hs11:34059545-34059545;hs3:49056500-49056500,hs3:134989256-134989256;hs3:49108476-49108476,hs11:82165605-82165605;hs3:49153327-49153327,hs3:64375128-64375128;hs3:49339000-49339000,hs3:173068556-173068556;hs3:49377679-49377679,hs3:85191290-85191290;hs3:49384124-49384124,hs11:17547440-17547440;hs3:49412860-49412860,hs11:70182714-70182714;hs3:49486754-49486754,hs3:195803221-195803221;hs3:49579217-49579217,hs11:14089136-14089136;hs3:49584399-49584399,hs3:113851256-113851256;hs3:49595212-49595212,hs3:149665765-149665765;hs3:49650987-49650987,hs11:70969941-70969941;hs3:49652786-49652786,hs3:106772969-106772969;hs3:49659485-49659485,hs3:113415676-113415676;hs3:49679573-49679573,hs3:57966568-57966568;hs3:49680244-49680244,hs3:106479259-106479259;hs3:49680244-49680244,hs3:106479259-106479259;hs3:49850707-49850707,hs11:124567382-124567382;hs3:49949823-49949823,hs11:128237510-128237510;hs3:50031628-50031628,hs11:79234796-79234796;hs3:50044395-50044395,hs3:192934519-192934519;hs3:50046857-50046857,hs3:89615790-89615790;hs3:50067555-50067555,hs3:179863740-179863740;hs3:50079828-50079828,hs11:106617916-106617916;hs3:50080374-50080374,hs3:148614007-148614007;hs3:50100239-50100239,hs3:169359288-169359288;hs3:50163333-50163333,hs11:68121953-68121953;hs3:50276531-50276531,hs3:161953770-161953770;hs3:50281953-50281953,hs3:152772689-152772689;hs3:50311264-50311264,hs11:9365704-9365704;hs3:50384668-50384668,hs11:65385852-65385852;hs3:50434094-50434094,hs11:76026843-76026843;hs3:50513868-50513868,hs11:31019561-31019561;hs3:50550768-50550768,hs11:67374069-67374069;hs3:50697526-50697526,hs11:57022371-57022371;hs3:50697991-50697991,hs3:134646342-134646342;hs3:50699463-50699463,hs3:67733089-67733089;hs3:50921759-50921759,hs11:16962796-16962796;hs3:50934199-50934199,hs3:167118921-167118921;hs3:50951707-50951707,hs3:141747771-141747771;hs3:50974922-50974922,hs11:106253995-106253995;hs3:50981887-50981887,hs3:141145059-141145059;hs3:50997381-50997381,hs11:25985789-25985789;hs3:51007884-51007884,hs3:171396887-171396887;hs3:51075252-51075252,hs11:96753649-96753649;hs3:51158653-51158653,hs3:86797933-86797933;hs3:51161763-51161763,hs3:107809860-107809860;hs3:51221986-51221986,hs3:140222025-140222025;hs3:51234484-51234484,hs3:184631898-184631898;hs3:51330418-51330418,hs3:134094581-134094581;hs3:51337878-51337878,hs3:190016476-190016476;hs3:51410202-51410202,hs11:127644625-127644625;hs3:51412443-51412443,hs3:122342908-122342908;hs3:51413402-51413402,hs3:194408015-194408015;hs3:51414344-51414344,hs11:94897191-94897191;hs3:51415161-51415161,hs11:30515539-30515539;hs3:51507359-51507359,hs3:137882823-137882823;hs3:51582724-51582724,hs3:54996121-54996121;hs3:51724299-51724299,hs3:126263096-126263096;hs3:51744049-51744049,hs3:179141190-179141190;hs3:51746333-51746333,hs11:104815085-104815085;hs3:51884108-51884108,hs11:44967636-44967636;hs3:52030967-52030967,hs3:120286203-120286203;hs3:52036552-52036552,hs11:62882169-62882169;hs3:52039318-52039318,hs11:62485394-62485394;hs3:52060396-52060396,hs11:116033820-116033820;hs3:52061416-52061416,hs3:142514522-142514522;hs3:52066383-52066383,hs11:60892632-60892632;hs3:52094918-52094918,hs11:66032456-66032456;hs3:52229744-52229744,hs11:67291556-67291556;hs3:52357197-52357197,hs11:100453079-100453079;hs3:52357437-52357437,hs3:166617408-166617408;hs3:52357436-52357436,hs3:166617409-166617409;hs3:52363588-52363588,hs11:483993-483993;hs3:52366855-52366855,hs11:63531050-63531050;hs3:52375191-52375191,hs3:115650092-115650092;hs3:52471818-52471818,hs3:123215952-123215952;hs3:52519278-52519278,hs11:45197812-45197812;hs3:52546287-52546287,hs3:170865872-170865872;hs3:52610957-52610957,hs11:70185266-70185266;hs3:52667139-52667139,hs11:93130976-93130976;hs3:52808154-52808154,hs3:52808973-52808973;hs3:52808836-52808836,hs11:596932-596932;hs3:52819055-52819055,hs11:41606681-41606681;hs3:52820624-52820624,hs3:179386752-179386752;hs3:53068968-53068968,hs11:94505521-94505521;hs3:53291215-53291215,hs11:96734317-96734317;hs3:53341213-53341213,hs3:163677014-163677014;hs3:53346013-53346013,hs11:74058754-74058754;hs3:53377796-53377796,hs11:89730651-89730651;hs3:53532961-53532961,hs11:46220190-46220190;hs3:53541023-53541023,hs11:47269714-47269714;hs3:53574193-53574193,hs3:190980060-190980060;hs3:53579326-53579326,hs11:33438474-33438474;hs3:53583949-53583949,hs3:73803452-73803452;hs3:53658305-53658305,hs11:76158685-76158685;hs3:53661910-53661910,hs11:33125699-33125699;hs3:53662201-53662201,hs11:45388475-45388475;hs3:53662754-53662754,hs3:63097330-63097330;hs3:53670208-53670208,hs3:109354963-109354963;hs3:53673720-53673720,hs11:62339687-62339687;hs3:53684992-53684992,hs11:128936890-128936890;hs3:53809167-53809167,hs3:62639567-62639567;hs3:53858007-53858007,hs3:184056447-184056447;hs3:53970044-53970044,hs3:169407357-169407357;hs3:54121927-54121927,hs3:173731035-173731035;hs3:54312608-54312608,hs3:119089471-119089471;hs3:54369589-54369589,hs3:99803137-99803137;hs3:54371695-54371695,hs11:96049762-96049762;hs3:54405818-54405818,hs11:63462258-63462258;hs3:54410479-54410479,hs11:21718074-21718074;hs3:54410894-54410894,hs11:36242794-36242794;hs3:54609078-54609078,hs11:3801633-3801633;hs3:54624195-54624195,hs3:65804073-65804073;hs3:54627206-54627206,hs11:130186758-130186758;hs3:54659560-54659560,hs3:146039599-146039599;hs3:54688126-54688126,hs11:67353817-67353817;hs3:54694536-54694536,hs11:118924887-118924887;hs3:54706510-54706510,hs3:85675259-85675259;hs3:54716856-54716856,hs3:84446182-84446182;hs3:54750892-54750892,hs11:85247690-85247690;hs3:54763519-54763519,hs11:103078724-103078724;hs3:54766435-54766435,hs3:174009086-174009086;hs3:54985935-54985935,hs11:393834-393834;hs3:55570636-55570636,hs3:179339279-179339279;hs3:55571153-55571153,hs11:29854746-29854746;hs3:55605944-55605944,hs3:107864679-107864679;hs3:55670368-55670368,hs11:48748437-48748437;hs3:55735817-55735817,hs11:87135116-87135116;hs3:55737311-55737311,hs3:96125286-96125286;hs3:55762735-55762735,hs11:24611326-24611326;hs3:55773828-55773828,hs3:187370103-187370103;hs3:55823130-55823130,hs11:43737628-43737628;hs3:55848055-55848055,hs3:123464146-123464146;hs3:55869967-55869967,hs11:20993180-20993180;hs3:55877551-55877551,hs11:26915448-26915448;hs3:55951658-55951658,hs11:110270961-110270961;hs3:56134925-56134925,hs11:67413663-67413663;hs3:56152635-56152635,hs3:69667137-69667137;hs3:56156996-56156996,hs3:62518684-62518684;hs3:56193229-56193229,hs11:39049176-39049176;hs3:56229342-56229342,hs3:109777907-109777907;hs3:56268571-56268571,hs11:36152686-36152686;hs3:56301205-56301205,hs3:119931892-119931892;hs3:56306732-56306732,hs11:123396061-123396061;hs3:56381466-56381466,hs11:35519589-35519589;hs3:56502293-56502293,hs3:60545139-60545139;hs3:56776675-56776675,hs3:177750636-177750636;hs3:56809526-56809526,hs3:177753717-177753717;hs3:56823584-56823584,hs3:71726942-71726942;hs3:56832728-56832728,hs3:183896421-183896421;hs3:56834794-56834794,hs3:192557377-192557377;hs3:56837689-56837689,hs11:34103641-34103641;hs3:56840976-56840976,hs11:119352177-119352177;hs3:56844377-56844377,hs3:133367363-133367363;hs3:56920638-56920638,hs11:18364681-18364681;hs3:56965827-56965827,hs3:146780866-146780866;hs3:56971391-56971391,hs11:45256966-45256966;hs3:57041627-57041627,hs3:163033087-163033087;hs3:57078424-57078424,hs11:98778064-98778064;hs3:57099856-57099856,hs3:108587763-108587763;hs3:57610565-57610565,hs3:105781420-105781420;hs3:57615359-57615359,hs3:126319087-126319087;hs3:57748787-57748787,hs11:28993195-28993195;hs3:57786407-57786407,hs3:122322395-122322395;hs3:57880958-57880958,hs3:131515910-131515910;hs3:57902407-57902407,hs3:115064499-115064499;hs3:57970661-57970661,hs3:97908173-97908173;hs3:57996200-57996200,hs11:72101342-72101342;hs3:58012464-58012464,hs11:100430929-100430929;hs3:58066835-58066835,hs11:132374742-132374742;hs3:58129346-58129346,hs11:57254910-57254910;hs3:58213871-58213871,hs3:58635479-58635479;hs3:58213871-58213871,hs3:58635479-58635479;hs3:58238187-58238187,hs11:19490251-19490251;hs3:58260436-58260436,hs11:106497531-106497531;hs3:58298015-58298015,hs11:120435423-120435423;hs3:58328824-58328824,hs11:41729943-41729943;hs3:58345677-58345677,hs3:123753408-123753408;hs3:58349416-58349416,hs11:13337542-13337542;hs3:58360750-58360750,hs3:105677277-105677277;hs3:58506950-58506950,hs11:70582297-70582297;hs3:58517070-58517070,hs11:487632-487632;hs3:58552909-58552909,hs11:77814356-77814356;hs3:58617344-58617344,hs3:77559765-77559765;hs3:58625931-58625931,hs3:114551290-114551290;hs3:58645027-58645027,hs3:184879745-184879745;hs3:58818784-58818784,hs3:145702150-145702150;hs3:58836107-58836107,hs11:26969895-26969895;hs3:58836446-58836446,hs3:152753823-152753823;hs3:58836525-58836525,hs11:76160021-76160021;hs3:58843552-58843552,hs11:85151744-85151744;hs3:59091035-59091035,hs11:50376029-50376029;hs3:59141830-59141830,hs3:83790596-83790596;hs3:59160951-59160951,hs3:154280167-154280167;hs3:59183579-59183579,hs11:85042561-85042561;hs3:59185539-59185539,hs3:78129046-78129046;hs3:59472058-59472058,hs3:61880157-61880157;hs3:59529831-59529831,hs3:180098681-180098681;hs3:59532825-59532825,hs3:162145473-162145473;hs3:59545472-59545472,hs11:4753245-4753245;hs3:59625711-59625711,hs11:40493727-40493727;hs3:59740866-59740866,hs3:137334880-137334880;hs3:59960242-59960242,hs3:169675605-169675605;hs3:60111091-60111091,hs11:46486053-46486053;hs3:60113859-60113859,hs3:164564224-164564224;hs3:60204060-60204060,hs11:46462334-46462334;hs3:60263903-60263903,hs3:180661934-180661934;hs3:60320384-60320384,hs11:81070505-81070505;hs3:60492275-60492275,hs11:78085276-78085276;hs3:60549422-60549422,hs11:80176279-80176279;hs3:60938516-60938516,hs3:173719597-173719597;hs3:60941934-60941934,hs3:80594659-80594659;hs3:61000962-61000962,hs11:87174065-87174065;hs3:61008780-61008780,hs11:43670731-43670731;hs3:61011531-61011531,hs11:74157237-74157237;hs3:61028809-61028809,hs11:81993368-81993368;hs3:61133969-61133969,hs11:30050040-30050040;hs3:61181269-61181269,hs3:183223529-183223529;hs3:61195995-61195995,hs11:117453778-117453778;hs3:61207408-61207408,hs11:38388319-38388319;hs3:61367502-61367502,hs11:64217809-64217809;hs3:61529265-61529265,hs11:92120656-92120656;hs3:61562931-61562931,hs11:44145321-44145321;hs3:61627853-61627853,hs3:100648832-100648832;hs3:61664432-61664432,hs11:125363221-125363221;hs3:61670829-61670829,hs11:61212505-61212505;hs3:61671236-61671236,hs11:8192727-8192727;hs3:61675073-61675073,hs3:66314691-66314691;hs3:61685797-61685797,hs3:170944051-170944051;hs3:61696728-61696728,hs3:122343816-122343816;hs3:61712494-61712494,hs3:126838336-126838336;hs3:61812867-61812867,hs11:75061541-75061541;hs3:61820431-61820431,hs11:109252594-109252594;hs3:61886389-61886389,hs11:72104531-72104531;hs3:62040687-62040687,hs11:42065134-42065134;hs3:62143592-62143592,hs3:77998936-77998936;hs3:62256578-62256578,hs3:101960097-101960097;hs3:62365278-62365278,hs11:110168649-110168649;hs3:62372846-62372846,hs3:124389954-124389954;hs3:62438239-62438239,hs3:97125255-97125255;hs3:62477266-62477266,hs11:94866760-94866760;hs3:62515534-62515534,hs11:61030098-61030098;hs3:62523621-62523621,hs11:5983658-5983658;hs3:62606364-62606364,hs11:61699193-61699193;hs3:62609062-62609062,hs11:81343829-81343829;hs3:62633456-62633456,hs3:166570637-166570637;hs3:62669103-62669103,hs3:169494900-169494900;hs3:62703262-62703262,hs11:11782535-11782535;hs3:62706901-62706901,hs11:60694361-60694361;hs3:62775172-62775172,hs11:41926021-41926021;hs3:63002941-63002941,hs11:84205549-84205549;hs3:63091375-63091375,hs3:100176496-100176496;hs3:63094046-63094046,hs11:64858483-64858483;hs3:63099413-63099413,hs3:80965164-80965164;hs3:63110528-63110528,hs11:43859032-43859032;hs3:63134939-63134939,hs3:162297196-162297196;hs3:63266035-63266035,hs11:121159034-121159034;hs3:63374103-63374103,hs3:97517078-97517078;hs3:63740048-63740048,hs3:100412326-100412326;hs3:63767730-63767730,hs3:170649443-170649443;hs3:63962110-63962110,hs11:32816077-32816077;hs3:63978510-63978510,hs11:67214074-67214074;hs3:64158582-64158582,hs3:153117770-153117770;hs3:64185461-64185461,hs3:141621139-141621139;hs3:64200242-64200242,hs3:118509597-118509597;hs3:64217720-64217720,hs11:91631820-91631820;hs3:64223590-64223590,hs3:145408257-145408257;hs3:64305333-64305333,hs11:622004-622004;hs3:64345280-64345280,hs11:101345437-101345437;hs3:64355591-64355591,hs3:165005540-165005540;hs3:64527558-64527558,hs3:196050461-196050461;hs3:64655838-64655838,hs3:180668316-180668316;hs3:64699452-64699452,hs11:46111313-46111313;hs3:64759474-64759474,hs11:105298541-105298541;hs3:64765950-64765950,hs3:168313916-168313916;hs3:64780427-64780427,hs11:55237213-55237213;hs3:64915233-64915233,hs11:132354661-132354661;hs3:65024154-65024154,hs3:84798860-84798860;hs3:65034832-65034832,hs3:127894242-127894242;hs3:65050105-65050105,hs3:136375189-136375189;hs3:65117945-65117945,hs11:96962418-96962418;hs3:65133319-65133319,hs3:73861151-73861151;hs3:65209901-65209901,hs3:134799530-134799530;hs3:65257835-65257835,hs3:157884757-157884757;hs3:65356248-65356248,hs3:135226906-135226906;hs3:65373449-65373449,hs3:65374683-65374683;hs3:65384201-65384201,hs11:68699148-68699148;hs3:65422227-65422227,hs11:62636129-62636129;hs3:65518419-65518419,hs3:109878329-109878329;hs3:65624906-65624906,hs11:85950912-85950912;hs3:65674138-65674138,hs11:6728748-6728748;hs3:65695231-65695231,hs11:110916876-110916876;hs3:65774039-65774039,hs3:196503271-196503271;hs3:65793090-65793090,hs11:65350401-65350401;hs3:65837848-65837848,hs3:182015567-182015567;hs3:65839610-65839610,hs3:104254108-104254108;hs3:65846833-65846833,hs3:121915462-121915462;hs3:65855397-65855397,hs11:35047629-35047629;hs3:65959364-65959364,hs11:11857301-11857301;hs3:65973789-65973789,hs11:71683154-71683154;hs3:65977134-65977134,hs11:80474231-80474231;hs3:66024940-66024940,hs11:129404371-129404371;hs3:66028305-66028305,hs11:93095576-93095576;hs3:66028305-66028305,hs11:93095576-93095576;hs3:66142867-66142867,hs3:144147671-144147671;hs3:66144854-66144854,hs3:140498789-140498789;hs3:66288566-66288566,hs11:113618671-113618671;hs3:66371642-66371642,hs3:144618915-144618915;hs3:66424426-66424426,hs3:72208123-72208123;hs3:66455795-66455795,hs3:152649170-152649170;hs3:66461135-66461135,hs11:94409812-94409812;hs3:66477328-66477328,hs11:67931145-67931145;hs3:66486316-66486316,hs3:185653260-185653260;hs3:66489072-66489072,hs11:116074385-116074385;hs3:66549848-66549848,hs3:95258024-95258024;hs3:66549982-66549982,hs3:71438598-71438598;hs3:66554271-66554271,hs11:93321786-93321786;hs3:66688448-66688448,hs11:45908078-45908078;hs3:66725751-66725751,hs3:104542110-104542110;hs3:67065602-67065602,hs3:128433703-128433703;hs3:67115524-67115524,hs11:92452313-92452313;hs3:67120849-67120849,hs3:75409570-75409570;hs3:67163121-67163121,hs11:46063336-46063336;hs3:67236425-67236425,hs11:118927222-118927222;hs3:67295700-67295700,hs3:122550021-122550021;hs3:67411009-67411009,hs3:148996982-148996982;hs3:67537328-67537328,hs11:60055974-60055974;hs3:67779925-67779925,hs11:104185144-104185144;hs3:67783189-67783189,hs11:50447938-50447938;hs3:67786809-67786809,hs3:103588645-103588645;hs3:68019099-68019099,hs3:150876267-150876267;hs3:68030398-68030398,hs3:151027915-151027915;hs3:68175072-68175072,hs11:3844034-3844034;hs3:68269698-68269698,hs11:33117070-33117070;hs3:68299034-68299034,hs3:162870853-162870853;hs3:68481216-68481216,hs11:40612742-40612742;hs3:68522823-68522823,hs11:69431396-69431396;hs3:68750024-68750024,hs11:21792494-21792494;hs3:68802869-68802869,hs3:178532126-178532126;hs3:68807005-68807005,hs3:149663629-149663629;hs3:68807005-68807005,hs3:149663629-149663629;hs3:68828265-68828265,hs11:87335009-87335009;hs3:68931263-68931263,hs11:43578762-43578762;hs3:69010253-69010253,hs11:126209068-126209068;hs3:69055456-69055456,hs3:87388219-87388219;hs3:69168520-69168520,hs3:144567346-144567346;hs3:69180945-69180945,hs11:77602747-77602747;hs3:69186923-69186923,hs11:3194573-3194573;hs3:69278115-69278115,hs3:161731794-161731794;hs3:69317682-69317682,hs11:112858010-112858010;hs3:69331687-69331687,hs11:117014936-117014936;hs3:69389018-69389018,hs3:105171904-105171904;hs3:69396996-69396996,hs3:77528206-77528206;hs3:69669356-69669356,hs11:27397997-27397997;hs3:69731233-69731233,hs11:93444062-93444062;hs3:69735567-69735567,hs11:43733695-43733695;hs3:69758278-69758278,hs3:115084726-115084726;hs3:69762343-69762343,hs3:136581332-136581332;hs3:69946804-69946804,hs3:183016034-183016034;hs3:69968782-69968782,hs3:183308067-183308067;hs3:69969570-69969570,hs11:99225701-99225701;hs3:70035377-70035377,hs3:190250309-190250309;hs3:70045163-70045163,hs11:93271786-93271786;hs3:70088606-70088606,hs3:191971514-191971514;hs3:70331502-70331502,hs11:35180216-35180216;hs3:70417835-70417835,hs11:123440331-123440331;hs3:70557006-70557006,hs11:56158397-56158397;hs3:70558861-70558861,hs11:130569698-130569698;hs3:70605879-70605879,hs3:75463472-75463472;hs3:70900420-70900420,hs3:172510733-172510733;hs3:70901575-70901575,hs3:116580532-116580532;hs3:70910506-70910506,hs3:101297539-101297539;hs3:71289398-71289398,hs3:195564828-195564828;hs3:71321717-71321717,hs11:113867097-113867097;hs3:71325806-71325806,hs11:112398837-112398837;hs3:71427106-71427106,hs11:42230805-42230805;hs3:71438448-71438448,hs3:160753588-160753588;hs3:71446138-71446138,hs11:38263643-38263643;hs3:71640653-71640653,hs11:64147077-64147077;hs3:71647206-71647206,hs3:143627974-143627974;hs3:71745153-71745153,hs3:133042136-133042136;hs3:71750159-71750159,hs3:191457163-191457163;hs3:71753656-71753656,hs11:121033140-121033140;hs3:71769844-71769844,hs3:101583292-101583292;hs3:71780555-71780555,hs3:158449667-158449667;hs3:71799540-71799540,hs11:92450119-92450119;hs3:71802983-71802983,hs11:66493435-66493435;hs3:71834227-71834227,hs3:133589894-133589894;hs3:71860789-71860789,hs11:91349333-91349333;hs3:71968318-71968318,hs11:73801129-73801129;hs3:72289937-72289937,hs11:25236640-25236640;hs3:72411260-72411260,hs11:9013861-9013861;hs3:72436034-72436034,hs3:183958851-183958851;hs3:72461560-72461560,hs11:98227367-98227367;hs3:72712690-72712690,hs3:196109727-196109727;hs3:72791305-72791305,hs3:80832544-80832544;hs3:73114720-73114720,hs11:42722341-42722341;hs3:73127530-73127530,hs3:103953128-103953128;hs3:73131979-73131979,hs11:67805185-67805185;hs3:73144798-73144798,hs3:149573093-149573093;hs3:73183913-73183913,hs11:115952349-115952349;hs3:73186527-73186527,hs11:129844357-129844357;hs3:73217482-73217482,hs11:16368519-16368519;hs3:73219851-73219851,hs3:89441152-89441152;hs3:73240605-73240605,hs3:196050719-196050719;hs3:73412608-73412608,hs11:97248357-97248357;hs3:73501568-73501568,hs3:117496319-117496319;hs3:73543138-73543138,hs3:76025265-76025265;hs3:73595244-73595244,hs3:151068176-151068176;hs3:73651704-73651704,hs3:176755791-176755791;hs3:73801029-73801029,hs3:119384026-119384026;hs3:73814295-73814295,hs11:68948089-68948089;hs3:73849565-73849565,hs11:74824252-74824252;hs3:73917911-73917911,hs11:36332228-36332228;hs3:73974576-73974576,hs11:46096084-46096084;hs3:73981946-73981946,hs3:83323556-83323556;hs3:73988515-73988515,hs11:32771635-32771635;hs3:73999673-73999673,hs11:42063118-42063118;hs3:74005918-74005918,hs11:96744287-96744287;hs3:74015876-74015876,hs11:27700809-27700809;hs3:74090694-74090694,hs3:196284296-196284296;hs3:74116117-74116117,hs3:90281429-90281429;hs3:74171835-74171835,hs3:175857366-175857366;hs3:74293641-74293641,hs11:30319205-30319205;hs3:74296619-74296619,hs11:62668698-62668698;hs3:74310800-74310800,hs11:25632313-25632313;hs3:74966760-74966760,hs3:131476747-131476747;hs3:74984562-74984562,hs11:87215007-87215007;hs3:74989604-74989604,hs11:8746347-8746347;hs3:75181628-75181628,hs11:57039300-57039300;hs3:75404932-75404932,hs11:124193159-124193159;hs3:75411387-75411387,hs3:135169447-135169447;hs3:75602531-75602531,hs3:171665715-171665715;hs3:75915340-75915340,hs3:193537936-193537936;hs3:75933833-75933833,hs3:147657717-147657717;hs3:76656673-76656673,hs11:98339972-98339972;hs3:76884680-76884680,hs3:113343128-113343128;hs3:76888137-76888137,hs11:95768314-95768314;hs3:76892324-76892324,hs11:112853371-112853371;hs3:76900651-76900651,hs11:115923397-115923397;hs3:76907166-76907166,hs3:142396118-142396118;hs3:77118994-77118994,hs11:114630969-114630969;hs3:77207229-77207229,hs11:48703910-48703910;hs3:77231506-77231506,hs11:83216665-83216665;hs3:77232622-77232622,hs11:111385273-111385273;hs3:77273534-77273534,hs11:126123752-126123752;hs3:77377975-77377975,hs3:112650741-112650741;hs3:77556715-77556715,hs11:115112125-115112125;hs3:77612707-77612707,hs11:114017091-114017091;hs3:77616030-77616030,hs3:93799630-93799630;hs3:77645085-77645085,hs11:74098612-74098612;hs3:77780954-77780954,hs3:144141704-144141704;hs3:77994090-77994090,hs11:96178728-96178728;hs3:78196319-78196319,hs3:100710396-100710396;hs3:78226142-78226142,hs11:55187353-55187353;hs3:78547497-78547497,hs11:76271587-76271587;hs3:78581314-78581314,hs3:82421801-82421801;hs3:78583664-78583664,hs11:50551139-50551139;hs3:78919636-78919636,hs11:83163263-83163263;hs3:78935957-78935957,hs11:30337138-30337138;hs3:79026930-79026930,hs3:116586369-116586369;hs3:79044203-79044203,hs11:44941969-44941969;hs3:79083355-79083355,hs3:132592362-132592362;hs3:79092099-79092099,hs3:174388031-174388031;hs3:79758682-79758682,hs11:14440094-14440094;hs3:79762205-79762205,hs11:122702041-122702041;hs3:79809645-79809645,hs11:115810887-115810887;hs3:79812854-79812854,hs11:12524296-12524296;hs3:79936680-79936680,hs3:170261092-170261092;hs3:80036439-80036439,hs11:81442951-81442951;hs3:80055061-80055061,hs11:50125877-50125877;hs3:80097059-80097059,hs3:177963622-177963622;hs3:80230966-80230966,hs11:109875946-109875946;hs3:80293322-80293322,hs3:89682820-89682820;hs3:80572937-80572937,hs11:113788134-113788134;hs3:80597207-80597207,hs3:181740674-181740674;hs3:80650968-80650968,hs3:110588738-110588738;hs3:80845168-80845168,hs3:171210747-171210747;hs3:80874579-80874579,hs3:82748800-82748800;hs3:80902390-80902390,hs11:63474279-63474279;hs3:80965958-80965958,hs11:132113772-132113772;hs3:81031363-81031363,hs3:89781750-89781750;hs3:81039063-81039063,hs3:93975185-93975185;hs3:81299352-81299352,hs3:188162153-188162153;hs3:81362606-81362606,hs3:153097789-153097789;hs3:81584282-81584282,hs3:99804066-99804066;hs3:81675460-81675460,hs3:100175212-100175212;hs3:81757006-81757006,hs11:113148901-113148901;hs3:81783650-81783650,hs3:145706074-145706074;hs3:82067907-82067907,hs11:59294193-59294193;hs3:82201602-82201602,hs3:166727050-166727050;hs3:82378923-82378923,hs3:160464691-160464691;hs3:82404766-82404766,hs3:176883279-176883279;hs3:82429980-82429980,hs11:103575988-103575988;hs3:82547489-82547489,hs11:89109741-89109741;hs3:82596416-82596416,hs11:65370985-65370985;hs3:82887958-82887958,hs11:27942215-27942215;hs3:82908373-82908373,hs3:108330588-108330588;hs3:83046048-83046048,hs3:124949789-124949789;hs3:83072992-83072992,hs3:95268153-95268153;hs3:83389422-83389422,hs11:123468571-123468571;hs3:83613953-83613953,hs3:192352719-192352719;hs3:83767103-83767103,hs3:112387946-112387946;hs3:83966236-83966236,hs11:55378715-55378715;hs3:84188910-84188910,hs11:107383250-107383250;hs3:84373295-84373295,hs11:24562535-24562535;hs3:84411607-84411607,hs11:81282378-81282378;hs3:84424537-84424537,hs3:113492281-113492281;hs3:84440245-84440245,hs11:79978095-79978095;hs3:84775773-84775773,hs3:108295712-108295712;hs3:84810037-84810037,hs11:5669811-5669811;hs3:84814283-84814283,hs11:9620929-9620929;hs3:84917170-84917170,hs3:107281627-107281627;hs3:84980823-84980823,hs11:47055826-47055826;hs3:85156379-85156379,hs3:150763711-150763711;hs3:85161894-85161894,hs11:68808575-68808575;hs3:85204662-85204662,hs3:134844706-134844706;hs3:85278101-85278101,hs11:45485829-45485829;hs3:85303963-85303963,hs11:120162718-120162718;hs3:85514803-85514803,hs11:86024989-86024989;hs3:85536264-85536264,hs11:8177031-8177031;hs3:85567226-85567226,hs3:170666908-170666908;hs3:85656724-85656724,hs3:105319583-105319583;hs3:85668148-85668148,hs3:175745443-175745443;hs3:85707740-85707740,hs3:146749043-146749043;hs3:85710723-85710723,hs11:63331035-63331035;hs3:85976144-85976144,hs3:169836420-169836420;hs3:86072633-86072633,hs11:48140071-48140071;hs3:86288511-86288511,hs11:78754353-78754353;hs3:86307833-86307833,hs3:184972951-184972951;hs3:86314903-86314903,hs11:105897130-105897130;hs3:86323238-86323238,hs3:123882064-123882064;hs3:86338777-86338777,hs3:136214093-136214093;hs3:86345948-86345948,hs3:107383943-107383943;hs3:86348181-86348181,hs11:88791308-88791308;hs3:86351529-86351529,hs11:17538509-17538509;hs3:86379257-86379257,hs3:189205862-189205862;hs3:86650167-86650167,hs3:180003749-180003749;hs3:86781547-86781547,hs3:176259584-176259584;hs3:86888033-86888033,hs11:46711353-46711353;hs3:86892077-86892077,hs3:137168962-137168962;hs3:86913197-86913197,hs11:22664259-22664259;hs3:86972135-86972135,hs11:73032671-73032671;hs3:86985609-86985609,hs3:103088709-103088709;hs3:87059164-87059164,hs11:99224471-99224471;hs3:87348687-87348687,hs3:187168892-187168892;hs3:87378999-87378999,hs11:17613029-17613029;hs3:87473153-87473153,hs3:104347509-104347509;hs3:87474860-87474860,hs11:40968703-40968703;hs3:87599796-87599796,hs3:161799917-161799917;hs3:87621361-87621361,hs3:99096153-99096153;hs3:87746631-87746631,hs11:55436606-55436606;hs3:87969266-87969266,hs11:110786463-110786463;hs3:88001788-88001788,hs3:135149903-135149903;hs3:88628766-88628766,hs3:183246042-183246042;hs3:88640590-88640590,hs3:161968260-161968260;hs3:88756271-88756271,hs11:3146966-3146966;hs3:88860504-88860504,hs3:98284849-98284849;hs3:89012789-89012789,hs3:183444827-183444827;hs3:89260658-89260658,hs11:133691094-133691094;hs3:89384997-89384997,hs11:76307051-76307051;hs3:89408922-89408922,hs3:170959473-170959473;hs3:89418144-89418144,hs3:157088081-157088081;hs3:89487635-89487635,hs3:153416121-153416121;hs3:89497229-89497229,hs11:72547378-72547378;hs3:89506967-89506967,hs11:74966258-74966258;hs3:89508688-89508688,hs11:5191994-5191994;hs3:89621081-89621081,hs3:177954721-177954721;hs3:89686309-89686309,hs3:100857100-100857100;hs3:89976763-89976763,hs11:28469938-28469938;hs3:90083491-90083491,hs3:131313092-131313092;hs3:90108419-90108419,hs3:93981318-93981318;hs3:90130256-90130256,hs11:81234245-81234245;hs3:90145080-90145080,hs11:46101856-46101856;hs3:93805680-93805680,hs3:162024254-162024254;hs3:93948441-93948441,hs11:55125163-55125163;hs3:93950993-93950993,hs11:19746776-19746776;hs3:93983734-93983734,hs11:117704601-117704601;hs3:93985280-93985280,hs11:44967664-44967664;hs3:94020423-94020423,hs3:97164790-97164790;hs3:94250154-94250154,hs11:127838713-127838713;hs3:94931350-94931350,hs11:27814471-27814471;hs3:95010114-95010114,hs3:125555230-125555230;hs3:95040611-95040611,hs3:119549820-119549820;hs3:95223872-95223872,hs11:80539786-80539786;hs3:95223871-95223871,hs11:80539786-80539786;hs3:95226549-95226549,hs3:181536587-181536587;hs3:95290492-95290492,hs11:119035378-119035378;hs3:95462381-95462381,hs11:92341527-92341527;hs3:95521370-95521370,hs3:182813092-182813092;hs3:95563813-95563813,hs11:100689564-100689564;hs3:95717955-95717955,hs3:136692439-136692439;hs3:95760232-95760232,hs11:50486402-50486402;hs3:95777188-95777188,hs3:121900251-121900251;hs3:95782937-95782937,hs3:128796678-128796678;hs3:95785163-95785163,hs11:129717208-129717208;hs3:95790200-95790200,hs3:182779406-182779406;hs3:95864137-95864137,hs11:16297935-16297935;hs3:95868311-95868311,hs3:140313064-140313064;hs3:95888698-95888698,hs3:128287230-128287230;hs3:95896686-95896686,hs11:45518922-45518922;hs3:95994575-95994575,hs3:106266816-106266816;hs3:95998822-95998822,hs11:113970928-113970928;hs3:96228845-96228845,hs3:143453367-143453367;hs3:96308894-96308894,hs11:5025690-5025690;hs3:96337282-96337282,hs3:103097718-103097718;hs3:96370787-96370787,hs11:62969750-62969750;hs3:96803213-96803213,hs11:15798662-15798662;hs3:96824738-96824738,hs11:113619876-113619876;hs3:96826006-96826006,hs11:8340595-8340595;hs3:96974045-96974045,hs11:128304007-128304007;hs3:97115780-97115780,hs11:5190972-5190972;hs3:97284803-97284803,hs11:7007573-7007573;hs3:97339766-97339766,hs11:67443637-67443637;hs3:97347204-97347204,hs3:117485106-117485106;hs3:97365115-97365115,hs3:118986624-118986624;hs3:97405434-97405434,hs11:16328940-16328940;hs3:97449337-97449337,hs11:64186017-64186017;hs3:97557324-97557324,hs3:153406928-153406928;hs3:97635693-97635693,hs11:23996360-23996360;hs3:97661591-97661591,hs11:45305184-45305184;hs3:97671187-97671187,hs11:65377979-65377979;hs3:97674331-97674331,hs11:134492823-134492823;hs3:97758014-97758014,hs3:102250693-102250693;hs3:97808318-97808318,hs3:190797903-190797903;hs3:97941996-97941996,hs3:166808191-166808191;hs3:98107925-98107925,hs3:130293323-130293323;hs3:98158083-98158083,hs11:67082775-67082775;hs3:98326864-98326864,hs3:140115191-140115191;hs3:98660248-98660248,hs3:142449318-142449318;hs3:98855635-98855635,hs3:189075548-189075548;hs3:98913693-98913693,hs3:195308801-195308801;hs3:98923503-98923503,hs11:76075615-76075615;hs3:98928884-98928884,hs3:176796978-176796978;hs3:99120627-99120627,hs11:89152116-89152116;hs3:99125201-99125201,hs3:161926233-161926233;hs3:99290158-99290158,hs11:1548285-1548285;hs3:99515916-99515916,hs3:166205206-166205206;hs3:99527203-99527203,hs11:114599037-114599037;hs3:99626861-99626861,hs3:119931464-119931464;hs3:99651720-99651720,hs3:164665759-164665759;hs3:99652205-99652205,hs11:13396071-13396071;hs3:99657500-99657500,hs11:127428437-127428437;hs3:99663527-99663527,hs3:168122697-168122697;hs3:99699871-99699871,hs11:41285480-41285480;hs3:99707748-99707748,hs3:114003258-114003258;hs3:99761739-99761739,hs11:72422996-72422996;hs3:99765507-99765507,hs11:22394343-22394343;hs3:99846617-99846617,hs3:160024288-160024288;hs3:99964174-99964174,hs3:135685331-135685331;hs3:100046162-100046162,hs3:134521299-134521299;hs3:100094389-100094389,hs11:81936104-81936104;hs3:100108169-100108169,hs11:84651466-84651466;hs3:100161690-100161690,hs3:138525782-138525782;hs3:100183386-100183386,hs3:112174510-112174510;hs3:100344381-100344381,hs3:123756767-123756767;hs3:100366657-100366657,hs3:196936831-196936831;hs3:100367490-100367490,hs11:99894031-99894031;hs3:100367489-100367489,hs11:99894031-99894031;hs3:100377287-100377287,hs3:193063037-193063037;hs3:100383716-100383716,hs3:153376493-153376493;hs3:100418988-100418988,hs3:176378011-176378011;hs3:100426017-100426017,hs11:98106956-98106956;hs3:100582313-100582313,hs11:34475969-34475969;hs3:100753380-100753380,hs3:162241528-162241528;hs3:100900512-100900512,hs3:166712226-166712226;hs3:101323741-101323741,hs11:83887578-83887578;hs3:101368731-101368731,hs11:22635838-22635838;hs3:101372815-101372815,hs11:66641998-66641998;hs3:101376344-101376344,hs3:126264200-126264200;hs3:101389033-101389033,hs3:121736872-121736872;hs3:101413687-101413687,hs11:122666607-122666607;hs3:101421477-101421477,hs11:98697982-98697982;hs3:101431408-101431408,hs11:43696717-43696717;hs3:101457119-101457119,hs3:144082025-144082025;hs3:101530140-101530140,hs11:57342280-57342280;hs3:101567045-101567045,hs11:80454761-80454761;hs3:101663459-101663459,hs11:107436051-107436051;hs3:101898025-101898025,hs3:197323184-197323184;hs3:101947593-101947593,hs3:164677948-164677948;hs3:101965207-101965207,hs3:128458214-128458214;hs3:101971383-101971383,hs3:177477825-177477825;hs3:102200319-102200319,hs11:8155713-8155713;hs3:102207528-102207528,hs3:112155412-112155412;hs3:102396262-102396262,hs3:167619716-167619716;hs3:102500085-102500085,hs3:188275669-188275669;hs3:102503278-102503278,hs11:125866725-125866725;hs3:102588785-102588785,hs3:189055486-189055486;hs3:103047600-103047600,hs11:106879473-106879473;hs3:103083316-103083316,hs3:194493645-194493645;hs3:103537421-103537421,hs11:38265154-38265154;hs3:103579600-103579600,hs11:45345039-45345039;hs3:103702969-103702969,hs3:133217582-133217582;hs3:103984339-103984339,hs11:111379904-111379904;hs3:103991345-103991345,hs3:162685495-162685495;hs3:104176293-104176293,hs3:147347610-147347610;hs3:104281690-104281690,hs11:82990969-82990969;hs3:104283170-104283170,hs3:105159255-105159255;hs3:104297106-104297106,hs11:28873379-28873379;hs3:104318720-104318720,hs11:55639477-55639477;hs3:104319782-104319782,hs3:130732625-130732625;hs3:104353016-104353016,hs3:115758798-115758798;hs3:104507153-104507153,hs3:136539064-136539064;hs3:104548469-104548469,hs3:168011566-168011566;hs3:104589878-104589878,hs3:157219340-157219340;hs3:104601332-104601332,hs3:168010960-168010960;hs3:104871808-104871808,hs3:144807311-144807311;hs3:105070656-105070656,hs11:14448590-14448590;hs3:105078993-105078993,hs11:93747284-93747284;hs3:105129379-105129379,hs11:72607664-72607664;hs3:105224820-105224820,hs3:195762343-195762343;hs3:105231930-105231930,hs3:108860243-108860243;hs3:105398019-105398019,hs11:85366454-85366454;hs3:105506597-105506597,hs11:64855770-64855770;hs3:105524488-105524488,hs11:86774858-86774858;hs3:105571327-105571327,hs3:189391836-189391836;hs3:105644353-105644353,hs3:119279665-119279665;hs3:105651750-105651750,hs11:16361408-16361408;hs3:105741238-105741238,hs11:28932443-28932443;hs3:106147321-106147321,hs11:73449886-73449886;hs3:106157978-106157978,hs11:110519704-110519704;hs3:106194220-106194220,hs11:103693270-103693270;hs3:106438494-106438494,hs3:133584927-133584927;hs3:106470600-106470600,hs11:83112147-83112147;hs3:106550049-106550049,hs11:30218068-30218068;hs3:106720175-106720175,hs3:148786930-148786930;hs3:106856561-106856561,hs3:132054363-132054363;hs3:106913515-106913515,hs3:156625077-156625077;hs3:106960204-106960204,hs11:41505280-41505280;hs3:106976913-106976913,hs3:180627674-180627674;hs3:107220056-107220056,hs3:187581075-187581075;hs3:107369220-107369220,hs11:17784666-17784666;hs3:107486738-107486738,hs11:16972477-16972477;hs3:107487843-107487843,hs11:75285422-75285422;hs3:107553036-107553036,hs3:188415132-188415132;hs3:107556775-107556775,hs3:134111690-134111690;hs3:107560149-107560149,hs3:195652181-195652181;hs3:107621166-107621166,hs3:151936214-151936214;hs3:107792674-107792674,hs3:118862128-118862128;hs3:107794987-107794987,hs3:133381733-133381733;hs3:107804485-107804485,hs11:113370811-113370811;hs3:107822567-107822567,hs11:75902735-75902735;hs3:107859600-107859600,hs11:104345053-104345053;hs3:107863152-107863152,hs11:15260682-15260682;hs3:107864879-107864879,hs11:44967243-44967243;hs3:107864773-107864773,hs11:8128464-8128464;hs3:107871007-107871007,hs11:47069958-47069958;hs3:108057051-108057051,hs3:184575475-184575475;hs3:108202231-108202231,hs11:20365579-20365579;hs3:108263704-108263704,hs3:184638753-184638753;hs3:108274616-108274616,hs3:180444418-180444418;hs3:108578295-108578295,hs3:124015894-124015894;hs3:108764640-108764640,hs3:182065047-182065047;hs3:108847376-108847376,hs3:115117281-115117281;hs3:108854911-108854911,hs11:125399531-125399531;hs3:108865365-108865365,hs11:49241737-49241737;hs3:109358209-109358209,hs11:128444977-128444977;hs3:109425156-109425156,hs3:143420375-143420375;hs3:109483414-109483414,hs3:184381576-184381576;hs3:109605762-109605762,hs11:114013797-114013797;hs3:109606729-109606729,hs3:131018251-131018251;hs3:109760686-109760686,hs11:64160966-64160966;hs3:109789720-109789720,hs11:124313476-124313476;hs3:109828007-109828007,hs11:12024919-12024919;hs3:109868081-109868081,hs3:127337866-127337866;hs3:109982618-109982618,hs3:119026242-119026242;hs3:110038525-110038525,hs11:71051470-71051470;hs3:110122590-110122590,hs3:160619509-160619509;hs3:110129488-110129488,hs3:189444022-189444022;hs3:110148670-110148670,hs11:129100481-129100481;hs3:110157694-110157694,hs11:21359030-21359030;hs3:110393950-110393950,hs3:126254026-126254026;hs3:110449328-110449328,hs11:20721044-20721044;hs3:110724383-110724383,hs3:149454014-149454014;hs3:110727102-110727102,hs11:62220816-62220816;hs3:111092590-111092590,hs11:42418611-42418611;hs3:111095505-111095505,hs11:86882834-86882834;hs3:111111620-111111620,hs11:93764285-93764285;hs3:111116256-111116256,hs11:55359722-55359722;hs3:111378215-111378215,hs3:129060089-129060089;hs3:111382006-111382006,hs11:19181412-19181412;hs3:111426262-111426262,hs11:40605745-40605745;hs3:111469937-111469937,hs11:80128165-80128165;hs3:111472415-111472415,hs11:48613412-48613412;hs3:111525104-111525104,hs3:175164124-175164124;hs3:111542750-111542750,hs3:164578831-164578831;hs3:111579846-111579846,hs11:86547324-86547324;hs3:111821232-111821232,hs11:82800416-82800416;hs3:111821993-111821993,hs11:60622397-60622397;hs3:111821994-111821994,hs11:60622398-60622398;hs3:111839607-111839607,hs11:85486585-85486585;hs3:112182245-112182245,hs11:68187338-68187338;hs3:112275137-112275137,hs11:61188050-61188050;hs3:112373607-112373607,hs11:83309864-83309864;hs3:112398063-112398063,hs11:107408201-107408201;hs3:112504515-112504515,hs11:83055103-83055103;hs3:112518581-112518581,hs11:108010966-108010966;hs3:112595115-112595115,hs11:93912859-93912859;hs3:112602371-112602371,hs3:168287627-168287627;hs3:112626209-112626209,hs3:163067144-163067144;hs3:112806973-112806973,hs3:144207959-144207959;hs3:112808168-112808168,hs3:184119731-184119731;hs3:113173613-113173613,hs11:14429371-14429371;hs3:113379981-113379981,hs3:158451864-158451864;hs3:113411265-113411265,hs11:14431192-14431192;hs3:113448631-113448631,hs11:92527909-92527909;hs3:113457889-113457889,hs11:20024115-20024115;hs3:113472653-113472653,hs3:132768407-132768407;hs3:113643526-113643526,hs11:49236448-49236448;hs3:113667562-113667562,hs11:109970223-109970223;hs3:113866150-113866150,hs3:123692390-123692390;hs3:114112251-114112251,hs11:31784311-31784311;hs3:114335764-114335764,hs3:188784633-188784633;hs3:114363071-114363071,hs11:48943667-48943667;hs3:114366501-114366501,hs3:142682118-142682118;hs3:114455927-114455927,hs11:111549595-111549595;hs3:114475283-114475283,hs11:50341424-50341424;hs3:114485528-114485528,hs11:76170081-76170081;hs3:114489764-114489764,hs11:83581475-83581475;hs3:114520844-114520844,hs11:3697026-3697026;hs3:114904003-114904003,hs3:195241637-195241637;hs3:115008453-115008453,hs11:23805543-23805543;hs3:115091316-115091316,hs3:118114286-118114286;hs3:115093056-115093056,hs3:120141161-120141161;hs3:115219190-115219190,hs11:9612322-9612322;hs3:115753252-115753252,hs11:65052257-65052257;hs3:115771781-115771781,hs3:194481581-194481581;hs3:115786713-115786713,hs11:68892855-68892855;hs3:115967050-115967050,hs11:101183281-101183281;hs3:116014311-116014311,hs11:113346453-113346453;hs3:116016953-116016953,hs3:148414598-148414598;hs3:116287717-116287717,hs3:142972147-142972147;hs3:116349533-116349533,hs3:151753724-151753724;hs3:116501102-116501102,hs11:30568335-30568335;hs3:116535234-116535234,hs3:154291369-154291369;hs3:116550267-116550267,hs11:100559521-100559521;hs3:116611240-116611240,hs11:130345354-130345354;hs3:116627609-116627609,hs11:32613926-32613926;hs3:116633940-116633940,hs3:164737569-164737569;hs3:117002904-117002904,hs3:132329619-132329619;hs3:117050066-117050066,hs3:138502148-138502148;hs3:117073320-117073320,hs11:44943658-44943658;hs3:117172060-117172060,hs11:115451955-115451955;hs3:117281673-117281673,hs3:119178057-119178057;hs3:117338477-117338477,hs3:125854028-125854028;hs3:117347658-117347658,hs3:149530641-149530641;hs3:117872665-117872665,hs11:74271301-74271301;hs3:118139612-118139612,hs11:73649404-73649404;hs3:118141329-118141329,hs11:114583223-114583223;hs3:118506583-118506583,hs3:166063730-166063730;hs3:118710421-118710421,hs3:173966385-173966385;hs3:118760665-118760665,hs11:26868545-26868545;hs3:118762300-118762300,hs3:167605000-167605000;hs3:118858378-118858378,hs11:23659188-23659188;hs3:118945634-118945634,hs11:126141990-126141990;hs3:118971902-118971902,hs3:149298468-149298468;hs3:119014449-119014449,hs11:25974120-25974120;hs3:119018397-119018397,hs11:16910516-16910516;hs3:119093008-119093008,hs3:136614339-136614339;hs3:119097171-119097171,hs3:152667928-152667928;hs3:119128346-119128346,hs3:193473844-193473844;hs3:119143773-119143773,hs11:37142111-37142111;hs3:119288310-119288310,hs3:128054065-128054065;hs3:119303676-119303676,hs11:133591069-133591069;hs3:119316787-119316787,hs3:139625930-139625930;hs3:119323011-119323011,hs3:193305215-193305215;hs3:119370499-119370499,hs3:144588495-144588495;hs3:119384522-119384522,hs11:65344630-65344630;hs3:119447718-119447718,hs11:128186662-128186662;hs3:119528427-119528427,hs11:14747099-14747099;hs3:119556738-119556738,hs3:179358065-179358065;hs3:119630101-119630101,hs11:133787092-133787092;hs3:119638996-119638996,hs11:12936892-12936892;hs3:119642322-119642322,hs11:84115613-84115613;hs3:119665733-119665733,hs11:12057325-12057325;hs3:119677679-119677679,hs3:176262016-176262016;hs3:119927548-119927548,hs3:171004152-171004152;hs3:119932276-119932276,hs3:170645663-170645663;hs3:119933289-119933289,hs11:74024761-74024761;hs3:119933868-119933868,hs3:163223305-163223305;hs3:120042533-120042533,hs11:132576058-132576058;hs3:120465530-120465530,hs11:41563878-41563878;hs3:120591400-120591400,hs11:25155941-25155941;hs3:120597258-120597258,hs3:188790152-188790152;hs3:120709677-120709677,hs3:184604932-184604932;hs3:120719582-120719582,hs11:110125494-110125494;hs3:120825909-120825909,hs11:798906-798906;hs3:120831023-120831023,hs11:96259290-96259290;hs3:120843774-120843774,hs11:62406171-62406171;hs3:121026123-121026123,hs11:118730012-118730012;hs3:121030068-121030068,hs11:6503869-6503869;hs3:121088052-121088052,hs3:158908637-158908637;hs3:121105635-121105635,hs11:71601147-71601147;hs3:121544026-121544026,hs3:159945300-159945300;hs3:121750708-121750708,hs11:64854323-64854323;hs3:121752286-121752286,hs11:23539944-23539944;hs3:121783609-121783609,hs11:93558446-93558446;hs3:121787141-121787141,hs3:177154611-177154611;hs3:121903347-121903347,hs11:29547957-29547957;hs3:121910782-121910782,hs11:49135391-49135391;hs3:121941130-121941130,hs3:186046790-186046790;hs3:121958298-121958298,hs11:13805613-13805613;hs3:122008528-122008528,hs11:42699571-42699571;hs3:122081816-122081816,hs3:126860592-126860592;hs3:122310613-122310613,hs3:125800573-125800573;hs3:122310690-122310690,hs3:156285963-156285963;hs3:122332068-122332068,hs3:175830433-175830433;hs3:122355281-122355281,hs11:112831644-112831644;hs3:122363976-122363976,hs3:138449568-138449568;hs3:122382812-122382812,hs11:108882079-108882079;hs3:122390392-122390392,hs11:118489053-118489053;hs3:122472479-122472479,hs3:133395580-133395580;hs3:122571947-122571947,hs3:155541613-155541613;hs3:122584239-122584239,hs11:117109014-117109014;hs3:122604836-122604836,hs3:161976578-161976578;hs3:122771781-122771781,hs11:80248069-80248069;hs3:122816855-122816855,hs11:96047973-96047973;hs3:122861580-122861580,hs11:59617272-59617272;hs3:122869066-122869066,hs3:179330522-179330522;hs3:122936692-122936692,hs11:9012181-9012181;hs3:122986729-122986729,hs11:110180897-110180897;hs3:122998223-122998223,hs11:106498022-106498022;hs3:123011979-123011979,hs11:90752605-90752605;hs3:123098227-123098227,hs11:104642077-104642077;hs3:123102037-123102037,hs3:148549379-148549379;hs3:123126626-123126626,hs11:103251447-103251447;hs3:123130959-123130959,hs11:115921267-115921267;hs3:123298320-123298320,hs11:120176631-120176631;hs3:123298957-123298957,hs3:125865741-125865741;hs3:123323400-123323400,hs11:117350315-117350315;hs3:123323232-123323232,hs11:31634341-31634341;hs3:123323231-123323231,hs11:31634341-31634341;hs3:123465047-123465047,hs11:130976959-130976959;hs3:123465905-123465905,hs11:6511940-6511940;hs3:123617833-123617833,hs3:188295707-188295707;hs3:123644013-123644013,hs11:119350264-119350264;hs3:123659098-123659098,hs3:150751841-150751841;hs3:123675946-123675946,hs11:41680964-41680964;hs3:123795079-123795079,hs11:125619040-125619040;hs3:123796304-123796304,hs3:159748233-159748233;hs3:123904517-123904517,hs3:154542810-154542810;hs3:123930144-123930144,hs3:144587159-144587159;hs3:124025603-124025603,hs11:101056464-101056464;hs3:124063113-124063113,hs3:179139985-179139985;hs3:124185143-124185143,hs11:61599499-61599499;hs3:124198734-124198734,hs3:143036473-143036473;hs3:124342685-124342685,hs11:85242424-85242424;hs3:124408457-124408457,hs11:57036464-57036464;hs3:124460012-124460012,hs11:95836242-95836242;hs3:124477777-124477777,hs3:158160521-158160521;hs3:124704274-124704274,hs11:4012723-4012723;hs3:124916025-124916025,hs3:166873636-166873636;hs3:124927223-124927223,hs11:46775416-46775416;hs3:124960858-124960858,hs11:77171575-77171575;hs3:124968166-124968166,hs11:62240407-62240407;hs3:125123837-125123837,hs11:83384540-83384540;hs3:125529708-125529708,hs3:173860733-173860733;hs3:125596169-125596169,hs11:47017806-47017806;hs3:125874352-125874352,hs3:192172068-192172068;hs3:125897657-125897657,hs3:129321450-129321450;hs3:125901426-125901426,hs11:93483648-93483648;hs3:125904432-125904432,hs11:116883360-116883360;hs3:125969994-125969994,hs3:165287317-165287317;hs3:126082256-126082256,hs3:169692558-169692558;hs3:126117801-126117801,hs3:155464363-155464363;hs3:126123591-126123591,hs3:127506213-127506213;hs3:126180396-126180396,hs11:41291116-41291116;hs3:126193369-126193369,hs3:127160048-127160048;hs3:126256485-126256485,hs11:76753385-76753385;hs3:126356723-126356723,hs3:127344153-127344153;hs3:126376120-126376120,hs3:134158444-134158444;hs3:126460989-126460989,hs3:183404578-183404578;hs3:126560735-126560735,hs11:129022708-129022708;hs3:126611559-126611559,hs3:155791440-155791440;hs3:126750821-126750821,hs3:146669587-146669587;hs3:126935839-126935839,hs11:90697433-90697433;hs3:127092488-127092488,hs3:169650756-169650756;hs3:127136163-127136163,hs11:6554205-6554205;hs3:127215945-127215945,hs11:103868448-103868448;hs3:127257075-127257075,hs11:60268242-60268242;hs3:127305963-127305963,hs11:60254588-60254588;hs3:127308136-127308136,hs11:47770623-47770623;hs3:127331807-127331807,hs11:27422175-27422175;hs3:127340822-127340822,hs11:14813882-14813882;hs3:127403654-127403654,hs3:137516082-137516082;hs3:127440103-127440103,hs11:125392752-125392752;hs3:127454866-127454866,hs11:24199453-24199453;hs3:127490072-127490072,hs11:109858483-109858483;hs3:127785629-127785629,hs3:188149444-188149444;hs3:127914299-127914299,hs3:184396952-184396952;hs3:128069886-128069886,hs11:67847542-67847542;hs3:128157222-128157222,hs11:69387219-69387219;hs3:128259936-128259936,hs11:80629469-80629469;hs3:128291384-128291384,hs11:116282665-116282665;hs3:128294061-128294061,hs11:16003215-16003215;hs3:128430833-128430833,hs11:117351586-117351586;hs3:128448043-128448043,hs11:101088162-101088162;hs3:128449145-128449145,hs11:12961908-12961908;hs3:128659138-128659138,hs11:27537295-27537295;hs3:128665092-128665092,hs11:19864259-19864259;hs3:128712195-128712195,hs11:84213000-84213000;hs3:128798019-128798019,hs3:189179684-189179684;hs3:128813170-128813170,hs11:116835763-116835763;hs3:128928414-128928414,hs11:64887906-64887906;hs3:128930376-128930376,hs11:41688541-41688541;hs3:129016056-129016056,hs3:133327814-133327814;hs3:129016057-129016057,hs3:133327815-133327815;hs3:129077608-129077608,hs11:60878415-60878415;hs3:129090160-129090160,hs11:92534765-92534765;hs3:129159051-129159051,hs3:166685564-166685564;hs3:129163073-129163073,hs3:133767911-133767911;hs3:129167314-129167314,hs11:83516698-83516698;hs3:129217748-129217748,hs11:115487734-115487734;hs3:129218250-129218250,hs11:34200170-34200170;hs3:129343322-129343322,hs11:56704496-56704496;hs3:130173424-130173424,hs11:133646954-133646954;hs3:130177157-130177157,hs11:47948495-47948495;hs3:130204967-130204967,hs11:4707046-4707046;hs3:130219103-130219103,hs3:185319555-185319555;hs3:130237966-130237966,hs11:105212676-105212676;hs3:130249661-130249661,hs3:195329973-195329973;hs3:130310593-130310593,hs11:21558432-21558432;hs3:130420263-130420263,hs3:196552985-196552985;hs3:130524913-130524913,hs3:167504118-167504118;hs3:130556125-130556125,hs3:181368494-181368494;hs3:130728525-130728525,hs11:48015049-48015049;hs3:131284328-131284328,hs11:47243481-47243481;hs3:131302039-131302039,hs11:65035539-65035539;hs3:131488534-131488534,hs3:146373973-146373973;hs3:131500212-131500212,hs11:65900211-65900211;hs3:131632393-131632393,hs3:146840518-146840518;hs3:131776621-131776621,hs3:187058829-187058829;hs3:132055613-132055613,hs11:124311276-124311276;hs3:132074704-132074704,hs3:183391188-183391188;hs3:132377795-132377795,hs3:136557508-136557508;hs3:132534927-132534927,hs11:34186312-34186312;hs3:132583845-132583845,hs3:134842304-134842304;hs3:132664431-132664431,hs3:150786832-150786832;hs3:132765585-132765585,hs3:185203257-185203257;hs3:133040665-133040665,hs11:15668260-15668260;hs3:133076890-133076890,hs11:116701465-116701465;hs3:133189241-133189241,hs11:112838599-112838599;hs3:133330807-133330807,hs11:132001384-132001384;hs3:133333020-133333020,hs3:177163373-177163373;hs3:133455850-133455850,hs11:72410072-72410072;hs3:133463237-133463237,hs11:97616628-97616628;hs3:133471261-133471261,hs3:171750047-171750047;hs3:133578861-133578861,hs11:975823-975823;hs3:133581045-133581045,hs11:12862555-12862555;hs3:133669135-133669135,hs11:9979545-9979545;hs3:133727089-133727089,hs3:195572683-195572683;hs3:134009833-134009833,hs3:179392766-179392766;hs3:134013037-134013037,hs11:106251620-106251620;hs3:134053414-134053414,hs11:70725263-70725263;hs3:134085483-134085483,hs11:81093470-81093470;hs3:134093114-134093114,hs11:74664120-74664120;hs3:134156707-134156707,hs3:177431273-177431273;hs3:134156707-134156707,hs3:177431273-177431273;hs3:134320772-134320772,hs11:98393315-98393315;hs3:134330383-134330383,hs11:129975136-129975136;hs3:134414923-134414923,hs11:110109517-110109517;hs3:134590830-134590830,hs11:102912652-102912652;hs3:134599930-134599930,hs11:126777700-126777700;hs3:134635538-134635538,hs11:19126554-19126554;hs3:134638647-134638647,hs3:189453346-189453346;hs3:134640660-134640660,hs11:22465640-22465640;hs3:134767745-134767745,hs11:6849447-6849447;hs3:134769511-134769511,hs11:35343200-35343200;hs3:134797436-134797436,hs11:77815605-77815605;hs3:134886505-134886505,hs11:14203339-14203339;hs3:135117960-135117960,hs3:145568748-145568748;hs3:135182236-135182236,hs3:158562469-158562469;hs3:135197815-135197815,hs3:179740192-179740192;hs3:135449623-135449623,hs11:82237398-82237398;hs3:135667469-135667469,hs11:88776072-88776072;hs3:135679503-135679503,hs3:149066356-149066356;hs3:136115945-136115945,hs3:176315097-176315097;hs3:136163819-136163819,hs11:34051103-34051103;hs3:136192894-136192894,hs11:66731760-66731760;hs3:136253827-136253827,hs3:184264582-184264582;hs3:136365925-136365925,hs3:163856518-163856518;hs3:136390693-136390693,hs3:146612209-146612209;hs3:136568392-136568392,hs3:160056674-160056674;hs3:136619212-136619212,hs3:173872777-173872777;hs3:136640078-136640078,hs11:46943878-46943878;hs3:136647024-136647024,hs11:3469108-3469108;hs3:136837527-136837527,hs11:59127276-59127276;hs3:137020105-137020105,hs11:118196723-118196723;hs3:137061430-137061430,hs11:82070810-82070810;hs3:137126977-137126977,hs11:16455107-16455107;hs3:137170188-137170188,hs11:5571455-5571455;hs3:137214640-137214640,hs11:88883037-88883037;hs3:137261942-137261942,hs11:11784861-11784861;hs3:137267674-137267674,hs3:148845769-148845769;hs3:137454906-137454906,hs11:61468333-61468333;hs3:137489852-137489852,hs3:197591268-197591268;hs3:137835223-137835223,hs3:165001324-165001324;hs3:137876902-137876902,hs3:154104588-154104588;hs3:137939779-137939779,hs11:129218819-129218819;hs3:138082369-138082369,hs11:67368470-67368470;hs3:138186842-138186842,hs11:44507421-44507421;hs3:138303705-138303705,hs11:104123881-104123881;hs3:138418721-138418721,hs11:32927900-32927900;hs3:138419087-138419087,hs11:93906718-93906718;hs3:138443248-138443248,hs3:175472268-175472268;hs3:138485973-138485973,hs11:68702965-68702965;hs3:138521861-138521861,hs11:34808718-34808718;hs3:138557095-138557095,hs11:94578227-94578227;hs3:138569200-138569200,hs11:77196885-77196885;hs3:138723454-138723454,hs11:74342903-74342903;hs3:138882386-138882386,hs11:74443234-74443234;hs3:139321749-139321749,hs3:180111306-180111306;hs3:139352724-139352724,hs11:62382140-62382140;hs3:139371581-139371581,hs11:4625930-4625930;hs3:139656854-139656854,hs11:126241727-126241727;hs3:139716065-139716065,hs3:152757421-152757421;hs3:139742888-139742888,hs11:62884272-62884272;hs3:139747974-139747974,hs11:45435210-45435210;hs3:139748416-139748416,hs11:129974844-129974844;hs3:140099050-140099050,hs11:79844204-79844204;hs3:140302711-140302711,hs3:151264747-151264747;hs3:140305112-140305112,hs3:141602135-141602135;hs3:140510341-140510341,hs11:81622994-81622994;hs3:140567533-140567533,hs11:121146118-121146118;hs3:140661009-140661009,hs3:146557671-146557671;hs3:140698635-140698635,hs3:179217825-179217825;hs3:141268415-141268415,hs11:624383-624383;hs3:141268415-141268415,hs11:624384-624384;hs3:141270330-141270330,hs11:36159203-36159203;hs3:141292574-141292574,hs11:66139896-66139896;hs3:141395028-141395028,hs11:74633259-74633259;hs3:141549752-141549752,hs11:29929448-29929448;hs3:141619763-141619763,hs11:117697604-117697604;hs3:141640671-141640671,hs3:166186701-166186701;hs3:141713697-141713697,hs3:181999890-181999890;hs3:141860633-141860633,hs3:170617296-170617296;hs3:142536454-142536454,hs11:90833470-90833470;hs3:142587374-142587374,hs11:55260268-55260268;hs3:142608382-142608382,hs11:127428009-127428009;hs3:142617428-142617428,hs3:156619600-156619600;hs3:142646644-142646644,hs3:157596290-157596290;hs3:142674795-142674795,hs11:65094523-65094523;hs3:142723475-142723475,hs3:157822011-157822011;hs3:142942320-142942320,hs11:87365079-87365079;hs3:143364975-143364975,hs3:191099239-191099239;hs3:143410167-143410167,hs11:16485507-16485507;hs3:143432049-143432049,hs3:144913969-144913969;hs3:143542915-143542915,hs11:1816465-1816465;hs3:143557899-143557899,hs11:5568334-5568334;hs3:143563139-143563139,hs11:36134716-36134716;hs3:143574507-143574507,hs11:114016684-114016684;hs3:143625610-143625610,hs11:80033738-80033738;hs3:143706757-143706757,hs11:128104658-128104658;hs3:143753990-143753990,hs11:106262231-106262231;hs3:144086820-144086820,hs11:86510457-86510457;hs3:144144338-144144338,hs11:116875481-116875481;hs3:144144339-144144339,hs11:116875482-116875482;hs3:144144339-144144339,hs11:116875482-116875482;hs3:144286990-144286990,hs3:145427715-145427715;hs3:144300213-144300213,hs3:191317658-191317658;hs3:144366583-144366583,hs3:144643741-144643741;hs3:144381598-144381598,hs11:19188770-19188770;hs3:144393049-144393049,hs11:32048672-32048672;hs3:144398262-144398262,hs11:71261250-71261250;hs3:144415856-144415856,hs11:127124509-127124509;hs3:144555823-144555823,hs11:59528540-59528540;hs3:144775894-144775894,hs11:10134001-10134001;hs3:144804068-144804068,hs11:44424631-44424631;hs3:144925099-144925099,hs11:4578780-4578780;hs3:145077027-145077027,hs11:45386366-45386366;hs3:145133179-145133179,hs11:96837152-96837152;hs3:145307672-145307672,hs3:163377106-163377106;hs3:145313273-145313273,hs3:145875993-145875993;hs3:145415978-145415978,hs11:105867735-105867735;hs3:145421806-145421806,hs11:21753935-21753935;hs3:145465940-145465940,hs11:102829143-102829143;hs3:145531813-145531813,hs11:48272363-48272363;hs3:145634062-145634062,hs11:4998131-4998131;hs3:145860410-145860410,hs3:146584526-146584526;hs3:146035639-146035639,hs11:29416532-29416532;hs3:146172042-146172042,hs3:189893838-189893838;hs3:146371061-146371061,hs11:78128469-78128469;hs3:146438827-146438827,hs11:34005283-34005283;hs3:146613716-146613716,hs11:65623285-65623285;hs3:146759287-146759287,hs11:30583721-30583721;hs3:146948059-146948059,hs3:194866968-194866968;hs3:146986791-146986791,hs11:60597034-60597034;hs3:147021987-147021987,hs11:108644272-108644272;hs3:147037428-147037428,hs11:5567914-5567914;hs3:147085207-147085207,hs11:113392509-113392509;hs3:147086384-147086384,hs3:172929350-172929350;hs3:147156599-147156599,hs11:11878427-11878427;hs3:147275521-147275521,hs11:33119531-33119531;hs3:147276312-147276312,hs11:29569603-29569603;hs3:147276312-147276312,hs11:29569602-29569602;hs3:147281847-147281847,hs11:81983429-81983429;hs3:147649078-147649078,hs11:3713523-3713523;hs3:148143312-148143312,hs11:105750482-105750482;hs3:148237838-148237838,hs11:87174912-87174912;hs3:148237838-148237838,hs11:87174913-87174913;hs3:148257328-148257328,hs11:58658049-58658049;hs3:148271632-148271632,hs11:40916845-40916845;hs3:148275675-148275675,hs3:157247346-157247346;hs3:148410086-148410086,hs11:46678208-46678208;hs3:148416833-148416833,hs11:118323448-118323448;hs3:148748240-148748240,hs11:74532976-74532976;hs3:148792777-148792777,hs11:101882860-101882860;hs3:148848916-148848916,hs11:107470720-107470720;hs3:148855204-148855204,hs11:89102455-89102455;hs3:149054949-149054949,hs11:42860666-42860666;hs3:149395537-149395537,hs11:59519083-59519083;hs3:149401024-149401024,hs3:171741955-171741955;hs3:149403937-149403937,hs11:84280186-84280186;hs3:149445071-149445071,hs11:893078-893078;hs3:149470920-149470920,hs3:194865821-194865821;hs3:149526235-149526235,hs11:88897559-88897559;hs3:149531648-149531648,hs11:87926314-87926314;hs3:149566656-149566656,hs11:65046959-65046959;hs3:149571033-149571033,hs11:129948172-129948172;hs3:149645323-149645323,hs11:113763182-113763182;hs3:149662132-149662132,hs11:8578360-8578360;hs3:149850604-149850604,hs11:76031212-76031212;hs3:149890556-149890556,hs11:16115771-16115771;hs3:149936168-149936168,hs11:18399698-18399698;hs3:150138743-150138743,hs11:39121608-39121608;hs3:150292721-150292721,hs11:25963482-25963482;hs3:150344868-150344868,hs11:37089146-37089146;hs3:150437646-150437646,hs11:110432600-110432600;hs3:150584250-150584250,hs3:171351035-171351035;hs3:150597235-150597235,hs11:59518114-59518114;hs3:150869625-150869625,hs11:101623307-101623307;hs3:150943598-150943598,hs11:5830905-5830905;hs3:150951384-150951384,hs3:191289000-191289000;hs3:151026064-151026064,hs3:181863072-181863072;hs3:151245658-151245658,hs11:3957367-3957367;hs3:151571851-151571851,hs11:70756170-70756170;hs3:151576026-151576026,hs11:74032251-74032251;hs3:151651582-151651582,hs11:77589894-77589894;hs3:151694061-151694061,hs11:96015059-96015059;hs3:151756063-151756063,hs11:64966246-64966246;hs3:151767149-151767149,hs11:90252472-90252472;hs3:151938298-151938298,hs3:187401375-187401375;hs3:151979447-151979447,hs3:160364379-160364379;hs3:152003876-152003876,hs11:33353346-33353346;hs3:152109025-152109025,hs11:63037145-63037145;hs3:152533907-152533907,hs3:155632158-155632158;hs3:152704853-152704853,hs3:185146280-185146280;hs3:152743267-152743267,hs3:182069908-182069908;hs3:152766027-152766027,hs11:96219348-96219348;hs3:152767634-152767634,hs11:73064703-73064703;hs3:152793667-152793667,hs11:11778885-11778885;hs3:152796843-152796843,hs11:24920665-24920665;hs3:152874073-152874073,hs11:46465409-46465409;hs3:152924572-152924572,hs11:26090623-26090623;hs3:153163945-153163945,hs11:86431317-86431317;hs3:153302498-153302498,hs11:60515095-60515095;hs3:153360452-153360452,hs3:173574947-173574947;hs3:153839998-153839998,hs11:12026577-12026577;hs3:153881083-153881083,hs11:93360253-93360253;hs3:153950390-153950390,hs11:68552325-68552325;hs3:153953625-153953625,hs11:125392598-125392598;hs3:154546156-154546156,hs3:165404295-165404295;hs3:154555721-154555721,hs11:128084118-128084118;hs3:154597362-154597362,hs11:39397908-39397908;hs3:154819789-154819789,hs11:84539223-84539223;hs3:155018116-155018116,hs3:159032763-159032763;hs3:155020000-155020000,hs11:110185444-110185444;hs3:155046679-155046679,hs11:115257803-115257803;hs3:155088229-155088229,hs11:87317628-87317628;hs3:155295980-155295980,hs11:130989657-130989657;hs3:155304871-155304871,hs11:65932080-65932080;hs3:155387960-155387960,hs11:61229993-61229993;hs3:155555362-155555362,hs11:83567710-83567710;hs3:155665075-155665075,hs3:168772176-168772176;hs3:155693706-155693706,hs11:99983540-99983540;hs3:155818918-155818918,hs11:122600230-122600230;hs3:155820861-155820861,hs11:19486253-19486253;hs3:156743161-156743161,hs11:7462646-7462646;hs3:156809709-156809709,hs11:61914457-61914457;hs3:156867833-156867833,hs11:56251198-56251198;hs3:157221540-157221540,hs11:50484434-50484434;hs3:157412377-157412377,hs3:189591943-189591943;hs3:157522274-157522274,hs11:97049106-97049106;hs3:157525897-157525897,hs11:65825379-65825379;hs3:157549592-157549592,hs3:185965987-185965987;hs3:157610963-157610963,hs11:11405371-11405371;hs3:157898769-157898769,hs3:160795242-160795242;hs3:157914685-157914685,hs11:46966368-46966368;hs3:157996775-157996775,hs11:21378277-21378277;hs3:158289637-158289637,hs11:72431706-72431706;hs3:158479021-158479021,hs11:104093627-104093627;hs3:158592765-158592765,hs11:63611636-63611636;hs3:158761407-158761407,hs11:46901783-46901783;hs3:158863834-158863834,hs11:92276765-92276765;hs3:158874806-158874806,hs11:35635390-35635390;hs3:158890853-158890853,hs11:30522781-30522781;hs3:158981386-158981386,hs11:78143465-78143465;hs3:158982311-158982311,hs11:110276930-110276930;hs3:159805847-159805847,hs3:196156659-196156659;hs3:159832733-159832733,hs3:184997824-184997824;hs3:159848878-159848878,hs11:50000968-50000968;hs3:159948361-159948361,hs3:171215323-171215323;hs3:159963079-159963079,hs11:13473282-13473282;hs3:159968146-159968146,hs11:114168398-114168398;hs3:159968994-159968994,hs11:74441796-74441796;hs3:159968994-159968994,hs11:74441797-74441797;hs3:159969521-159969521,hs3:185403871-185403871;hs3:159970070-159970070,hs3:179747037-179747037;hs3:159982518-159982518,hs3:180007325-180007325;hs3:160234366-160234366,hs11:58413948-58413948;hs3:160329608-160329608,hs11:25701190-25701190;hs3:160556023-160556023,hs3:191789433-191789433;hs3:160613031-160613031,hs3:194561108-194561108;hs3:160807881-160807881,hs11:111169343-111169343;hs3:160878774-160878774,hs11:37708410-37708410;hs3:160893479-160893479,hs11:67556557-67556557;hs3:160943008-160943008,hs11:113735130-113735130;hs3:161907467-161907467,hs3:180650056-180650056;hs3:161960844-161960844,hs11:12735557-12735557;hs3:161965769-161965769,hs11:87813981-87813981;hs3:162012170-162012170,hs11:111276927-111276927;hs3:162084952-162084952,hs11:45908532-45908532;hs3:162143709-162143709,hs11:65963902-65963902;hs3:162304648-162304648,hs3:188481138-188481138;hs3:162331381-162331381,hs3:175111042-175111042;hs3:162366895-162366895,hs11:4603232-4603232;hs3:162473501-162473501,hs11:73676720-73676720;hs3:162707561-162707561,hs11:111354784-111354784;hs3:162892385-162892385,hs11:117743522-117743522;hs3:162954942-162954942,hs11:104206825-104206825;hs3:162989980-162989980,hs3:193311121-193311121;hs3:163195348-163195348,hs11:49100023-49100023;hs3:163220820-163220820,hs3:183098213-183098213;hs3:163383715-163383715,hs11:117463914-117463914;hs3:163415243-163415243,hs3:186994701-186994701;hs3:163680982-163680982,hs11:39647332-39647332;hs3:163859354-163859354,hs11:43999508-43999508;hs3:164358533-164358533,hs11:22088490-22088490;hs3:164491246-164491246,hs3:171530479-171530479;hs3:164513521-164513521,hs3:167960999-167960999;hs3:164536674-164536674,hs11:5073526-5073526;hs3:164541321-164541321,hs11:1242912-1242912;hs3:164541321-164541321,hs11:1242913-1242913;hs3:164617266-164617266,hs3:187273493-187273493;hs3:164624224-164624224,hs11:4327583-4327583;hs3:164812569-164812569,hs3:182058343-182058343;hs3:164860547-164860547,hs11:82553796-82553796;hs3:164978011-164978011,hs11:60883296-60883296;hs3:165043262-165043262,hs11:108375657-108375657;hs3:165461991-165461991,hs3:189707361-189707361;hs3:165480395-165480395,hs11:49202082-49202082;hs3:165550651-165550651,hs3:187938444-187938444;hs3:165574211-165574211,hs11:111159086-111159086;hs3:165601199-165601199,hs11:42366696-42366696;hs3:165660338-165660338,hs11:107647331-107647331;hs3:165664191-165664191,hs3:169873620-169873620;hs3:165865706-165865706,hs11:6629330-6629330;hs3:165868683-165868683,hs11:14979027-14979027;hs3:166195357-166195357,hs11:104226066-104226066;hs3:166565048-166565048,hs11:49010496-49010496;hs3:166687873-166687873,hs11:23583357-23583357;hs3:166693491-166693491,hs11:11788127-11788127;hs3:166706439-166706439,hs11:22722436-22722436;hs3:166803758-166803758,hs3:195251243-195251243;hs3:166833990-166833990,hs11:62185977-62185977;hs3:166877927-166877927,hs11:109074170-109074170;hs3:167038302-167038302,hs11:96157498-96157498;hs3:167624407-167624407,hs11:109543293-109543293;hs3:167954717-167954717,hs11:132115064-132115064;hs3:167978371-167978371,hs11:134190179-134190179;hs3:168014941-168014941,hs11:30619091-30619091;hs3:168317700-168317700,hs3:170892261-170892261;hs3:168354905-168354905,hs11:129822116-129822116;hs3:168679456-168679456,hs11:110262070-110262070;hs3:168780268-168780268,hs11:99519051-99519051;hs3:168783608-168783608,hs11:78314429-78314429;hs3:168930114-168930114,hs3:184412983-184412983;hs3:169489588-169489588,hs11:50401023-50401023;hs3:169522282-169522282,hs3:180844896-180844896;hs3:169525745-169525745,hs11:29016037-29016037;hs3:169527157-169527157,hs11:78244581-78244581;hs3:169626918-169626918,hs11:134532172-134532172;hs3:169654664-169654664,hs11:116465767-116465767;hs3:169768356-169768356,hs3:182362622-182362622;hs3:169770291-169770291,hs11:77200637-77200637;hs3:169775310-169775310,hs11:60371973-60371973;hs3:169882988-169882988,hs11:63873164-63873164;hs3:169941276-169941276,hs11:6339503-6339503;hs3:170243150-170243150,hs11:13225709-13225709;hs3:170252889-170252889,hs11:80139463-80139463;hs3:170608430-170608430,hs11:18423526-18423526;hs3:170838758-170838758,hs3:182293590-182293590;hs3:170864631-170864631,hs3:173002289-173002289;hs3:170876882-170876882,hs11:36220178-36220178;hs3:171041786-171041786,hs11:117360215-117360215;hs3:171123689-171123689,hs11:106156755-106156755;hs3:171163404-171163404,hs11:13218039-13218039;hs3:171216421-171216421,hs11:127185074-127185074;hs3:171395935-171395935,hs11:47578221-47578221;hs3:171492029-171492029,hs11:81268750-81268750;hs3:171738225-171738225,hs11:14353992-14353992;hs3:171754872-171754872,hs11:75027316-75027316;hs3:171818331-171818331,hs11:82501307-82501307;hs3:172348106-172348106,hs11:129547721-129547721;hs3:172364572-172364572,hs11:44575316-44575316;hs3:172407349-172407349,hs11:63222266-63222266;hs3:172432793-172432793,hs11:132720998-132720998;hs3:172484946-172484946,hs11:76159459-76159459;hs3:172484946-172484946,hs11:76159460-76159460;hs3:172664217-172664217,hs11:13183854-13183854;hs3:172676969-172676969,hs11:84093318-84093318;hs3:172893619-172893619,hs3:196934117-196934117;hs3:173002855-173002855,hs11:65123095-65123095;hs3:173184543-173184543,hs11:41402266-41402266;hs3:173457520-173457520,hs11:101621172-101621172;hs3:173613917-173613917,hs3:184738513-184738513;hs3:173840462-173840462,hs11:64601956-64601956;hs3:173842387-173842387,hs11:43731519-43731519;hs3:173859202-173859202,hs11:98010347-98010347;hs3:173930835-173930835,hs11:98074699-98074699;hs3:173994397-173994397,hs11:7485035-7485035;hs3:174013131-174013131,hs11:56685225-56685225;hs3:174230640-174230640,hs11:132718231-132718231;hs3:174398300-174398300,hs11:106957045-106957045;hs3:174975877-174975877,hs11:44149041-44149041;hs3:175000683-175000683,hs3:176683539-176683539;hs3:175035357-175035357,hs11:42814888-42814888;hs3:175102990-175102990,hs11:7021605-7021605;hs3:175189100-175189100,hs11:15645475-15645475;hs3:175221507-175221507,hs11:128127974-128127974;hs3:175337140-175337140,hs11:134489176-134489176;hs3:175603514-175603514,hs11:133907243-133907243;hs3:175693440-175693440,hs3:184924408-184924408;hs3:175822251-175822251,hs11:125718599-125718599;hs3:175859734-175859734,hs11:77729555-77729555;hs3:176269698-176269698,hs11:23951133-23951133;hs3:176274265-176274265,hs11:92338405-92338405;hs3:176303854-176303854,hs11:69798297-69798297;hs3:176448840-176448840,hs11:55827704-55827704;hs3:176774049-176774049,hs11:80539608-80539608;hs3:176872739-176872739,hs11:11395347-11395347;hs3:176922403-176922403,hs11:105218202-105218202;hs3:176967148-176967148,hs11:58024171-58024171;hs3:177017668-177017668,hs11:130758556-130758556;hs3:177174779-177174779,hs11:48667045-48667045;hs3:177430807-177430807,hs11:57389481-57389481;hs3:177444330-177444330,hs11:8726156-8726156;hs3:177665965-177665965,hs11:6286773-6286773;hs3:177740515-177740515,hs3:182528817-182528817;hs3:177742155-177742155,hs11:56619166-56619166;hs3:177794273-177794273,hs11:17373392-17373392;hs3:178153308-178153308,hs11:30150934-30150934;hs3:178180483-178180483,hs11:114816169-114816169;hs3:178207445-178207445,hs11:19420365-19420365;hs3:178301526-178301526,hs11:122924158-122924158;hs3:178369486-178369486,hs11:68672394-68672394;hs3:178401020-178401020,hs11:113300344-113300344;hs3:178457474-178457474,hs11:68956669-68956669;hs3:178461579-178461579,hs11:45407508-45407508;hs3:178536761-178536761,hs11:93594182-93594182;hs3:178758777-178758777,hs11:24918183-24918183;hs3:178896856-178896856,hs11:93471452-93471452;hs3:179147418-179147418,hs3:186993703-186993703;hs3:179196231-179196231,hs11:7166456-7166456;hs3:179303411-179303411,hs3:187227170-187227170;hs3:179444608-179444608,hs11:838919-838919;hs3:179705574-179705574,hs11:95730208-95730208;hs3:179967933-179967933,hs11:38104749-38104749;hs3:179989667-179989667,hs11:87405243-87405243;hs3:180002426-180002426,hs11:98585711-98585711;hs3:180410958-180410958,hs11:38936200-38936200;hs3:180719095-180719095,hs11:35884436-35884436;hs3:180733281-180733281,hs11:112732204-112732204;hs3:180753030-180753030,hs11:58656286-58656286;hs3:180773708-180773708,hs11:134826709-134826709;hs3:181093859-181093859,hs11:45266801-45266801;hs3:181096910-181096910,hs11:130381655-130381655;hs3:181170851-181170851,hs11:103059277-103059277;hs3:181299454-181299454,hs11:15417216-15417216;hs3:181396499-181396499,hs3:185668317-185668317;hs3:181428942-181428942,hs11:33804538-33804538;hs3:181452187-181452187,hs11:130031685-130031685;hs3:181505388-181505388,hs11:108852514-108852514;hs3:181738436-181738436,hs11:63033030-63033030;hs3:181944879-181944879,hs11:45436465-45436465;hs3:182132465-182132465,hs11:3486005-3486005;hs3:182139589-182139589,hs3:195919485-195919485;hs3:182191652-182191652,hs11:8580073-8580073;hs3:182296506-182296506,hs11:11822136-11822136;hs3:182312282-182312282,hs11:94934158-94934158;hs3:182537374-182537374,hs11:85391175-85391175;hs3:182641832-182641832,hs11:9944919-9944919;hs3:182673245-182673245,hs11:4699194-4699194;hs3:182719103-182719103,hs11:1279506-1279506;hs3:182828326-182828326,hs11:97747490-97747490;hs3:182910354-182910354,hs11:74363670-74363670;hs3:182941694-182941694,hs11:113071849-113071849;hs3:182966480-182966480,hs3:193281001-193281001;hs3:182972280-182972280,hs11:3165094-3165094;hs3:182994962-182994962,hs11:41186524-41186524;hs3:183102288-183102288,hs3:195174096-195174096;hs3:183177013-183177013,hs11:30415627-30415627;hs3:183185680-183185680,hs11:34585755-34585755;hs3:183216408-183216408,hs11:132359162-132359162;hs3:183402742-183402742,hs11:73035521-73035521;hs3:183446885-183446885,hs11:51293203-51293203;hs3:183481592-183481592,hs11:108334861-108334861;hs3:183786467-183786467,hs11:6390541-6390541;hs3:183789269-183789269,hs11:92071791-92071791;hs3:183914911-183914911,hs11:72670947-72670947;hs3:183957027-183957027,hs11:126775058-126775058;hs3:184030808-184030808,hs11:118290231-118290231;hs3:184032885-184032885,hs11:546056-546056;hs3:184054042-184054042,hs11:59447989-59447989;hs3:184127543-184127543,hs11:35339008-35339008;hs3:184129432-184129432,hs3:191441548-191441548;hs3:184226667-184226667,hs11:63645515-63645515;hs3:184330708-184330708,hs11:30061359-30061359;hs3:184518260-184518260,hs11:84199231-84199231;hs3:184532850-184532850,hs3:187216353-187216353;hs3:184596443-184596443,hs11:83665575-83665575;hs3:184616386-184616386,hs11:49435470-49435470;hs3:184667063-184667063,hs11:99367843-99367843;hs3:184670147-184670147,hs11:74390094-74390094;hs3:184702011-184702011,hs11:113418352-113418352;hs3:184725944-184725944,hs11:32056652-32056652;hs3:184744529-184744529,hs11:42218163-42218163;hs3:185023523-185023523,hs11:121065942-121065942;hs3:185085576-185085576,hs11:118358188-118358188;hs3:185089774-185089774,hs11:44944760-44944760;hs3:185095045-185095045,hs11:101842048-101842048;hs3:185395562-185395562,hs11:75094006-75094006;hs3:185441065-185441065,hs11:973875-973875;hs3:185476253-185476253,hs11:39666875-39666875;hs3:185504114-185504114,hs11:1287050-1287050;hs3:185672075-185672075,hs11:70188788-70188788;hs3:185699145-185699145,hs6:137372095-137372095;hs3:185707222-185707222,hs3:185743100-185743100;hs3:185715476-185715476,hs6:137351172-137351172;hs3:185717015-185717015,hs6:137368834-137368834;hs3:185738651-185738651,hs6:146580725-146580725;hs3:185740890-185740890,hs11:87538776-87538776;hs3:185745180-185745180,hs11:85830423-85830423;hs3:185754016-185754016,hs6:152036373-152036373;hs3:185789593-185789593,hs11:12864620-12864620;hs3:185795659-185795659,hs11:125772637-125772637;hs3:185823012-185823012,hs11:70954909-70954909;hs3:185840014-185840014,hs3:190066109-190066109;hs3:185915324-185915324,hs11:44299817-44299817;hs3:186004404-186004404,hs11:60692029-60692029;hs3:186075847-186075847,hs11:90827111-90827111;hs3:186191178-186191178,hs11:134211191-134211191;hs3:186766649-186766649,hs6:146586564-146586564;hs3:186766692-186766692,hs6:137352027-137352027;hs3:186851116-186851116,hs11:59314170-59314170;hs3:187234955-187234955,hs11:25815840-25815840;hs3:187588397-187588397,hs3:189825423-189825423;hs3:187604204-187604204,hs11:10476687-10476687;hs3:187760758-187760758,hs11:104114125-104114125;hs3:188160253-188160253,hs11:64221497-64221497;hs3:188209596-188209596,hs11:11348464-11348464;hs3:188250487-188250487,hs11:27394274-27394274;hs3:188794722-188794722,hs11:23979038-23979038;hs3:189076509-189076509,hs11:119585315-119585315;hs3:189133538-189133538,hs11:125441370-125441370;hs3:189149204-189149204,hs11:876506-876506;hs3:189197054-189197054,hs11:130738472-130738472;hs3:189214503-189214503,hs11:129482030-129482030;hs3:189444690-189444690,hs11:3191885-3191885;hs3:189456312-189456312,hs11:88531126-88531126;hs3:190701568-190701568,hs11:109918344-109918344;hs3:190800230-190800230,hs11:105911250-105911250;hs3:191437294-191437294,hs11:45885133-45885133;hs3:191450847-191450847,hs11:119031672-119031672;hs3:191529430-191529430,hs11:45209156-45209156;hs3:191634478-191634478,hs11:128130317-128130317;hs3:191765643-191765643,hs11:22639175-22639175;hs3:191849875-191849875,hs11:24924204-24924204;hs3:192048318-192048318,hs11:124171987-124171987;hs3:192058782-192058782,hs11:114963746-114963746;hs3:192129584-192129584,hs11:17707020-17707020;hs3:192344553-192344553,hs11:125641376-125641376;hs3:192558767-192558767,hs11:109685228-109685228;hs3:192558768-192558768,hs11:109685229-109685229;hs3:192872501-192872501,hs11:34780655-34780655;hs3:193265842-193265842,hs11:92498076-92498076;hs3:193266178-193266178,hs11:3862327-3862327;hs3:193358919-193358919,hs11:85178397-85178397;hs3:193709875-193709875,hs11:124891210-124891210;hs3:193929193-193929193,hs3:196790453-196790453;hs3:194434970-194434970,hs11:82686942-82686942;hs3:194448014-194448014,hs11:34223711-34223711;hs3:194486191-194486191,hs11:112455338-112455338;hs3:194799790-194799790,hs11:3844433-3844433;hs3:194802112-194802112,hs11:1242637-1242637;hs3:194922128-194922128,hs11:12871084-12871084;hs3:195282122-195282122,hs11:29281978-29281978;hs3:195569849-195569849,hs11:84429833-84429833;hs3:195640009-195640009,hs11:83624877-83624877;hs3:195649955-195649955,hs11:87263234-87263234;hs3:195760826-195760826,hs11:124015693-124015693;hs3:195804120-195804120,hs11:6492243-6492243;hs3:195908856-195908856,hs11:49399939-49399939;hs3:195918795-195918795,hs11:96005765-96005765;hs3:196010490-196010490,hs11:130004009-130004009;hs3:196072961-196072961,hs11:82801084-82801084;hs3:196092529-196092529,hs11:48366713-48366713;hs3:196127077-196127077,hs11:7194204-7194204;hs3:196264049-196264049,hs11:50229578-50229578;hs3:196284945-196284945,hs11:30597946-30597946;hs3:196293424-196293424,hs11:87925464-87925464;hs3:196301548-196301548,hs11:94410108-94410108;hs3:196529406-196529406,hs11:31536263-31536263;hs3:196703884-196703884,hs11:34782793-34782793;hs3:196763776-196763776,hs11:48114170-48114170;hs3:196765171-196765171,hs11:68158492-68158492;hs3:196765422-196765422,hs11:63854974-63854974;hs3:196830409-196830409,hs11:6722431-6722431;hs3:196830409-196830409,hs6:47255248-47255248;hs3:196957833-196957833,hs11:129729639-129729639;hs3:197240149-197240149,hs11:105237369-105237369;hs3:197248745-197248745,hs11:41329520-41329520;hs3:197273710-197273710,hs11:104970196-104970196;hs3:197282177-197282177,hs11:57194651-57194651;hs3:197282257-197282257,hs11:45611158-45611158;hs3:197676687-197676687,hs11:126837507-126837507;hs3:197681809-197681809,hs11:70747528-70747528;hs3:197852206-197852206,hs11:13158702-13158702;hs4:94968311-94968311,hs11:24918184-24918184;hs4:185977800-185977800,hs17:43211206-43211206;hs5:103829928-103829928,hs17:9840872-9840872;hs5:141494777-141494777,hs5:141500310-141500310;hs5:164737132-164737132,hs5:165108670-165108670;hs6:114563773-114563773,hs22:47334955-47334955;hs6:129319533-129319533,hsX:123921244-123921244;hs6:137316802-137316802,hs6:144734899-144734899;hs6:137348159-137348159,hs6:146599094-146599094;hs6:137349897-137349897,hs6:152037909-152037909;hs6:137352242-137352242,hs6:152037947-152037947;hs6:137353741-137353741,hs6:152038389-152038389;hs6:137354485-137354485,hs6:137381520-137381520;hs6:137354452-137354452,hs6:137369981-137369981;hs6:137367063-137367063,hs6:152038390-152038390;hs6:137372944-137372944,hs6:144706513-144706513;hs6:144705836-144705836,hs6:152054061-152054061;hs7:100907088-100907088,hs8:105882518-105882518;hs7:130261755-130261755,hs12:60677830-60677830;hs11:231868-231868,hs11:117444254-117444254;hs11:383715-383715,hs11:88281967-88281967;hs11:408780-408780,hs11:74884510-74884510;hs11:451688-451688,hs11:67901432-67901432;hs11:478877-478877,hs11:86141526-86141526;hs11:493359-493359,hs11:129940379-129940379;hs11:512739-512739,hs11:64967796-64967796;hs11:606261-606261,hs11:109121484-109121484;hs11:658765-658765,hs11:119572295-119572295;hs11:777269-777269,hs11:130769037-130769037;hs11:787786-787786,hs11:65261521-65261521;hs11:795527-795527,hs11:65163658-65163658;hs11:839426-839426,hs11:127284589-127284589;hs11:841844-841844,hs11:65624652-65624652;hs11:865484-865484,hs11:117062500-117062500;hs11:945911-945911,hs11:62665956-62665956;hs11:1369560-1369560,hs11:107648967-107648967;hs11:1375340-1375340,hs11:109684475-109684475;hs11:1434750-1434750,hs11:79347649-79347649;hs11:1553593-1553593,hs11:96264106-96264106;hs11:1579714-1579714,hs11:44591695-44591695;hs11:2635841-2635841,hs11:119578083-119578083;hs11:2638620-2638620,hs11:78338348-78338348;hs11:2772388-2772388,hs11:69384903-69384903;hs11:3030549-3030549,hs11:17385353-17385353;hs11:3086078-3086078,hs11:55185122-55185122;hs11:3100932-3100932,hs11:81660855-81660855;hs11:3110679-3110679,hs11:116386480-116386480;hs11:3484312-3484312,hs11:30734937-30734937;hs11:3546478-3546478,hs11:86369729-86369729;hs11:3708066-3708066,hs11:58861127-58861127;hs11:3808866-3808866,hs11:36770707-36770707;hs11:3925418-3925418,hs11:55537293-55537293;hs11:3938395-3938395,hs11:109790335-109790335;hs11:3954752-3954752,hs11:83451774-83451774;hs11:4185740-4185740,hs11:46130005-46130005;hs11:4603430-4603430,hs11:41316479-41316479;hs11:4665725-4665725,hs11:60929995-60929995;hs11:4673837-4673837,hs11:99357662-99357662;hs11:4823558-4823558,hs11:89106803-89106803;hs11:4943228-4943228,hs11:26641832-26641832;hs11:4946876-4946876,hs11:61928049-61928049;hs11:5004786-5004786,hs11:99646781-99646781;hs11:5022328-5022328,hs11:42715762-42715762;hs11:5068079-5068079,hs11:42291092-42291092;hs11:5412389-5412389,hs11:56076957-56076957;hs11:5599891-5599891,hs11:21978911-21978911;hs11:5635311-5635311,hs11:81823938-81823938;hs11:5673502-5673502,hs11:8322999-8322999;hs11:5810812-5810812,hs11:130711082-130711082;hs11:5841813-5841813,hs11:70784377-70784377;hs11:5888385-5888385,hs11:79957115-79957115;hs11:6366429-6366429,hs11:34069598-34069598;hs11:6387996-6387996,hs11:112879805-112879805;hs11:6400641-6400641,hs11:58068682-58068682;hs11:6410589-6410589,hs11:46072243-46072243;hs11:6533364-6533364,hs11:65314131-65314131;hs11:6671751-6671751,hs11:35137974-35137974;hs11:7153539-7153539,hs11:78261431-78261431;hs11:7161924-7161924,hs11:125526212-125526212;hs11:7175642-7175642,hs11:28299050-28299050;hs11:7442826-7442826,hs11:67356308-67356308;hs11:8124867-8124867,hs11:21066677-21066677;hs11:8164638-8164638,hs11:26795644-26795644;hs11:8174755-8174755,hs11:132379726-132379726;hs11:8601264-8601264,hs11:118808369-118808369;hs11:9009115-9009115,hs11:48207363-48207363;hs11:9223677-9223677,hs11:91403775-91403775;hs11:9264565-9264565,hs11:98711605-98711605;hs11:9378317-9378317,hs11:132270871-132270871;hs11:9544086-9544086,hs11:67144679-67144679;hs11:9625641-9625641,hs11:87935970-87935970;hs11:9922392-9922392,hs11:46898275-46898275;hs11:9985284-9985284,hs11:19735503-19735503;hs11:10074446-10074446,hs11:57384977-57384977;hs11:11063100-11063100,hs11:74584228-74584228;hs11:11111604-11111604,hs11:80194876-80194876;hs11:11165131-11165131,hs11:112386749-112386749;hs11:11299625-11299625,hs11:68538695-68538695;hs11:11343490-11343490,hs11:32768873-32768873;hs11:11389624-11389624,hs11:97761001-97761001;hs11:11392762-11392762,hs11:108369850-108369850;hs11:11399929-11399929,hs11:101196468-101196468;hs11:11416418-11416418,hs11:86670011-86670011;hs11:11491283-11491283,hs11:90877536-90877536;hs11:11615414-11615414,hs11:43945590-43945590;hs11:11642145-11642145,hs11:96982289-96982289;hs11:11899227-11899227,hs11:13639718-13639718;hs11:11985903-11985903,hs11:113408608-113408608;hs11:12528506-12528506,hs11:13463932-13463932;hs11:12650846-12650846,hs11:51389605-51389605;hs11:12667341-12667341,hs11:33153972-33153972;hs11:12826386-12826386,hs11:106434811-106434811;hs11:12859970-12859970,hs11:96965690-96965690;hs11:12952300-12952300,hs11:48099412-48099412;hs11:13170034-13170034,hs11:51426005-51426005;hs11:13218287-13218287,hs11:28293131-28293131;hs11:13316905-13316905,hs11:19446503-19446503;hs11:13331939-13331939,hs11:33068744-33068744;hs11:13392248-13392248,hs11:116875038-116875038;hs11:13398470-13398470,hs11:71792210-71792210;hs11:13508319-13508319,hs11:15586984-15586984;hs11:13527017-13527017,hs11:62375433-62375433;hs11:13531536-13531536,hs11:95838205-95838205;hs11:14134691-14134691,hs11:32601143-32601143;hs11:14430454-14430454,hs11:62773318-62773318;hs11:14468173-14468173,hs11:63684610-63684610;hs11:15001484-15001484,hs11:113759538-113759538;hs11:15166838-15166838,hs11:64370403-64370403;hs11:15276898-15276898,hs11:113534017-113534017;hs11:15665976-15665976,hs11:48136408-48136408;hs11:15993009-15993009,hs11:96635668-96635668;hs11:16032432-16032432,hs11:50394547-50394547;hs11:16345614-16345614,hs11:16346490-16346490;hs11:16528514-16528514,hs11:88608398-88608398;hs11:16532793-16532793,hs11:66362522-66362522;hs11:16721894-16721894,hs11:113012149-113012149;hs11:16819287-16819287,hs11:109566143-109566143;hs11:16836808-16836808,hs11:118491502-118491502;hs11:17202013-17202013,hs11:29738947-29738947;hs11:17308236-17308236,hs11:104141103-104141103;hs11:17364895-17364895,hs11:75828381-75828381;hs11:17534556-17534556,hs11:41176065-41176065;hs11:18009740-18009740,hs11:55838493-55838493;hs11:18107611-18107611,hs11:96927797-96927797;hs11:18289908-18289908,hs11:29857230-29857230;hs11:18298590-18298590,hs11:97338552-97338552;hs11:18421856-18421856,hs11:129951522-129951522;hs11:18423808-18423808,hs11:128824138-128824138;hs11:18452048-18452048,hs11:110734678-110734678;hs11:18610245-18610245,hs11:47069803-47069803;hs11:18618936-18618936,hs11:117417300-117417300;hs11:19087098-19087098,hs11:69790562-69790562;hs11:19182778-19182778,hs11:126299455-126299455;hs11:19206034-19206034,hs11:62336688-62336688;hs11:19522110-19522110,hs11:43508280-43508280;hs11:19589030-19589030,hs11:109064258-109064258;hs11:19637054-19637054,hs11:33139617-33139617;hs11:20055807-20055807,hs11:22048722-22048722;hs11:20072074-20072074,hs11:98075979-98075979;hs11:20505317-20505317,hs11:131593699-131593699;hs11:20990198-20990198,hs11:108060700-108060700;hs11:21086188-21086188,hs11:71035774-71035774;hs11:21134606-21134606,hs11:74247663-74247663;hs11:21188957-21188957,hs11:110731941-110731941;hs11:21398719-21398719,hs11:45352349-45352349;hs11:21461767-21461767,hs11:103797944-103797944;hs11:21712222-21712222,hs11:45434096-45434096;hs11:21718201-21718201,hs11:107096863-107096863;hs11:21920680-21920680,hs11:81489806-81489806;hs11:21938727-21938727,hs11:128230528-128230528;hs11:22002249-22002249,hs11:92883239-92883239;hs11:22057828-22057828,hs11:84365475-84365475;hs11:22496828-22496828,hs11:64556839-64556839;hs11:22551686-22551686,hs11:88483495-88483495;hs11:22759278-22759278,hs11:134290574-134290574;hs11:22830583-22830583,hs11:126111775-126111775;hs11:22969560-22969560,hs11:128541988-128541988;hs11:23458739-23458739,hs11:65957755-65957755;hs11:23671148-23671148,hs11:103128217-103128217;hs11:23980723-23980723,hs11:94250376-94250376;hs11:24121060-24121060,hs11:116404147-116404147;hs11:24135120-24135120,hs11:46820160-46820160;hs11:24437670-24437670,hs11:93400142-93400142;hs11:24927478-24927478,hs11:118271177-118271177;hs11:25212073-25212073,hs11:74360741-74360741;hs11:25260993-25260993,hs11:26017189-26017189;hs11:25293464-25293464,hs11:91218819-91218819;hs11:25818468-25818468,hs11:49120152-49120152;hs11:25948933-25948933,hs11:85878562-85878562;hs11:26091565-26091565,hs11:60350106-60350106;hs11:26551470-26551470,hs11:48701243-48701243;hs11:27006944-27006944,hs11:63878565-63878565;hs11:27018129-27018129,hs11:107877901-107877901;hs11:27285502-27285502,hs11:27286619-27286619;hs11:27286359-27286359,hs11:69038612-69038612;hs11:27633668-27633668,hs11:104810238-104810238;hs11:27668439-27668439,hs11:68820226-68820226;hs11:27721468-27721468,hs11:69067400-69067400;hs11:27762071-27762071,hs11:130994579-130994579;hs11:28374492-28374492,hs11:117353743-117353743;hs11:28423026-28423026,hs11:55773130-55773130;hs11:28841695-28841695,hs11:64027913-64027913;hs11:28935934-28935934,hs11:34817889-34817889;hs11:28956669-28956669,hs11:36409805-36409805;hs11:29348364-29348364,hs11:73973227-73973227;hs11:29603391-29603391,hs11:134475697-134475697;hs11:29731037-29731037,hs11:48541964-48541964;hs11:30219316-30219316,hs11:35337422-35337422;hs11:30312987-30312987,hs11:109411642-109411642;hs11:30344564-30344564,hs11:56554942-56554942;hs11:30590646-30590646,hs11:30591260-30591260;hs11:30591266-30591266,hs11:67894675-67894675;hs11:30879527-30879527,hs11:115819811-115819811;hs11:31468815-31468815,hs11:66199286-66199286;hs11:31632471-31632471,hs11:34369085-34369085;hs11:31633556-31633556,hs11:45388366-45388366;hs11:31634190-31634190,hs11:45611884-45611884;hs11:31884686-31884686,hs11:129403298-129403298;hs11:32859725-32859725,hs11:64883126-64883126;hs11:33442795-33442795,hs11:74333828-74333828;hs11:33462839-33462839,hs11:73851942-73851942;hs11:33488147-33488147,hs11:62591446-62591446;hs11:33878205-33878205,hs11:42095797-42095797;hs11:33983607-33983607,hs11:56709069-56709069;hs11:33986866-33986866,hs11:81118270-81118270;hs11:34060906-34060906,hs11:78302648-78302648;hs11:34105335-34105335,hs11:61606368-61606368;hs11:34199618-34199618,hs11:100070855-100070855;hs11:34224846-34224846,hs11:68827650-68827650;hs11:34616434-34616434,hs11:60630793-60630793;hs11:34806969-34806969,hs11:119534600-119534600;hs11:34963435-34963435,hs11:125046727-125046727;hs11:35010543-35010543,hs11:67557722-67557722;hs11:35112430-35112430,hs11:37138557-37138557;hs11:35115597-35115597,hs11:79412916-79412916;hs11:35124259-35124259,hs11:118984284-118984284;hs11:35257073-35257073,hs11:40355436-40355436;hs11:35299216-35299216,hs11:120591608-120591608;hs11:35578110-35578110,hs11:117345590-117345590;hs11:35682467-35682467,hs11:46627476-46627476;hs11:35684731-35684731,hs11:110148117-110148117;hs11:35739295-35739295,hs11:116070027-116070027;hs11:35744373-35744373,hs11:44888414-44888414;hs11:35852915-35852915,hs11:113964860-113964860;hs11:35869519-35869519,hs11:45908750-45908750;hs11:35876139-35876139,hs11:67891350-67891350;hs11:35907006-35907006,hs11:38344575-38344575;hs11:35972621-35972621,hs11:104334901-104334901;hs11:36147212-36147212,hs11:131738954-131738954;hs11:36705927-36705927,hs11:133053989-133053989;hs11:37092847-37092847,hs11:46421143-46421143;hs11:37182343-37182343,hs11:38771827-38771827;hs11:37191206-37191206,hs11:56756206-56756206;hs11:37294515-37294515,hs11:57055195-57055195;hs11:37705249-37705249,hs11:112722654-112722654;hs11:38297001-38297001,hs11:107439727-107439727;hs11:38850816-38850816,hs11:70440055-70440055;hs11:38919625-38919625,hs11:40834478-40834478;hs11:38943159-38943159,hs11:80544478-80544478;hs11:39115746-39115746,hs11:89930321-89930321;hs11:40151969-40151969,hs11:49043152-49043152;hs11:40186757-40186757,hs11:47419306-47419306;hs11:40263258-40263258,hs11:83331390-83331390;hs11:40440795-40440795,hs11:55377128-55377128;hs11:40442619-40442619,hs11:105368919-105368919;hs11:40492071-40492071,hs11:87146055-87146055;hs11:40610079-40610079,hs11:41010465-41010465;hs11:41409007-41409007,hs11:77884654-77884654;hs11:41423401-41423401,hs11:118801504-118801504;hs11:41423400-41423400,hs11:118801504-118801504;hs11:41426025-41426025,hs11:79826889-79826889;hs11:41457198-41457198,hs11:81917096-81917096;hs11:41522197-41522197,hs11:59699358-59699358;hs11:41523428-41523428,hs11:63626245-63626245;hs11:41561852-41561852,hs11:101214555-101214555;hs11:41896003-41896003,hs11:73710015-73710015;hs11:41911815-41911815,hs11:67146315-67146315;hs11:42239207-42239207,hs11:116284940-116284940;hs11:42283978-42283978,hs11:88839480-88839480;hs11:42367707-42367707,hs11:88441636-88441636;hs11:42549402-42549402,hs11:103608160-103608160;hs11:42763346-42763346,hs11:92702435-92702435;hs11:42934690-42934690,hs11:84269773-84269773;hs11:43523560-43523560,hs11:68965797-68965797;hs11:43590964-43590964,hs11:87829924-87829924;hs11:43613441-43613441,hs11:67757860-67757860;hs11:43705157-43705157,hs11:126428702-126428702;hs11:43730422-43730422,hs11:49278103-49278103;hs11:43734126-43734126,hs11:85664038-85664038;hs11:43996432-43996432,hs11:67850796-67850796;hs11:44059354-44059354,hs11:86920089-86920089;hs11:44062027-44062027,hs11:77497192-77497192;hs11:44382509-44382509,hs11:69487582-69487582;hs11:44428387-44428387,hs11:63795295-63795295;hs11:44598588-44598588,hs11:129618343-129618343;hs11:44611704-44611704,hs11:63730104-63730104;hs11:44948598-44948598,hs11:46963592-46963592;hs11:44977809-44977809,hs11:71019995-71019995;hs11:45182613-45182613,hs11:62365614-62365614;hs11:45432032-45432032,hs11:61503731-61503731;hs11:45998372-45998372,hs11:124179035-124179035;hs11:45999320-45999320,hs11:96045217-96045217;hs11:46075240-46075240,hs11:64392612-64392612;hs11:46081327-46081327,hs11:82514405-82514405;hs11:46712204-46712204,hs11:112793221-112793221;hs11:46850616-46850616,hs11:85946690-85946690;hs11:46865653-46865653,hs11:75009967-75009967;hs11:46955805-46955805,hs11:83561939-83561939;hs11:47012685-47012685,hs11:82573161-82573161;hs11:47070574-47070574,hs11:62375719-62375719;hs11:47445083-47445083,hs11:76855426-76855426;hs11:47581104-47581104,hs11:124962587-124962587;hs11:47630283-47630283,hs11:78386160-78386160;hs11:47714697-47714697,hs11:105857327-105857327;hs11:48080217-48080217,hs11:105653650-105653650;hs11:48139784-48139784,hs11:61487733-61487733;hs11:48431936-48431936,hs11:48834927-48834927;hs11:49177360-49177360,hs11:125126679-125126679;hs11:49220458-49220458,hs11:133701222-133701222;hs11:49401998-49401998,hs11:86183214-86183214;hs11:50381315-50381315,hs11:103121030-103121030;hs11:50451032-50451032,hs11:81601994-81601994;hs11:55629242-55629242,hs11:113070388-113070388;hs11:55803692-55803692,hs11:82889940-82889940;hs11:55841809-55841809,hs11:85910683-85910683;hs11:56244878-56244878,hs11:80239672-80239672;hs11:56328369-56328369,hs11:99914018-99914018;hs11:56329780-56329780,hs11:110826219-110826219;hs11:56351859-56351859,hs11:73314929-73314929;hs11:56376836-56376836,hs11:104055943-104055943;hs11:56604026-56604026,hs11:102937465-102937465;hs11:56607133-56607133,hs11:86031169-86031169;hs11:56720296-56720296,hs11:110487250-110487250;hs11:57256695-57256695,hs11:131315433-131315433;hs11:57283880-57283880,hs11:61924582-61924582;hs11:57424494-57424494,hs11:96467042-96467042;hs11:57919568-57919568,hs11:94170693-94170693;hs11:58500004-58500004,hs11:65034351-65034351;hs11:58838242-58838242,hs11:71521525-71521525;hs11:59527025-59527025,hs11:65184726-65184726;hs11:59596455-59596455,hs11:126133358-126133358;hs11:60629611-60629611,hs11:73976242-73976242;hs11:60703665-60703665,hs11:94474274-94474274;hs11:60773700-60773700,hs11:68120232-68120232;hs11:60894885-60894885,hs11:120528783-120528783;hs11:60908824-60908824,hs11:129996427-129996427;hs11:61086380-61086380,hs11:71877550-71877550;hs11:61126433-61126433,hs11:79830000-79830000;hs11:61163467-61163467,hs11:62461581-62461581;hs11:61177679-61177679,hs11:131333539-131333539;hs11:61614293-61614293,hs11:62609610-62609610;hs11:61701874-61701874,hs11:70209675-70209675;hs11:61852863-61852863,hs11:81831540-81831540;hs11:61853738-61853738,hs11:132263056-132263056;hs11:62185768-62185768,hs11:121160325-121160325;hs11:62389603-62389603,hs11:122923514-122923514;hs11:62512922-62512922,hs11:105439052-105439052;hs11:62605930-62605930,hs11:114568112-114568112;hs11:62624963-62624963,hs11:128987106-128987106;hs11:62638213-62638213,hs11:119574870-119574870;hs11:62941152-62941152,hs11:64708851-64708851;hs11:63255477-63255477,hs11:108710367-108710367;hs11:63432808-63432808,hs11:130025545-130025545;hs11:63643889-63643889,hs11:126203352-126203352;hs11:63728568-63728568,hs11:114598567-114598567;hs11:64024929-64024929,hs11:65121257-65121257;hs11:64176200-64176200,hs11:117141045-117141045;hs11:64436416-64436416,hs11:69692208-69692208;hs11:64453731-64453731,hs11:126333612-126333612;hs11:64476074-64476074,hs11:134106277-134106277;hs11:64617441-64617441,hs11:104100142-104100142;hs11:64646110-64646110,hs11:114848537-114848537;hs11:64752281-64752281,hs11:95437961-95437961;hs11:65312906-65312906,hs11:71016876-71016876;hs11:65348256-65348256,hs11:93981907-93981907;hs11:65648662-65648662,hs11:117387814-117387814;hs11:65649717-65649717,hs11:132588256-132588256;hs11:65680140-65680140,hs11:71117543-71117543;hs11:65814995-65814995,hs11:70955847-70955847;hs11:65877436-65877436,hs11:94939306-94939306;hs11:66064061-66064061,hs11:105670864-105670864;hs11:66067593-66067593,hs11:74322376-74322376;hs11:66350114-66350114,hs11:79481875-79481875;hs11:66423606-66423606,hs11:69691254-69691254;hs11:66518546-66518546,hs11:66607850-66607850;hs11:66532361-66532361,hs11:95886894-95886894;hs11:66576201-66576201,hs11:93418228-93418228;hs11:66917733-66917733,hs11:100410602-100410602;hs11:66961327-66961327,hs11:134231706-134231706;hs11:67120532-67120532,hs11:127685535-127685535;hs11:67467948-67467948,hs11:71273891-71273891;hs11:67511776-67511776,hs11:134274849-134274849;hs11:67590734-67590734,hs11:124420386-124420386;hs11:67884518-67884518,hs11:101182131-101182131;hs11:67955752-67955752,hs11:103373398-103373398;hs11:67992887-67992887,hs11:105327450-105327450;hs11:68124251-68124251,hs11:109283864-109283864;hs11:68142602-68142602,hs11:96011847-96011847;hs11:68151552-68151552,hs11:68181548-68181548;hs11:68286140-68286140,hs11:86457646-86457646;hs11:68347357-68347357,hs11:98779990-98779990;hs11:68555182-68555182,hs11:71783397-71783397;hs11:68723193-68723193,hs11:113976253-113976253;hs11:68962956-68962956,hs11:122877188-122877188;hs11:69491299-69491299,hs11:81703339-81703339;hs11:70162817-70162817,hs11:104968307-104968307;hs11:70781461-70781461,hs11:109026849-109026849;hs11:70931961-70931961,hs11:101111618-101111618;hs11:71044291-71044291,hs11:134266403-134266403;hs11:71597837-71597837,hs11:95703184-95703184;hs11:72092445-72092445,hs11:84357592-84357592;hs11:72465969-72465969,hs11:125257076-125257076;hs11:72552652-72552652,hs11:80684967-80684967;hs11:72598862-72598862,hs11:129599297-129599297;hs11:72748083-72748083,hs11:81069603-81069603;hs11:73425232-73425232,hs11:74269354-74269354;hs11:73578193-73578193,hs11:95881989-95881989;hs11:73904603-73904603,hs11:101649299-101649299;hs11:74352522-74352522,hs11:79713515-79713515;hs11:74533050-74533050,hs11:114015936-114015936;hs11:75016793-75016793,hs11:117103243-117103243;hs11:75103373-75103373,hs11:117321700-117321700;hs11:75148189-75148189,hs11:124057213-124057213;hs11:76080934-76080934,hs11:100929460-100929460;hs11:76195698-76195698,hs11:110858946-110858946;hs11:76437425-76437425,hs11:86516007-86516007;hs11:76654948-76654948,hs11:83532421-83532421;hs11:76781391-76781391,hs11:88705076-88705076;hs11:76829071-76829071,hs11:77596425-77596425;hs11:76915819-76915819,hs11:132282646-132282646;hs11:77494130-77494130,hs11:80663142-80663142;hs11:77502760-77502760,hs11:109686831-109686831;hs11:78826415-78826415,hs11:103601657-103601657;hs11:80024872-80024872,hs11:93595074-93595074;hs11:80182281-80182281,hs11:116200460-116200460;hs11:80213691-80213691,hs11:85258739-85258739;hs11:80628709-80628709,hs11:88678287-88678287;hs11:80679119-80679119,hs11:94514050-94514050;hs11:81926047-81926047,hs11:85469253-85469253;hs11:84315556-84315556,hs11:123323653-123323653;hs11:84584345-84584345,hs11:94603851-94603851;hs11:85261322-85261322,hs11:98176042-98176042;hs11:85321006-85321006,hs11:128928895-128928895;hs11:85498876-85498876,hs11:128544790-128544790;hs11:86561999-86561999,hs11:109961549-109961549;hs11:87064436-87064436,hs11:125249540-125249540;hs11:87211996-87211996,hs11:87285906-87285906;hs11:87214563-87214563,hs11:98587460-98587460;hs11:87237914-87237914,hs11:105442483-105442483;hs11:87317511-87317511,hs11:116812407-116812407;hs11:87325943-87325943,hs11:90093362-90093362;hs11:88286838-88286838,hs11:105900301-105900301;hs11:88707668-88707668,hs11:133529642-133529642;hs11:89969947-89969947,hs11:100388818-100388818;hs11:90835376-90835376,hs11:109586691-109586691;hs11:91404558-91404558,hs11:103390712-103390712;hs11:91609885-91609885,hs11:98719753-98719753;hs11:92107362-92107362,hs11:132603414-132603414;hs11:92173489-92173489,hs11:95529487-95529487;hs11:92369469-92369469,hs11:109192470-109192470;hs11:93371999-93371999,hs11:98158991-98158991;hs11:93427620-93427620,hs11:110252131-110252131;hs11:93570094-93570094,hsX:108915264-108915264;hs11:93979265-93979265,hs11:104823804-104823804;hs11:94734356-94734356,hs11:133595376-133595376;hs11:94871792-94871792,hs11:103600614-103600614;hs11:95976475-95976475,hs11:116120635-116120635;hs11:96511218-96511218,hs11:105730517-105730517;hs11:96514093-96514093,hs11:132862209-132862209;hs11:96663965-96663965,hs11:120596706-120596706;hs11:98345344-98345344,hs11:126656962-126656962;hs11:98692677-98692677,hs11:130058619-130058619;hs11:98693082-98693082,hs11:126198379-126198379;hs11:98704456-98704456,hs11:115112297-115112297;hs11:99337132-99337132,hs11:128162997-128162997;hs11:99894889-99894889,hs11:113967825-113967825;hs11:100129344-100129344,hs11:118737165-118737165;hs11:100130862-100130862,hs11:111952491-111952491;hs11:100187607-100187607,hs11:108048270-108048270;hs11:100615526-100615526,hs11:114945769-114945769;hs11:101038975-101038975,hs11:121143522-121143522;hs11:101452172-101452172,hs11:114693813-114693813;hs11:101591794-101591794,hs11:130145823-130145823;hs11:101828808-101828808,hs11:128832496-128832496;hs11:101849367-101849367,hs11:104209596-104209596;hs11:104097681-104097681,hs11:104811372-104811372;hs11:104341995-104341995,hs11:113865788-113865788;hs11:105289629-105289629,hs11:120062061-120062061;hs11:105446708-105446708,hs11:116120481-116120481;hs11:107985540-107985540,hs11:111025602-111025602;hs11:108275789-108275789,hs11:128075407-128075407;hs11:108796371-108796371,hs11:133370379-133370379;hs11:109212588-109212588,hs11:117349580-117349580;hs11:112474182-112474182,hs11:128081703-128081703;hs11:112736171-112736171,hs11:129845693-129845693;hs11:113293931-113293931,hs11:116114766-116114766;hs11:114258891-114258891,hs11:121561866-121561866;hs11:115906555-115906555,hs11:125123759-125123759;hs11:117346523-117346523,hs11:131600517-131600517;hs11:117693780-117693780,hs11:120172394-120172394;hs11:118374915-118374915,hs11:134015801-134015801;hs11:118758831-118758831,hs11:121064217-121064217;hs11:119346720-119346720,hs11:126334606-126334606;hs11:124895079-124895079,hs11:134825760-134825760;hs11:125502099-125502099,hs11:126128248-126128248;hs11:125715147-125715147,hs11:134533852-134533852;hs14:96959940-96959940,hs14:103043505-103043505 We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73DeltaEx2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer. GRCh37/hg19 NA CTDB0433 Research 26168399 George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, Leenders F, Lu X, Fernandez-Cuesta L, Bosco G, Muller C, Dahmen I, Jahchan NS, Park KS, Yang D, Karnezis AN, Vaka D, Torres A, Wang MS, Korbel JO, Menon R, Chun SM, Kim D, Wilkerson M, Hayes N, Engelmann D, Putzer B, Bos M, Michels S, Vlasic I, Seidel D, Pinther B, Schaub P, Becker C, Altmuller J, Yokota J, Kohno T, Iwakawa R, Tsuta K, Noguchi M, Muley T, Hoffmann H, Schnabel PA, Petersen I, Chen Y, Soltermann A, Tischler V, Choi CM, Kim YH, Massion PP, Zou Y, Jovanovic D, Kontic M, Wright GM, Russell PA, Solomon B, Koch I, Lindner M, Muscarella LA, la Torre A, Field JK, Jakopovic M, Knezevic J, Castanos-Velez E, Roz L, Pastorino U, Brustugun OT, Lund-Iversen M, Thunnissen E, Kohler J, Schuler M, Botling J, Sandelin M, Sanchez-Cespedes M, Salvesen HB, Achter V, Lang U, Bogus M, Schneider PM, Zander T, Ansen S, Hallek M, Wolf J, Vingron M, Yatabe Y, Travis WD, Nurnberg P, Reinhardt C, Perner S, Heukamp L, Buttner R, Haas SA, Brambilla E, Peifer M, Sage J, Thomas RK Comprehensive genomic profiles of small cell lung cancer Nature 2015 Aug 3,11 Small cell lung cancers Next Generation Sequencing Homo sapiens S02353 Illumina HiSeq 2000 hs1:766596-766596,hs1:769111-769111;hs1:142715155-142715155,hs3:118892073-118892073;hs1:142837693-142837693,hs3:142388477-142388477;hs1:143485074-143485074,hs3:151674668-151674668;hs2:196128035-196128035,hs11:69396215-69396215;hs2:196128000-196128000,hs2:197097571-197097571;hs2:196230866-196230866,hs3:105471230-105471230;hs2:196233144-196233144,hs11:100997955-100997955;hs2:196303039-196303039,hs3:189471659-189471659;hs2:196314898-196314898,hs3:56269676-56269676;hs2:196327220-196327220,hs3:131296582-131296582;hs2:196334316-196334316,hs11:60385918-60385918;hs2:196343670-196343670,hs11:23955078-23955078;hs2:196362638-196362638,hs3:189953375-189953375;hs2:196382288-196382288,hs11:129299940-129299940;hs2:196440100-196440100,hs11:30289132-30289132;hs2:196442305-196442305,hs3:159646143-159646143;hs2:196494680-196494680,hs11:26053521-26053521;hs2:196542884-196542884,hs3:90048441-90048441;hs2:196569214-196569214,hs3:17472700-17472700;hs2:196585982-196585982,hs11:25405151-25405151;hs2:196590367-196590367,hs3:115216059-115216059;hs2:196738880-196738880,hs3:195360051-195360051;hs2:196742093-196742093,hs3:183681943-183681943;hs2:196777360-196777360,hs3:39674183-39674183;hs2:196882306-196882306,hs11:110763531-110763531;hs2:196892388-196892388,hs3:29343207-29343207;hs2:197606299-197606299,hs11:112105148-112105148;hs3:73286-73286,hs3:120460204-120460204;hs3:111967-111967,hs11:124601790-124601790;hs3:120657-120657,hs3:32117570-32117570;hs3:128446-128446,hs3:178986504-178986504;hs3:169550-169550,hs3:148112247-148112247;hs3:195205-195205,hs3:106222847-106222847;hs3:202866-202866,hs11:132792486-132792486;hs3:248167-248167,hs3:127399032-127399032;hs3:253986-253986,hs3:39425398-39425398;hs3:328959-328959,hs3:66910298-66910298;hs3:407407-407407,hs11:108642515-108642515;hs3:418303-418303,hs3:101213331-101213331;hs3:422298-422298,hs3:158810148-158810148;hs3:424113-424113,hs11:131225339-131225339;hs3:429534-429534,hs3:152608133-152608133;hs3:462175-462175,hs3:153109085-153109085;hs3:639398-639398,hs3:113055209-113055209;hs3:711869-711869,hs3:88663488-88663488;hs3:714378-714378,hs3:118288065-118288065;hs3:819507-819507,hs3:59703071-59703071;hs3:890204-890204,hs11:89020923-89020923;hs3:890430-890430,hs3:21554423-21554423;hs3:890430-890430,hs3:21554424-21554424;hs3:977103-977103,hs11:42575177-42575177;hs3:980023-980023,hs3:129606108-129606108;hs3:1034603-1034603,hs3:167990570-167990570;hs3:1064362-1064362,hs3:81824152-81824152;hs3:1077788-1077788,hs3:1629932-1629932;hs3:1084518-1084518,hs3:108230422-108230422;hs3:1086024-1086024,hs3:22757708-22757708;hs3:1105413-1105413,hs11:39183998-39183998;hs3:1209715-1209715,hs3:113800531-113800531;hs3:1285364-1285364,hs3:29915659-29915659;hs3:1388840-1388840,hs3:127021233-127021233;hs3:1432069-1432069,hs3:31210968-31210968;hs3:1623332-1623332,hs11:26138802-26138802;hs3:1625753-1625753,hs3:10279813-10279813;hs3:1735617-1735617,hs11:14411136-14411136;hs3:1757837-1757837,hs3:43191302-43191302;hs3:1926760-1926760,hs11:40823303-40823303;hs3:1934747-1934747,hs3:169654283-169654283;hs3:1935930-1935930,hs11:58242097-58242097;hs3:1942300-1942300,hs3:7254222-7254222;hs3:1984093-1984093,hs3:39584000-39584000;hs3:2007256-2007256,hs3:43664602-43664602;hs3:2013638-2013638,hs3:134437374-134437374;hs3:2150077-2150077,hs3:50880024-50880024;hs3:2199902-2199902,hs3:27183008-27183008;hs3:2296249-2296249,hs3:84163314-84163314;hs3:2368442-2368442,hs3:112084409-112084409;hs3:2409104-2409104,hs11:89472096-89472096;hs3:2411830-2411830,hs3:112529423-112529423;hs3:2474901-2474901,hs3:6460847-6460847;hs3:2483931-2483931,hs3:62091982-62091982;hs3:2550370-2550370,hs11:19955504-19955504;hs3:2553177-2553177,hs11:83423441-83423441;hs3:2603629-2603629,hs11:19372382-19372382;hs3:2692254-2692254,hs11:44964706-44964706;hs3:2705114-2705114,hs11:130407848-130407848;hs3:2711806-2711806,hs3:124529256-124529256;hs3:2758003-2758003,hs3:169720155-169720155;hs3:2777079-2777079,hs3:146605187-146605187;hs3:2790009-2790009,hs11:65279502-65279502;hs3:2867951-2867951,hs3:89960699-89960699;hs3:2887867-2887867,hs3:94015980-94015980;hs3:2890994-2890994,hs3:67639825-67639825;hs3:2900358-2900358,hs3:133140894-133140894;hs3:2921685-2921685,hs11:108034294-108034294;hs3:2928143-2928143,hs3:26066364-26066364;hs3:2954904-2954904,hs3:8357181-8357181;hs3:2971927-2971927,hs11:82052891-82052891;hs3:3033938-3033938,hs3:163757723-163757723;hs3:3042875-3042875,hs11:38540582-38540582;hs3:3221645-3221645,hs3:59500441-59500441;hs3:3226435-3226435,hs11:11320908-11320908;hs3:3255620-3255620,hs3:193004098-193004098;hs3:3259044-3259044,hs3:55383198-55383198;hs3:3381960-3381960,hs11:118279918-118279918;hs3:3406462-3406462,hs11:103779755-103779755;hs3:3414565-3414565,hs11:48330112-48330112;hs3:3489223-3489223,hs21:10961231-10961231;hs3:3494446-3494446,hs3:30279710-30279710;hs3:3602896-3602896,hs11:34177069-34177069;hs3:3617469-3617469,hs3:155086523-155086523;hs3:3618396-3618396,hs3:5179793-5179793;hs3:3622131-3622131,hs3:110867361-110867361;hs3:3666357-3666357,hs11:84364114-84364114;hs3:3740240-3740240,hs11:100177176-100177176;hs3:3744329-3744329,hs3:122779284-122779284;hs3:3762108-3762108,hs11:105160396-105160396;hs3:3788407-3788407,hs11:127635438-127635438;hs3:3794175-3794175,hs3:14323443-14323443;hs3:3807853-3807853,hs3:49783899-49783899;hs3:3858305-3858305,hs3:69475295-69475295;hs3:3929766-3929766,hs11:111716354-111716354;hs3:3961638-3961638,hs3:31102360-31102360;hs3:4013131-4013131,hs11:35058540-35058540;hs3:4065047-4065047,hs11:83787051-83787051;hs3:4072347-4072347,hs11:90714695-90714695;hs3:4088050-4088050,hs11:96185807-96185807;hs3:4095833-4095833,hs11:9674983-9674983;hs3:4268982-4268982,hs3:177138275-177138275;hs3:4304832-4304832,hs3:130575620-130575620;hs3:4404359-4404359,hs11:106886924-106886924;hs3:4412602-4412602,hs11:132228493-132228493;hs3:4701330-4701330,hs11:17370231-17370231;hs3:4706202-4706202,hs3:130622084-130622084;hs3:4707638-4707638,hs3:173340089-173340089;hs3:4750046-4750046,hs3:65767273-65767273;hs3:4753897-4753897,hs11:110350743-110350743;hs3:4789029-4789029,hs3:31641288-31641288;hs3:4810375-4810375,hs3:140689397-140689397;hs3:4819678-4819678,hs11:97148233-97148233;hs3:5134587-5134587,hs3:180791760-180791760;hs3:5177361-5177361,hs11:46790503-46790503;hs3:5183294-5183294,hs3:85593783-85593783;hs3:5232252-5232252,hs3:189562302-189562302;hs3:5243547-5243547,hs3:132578678-132578678;hs3:5246809-5246809,hs3:110772386-110772386;hs3:5270243-5270243,hs3:188473174-188473174;hs3:5312394-5312394,hs3:196237371-196237371;hs3:5572117-5572117,hs11:9256418-9256418;hs3:5583023-5583023,hs3:42079318-42079318;hs3:5620609-5620609,hs3:121843693-121843693;hs3:5675193-5675193,hs3:169480863-169480863;hs3:5827213-5827213,hs11:122632552-122632552;hs3:5845349-5845349,hs11:80562841-80562841;hs3:5954033-5954033,hs3:19492898-19492898;hs3:5959192-5959192,hs3:39840903-39840903;hs3:5998625-5998625,hs11:84679553-84679553;hs3:6025845-6025845,hs3:137058160-137058160;hs3:6042733-6042733,hs3:193069842-193069842;hs3:6084502-6084502,hs3:29068667-29068667;hs3:6149653-6149653,hs3:157256467-157256467;hs3:6161545-6161545,hs3:168442099-168442099;hs3:6434257-6434257,hs3:154080721-154080721;hs3:6465163-6465163,hs3:66393788-66393788;hs3:6560481-6560481,hs3:118538198-118538198;hs3:6582823-6582823,hs11:125760206-125760206;hs3:6603783-6603783,hs11:114370064-114370064;hs3:6648402-6648402,hs11:98662838-98662838;hs3:6650769-6650769,hs11:15300911-15300911;hs3:6689402-6689402,hs11:43284264-43284264;hs3:6691575-6691575,hs3:192418672-192418672;hs3:6743162-6743162,hs3:152001143-152001143;hs3:6769189-6769189,hs3:149395208-149395208;hs3:6773319-6773319,hs11:21555272-21555272;hs3:6853735-6853735,hs11:34230301-34230301;hs3:6914805-6914805,hs3:62687737-62687737;hs3:6955700-6955700,hs3:76603442-76603442;hs3:7084521-7084521,hs3:34848194-34848194;hs3:7118321-7118321,hs11:47262153-47262153;hs3:7204113-7204113,hs3:106400280-106400280;hs3:7287072-7287072,hs3:106910578-106910578;hs3:7296564-7296564,hs3:24984716-24984716;hs3:7653683-7653683,hs3:156258379-156258379;hs3:8031236-8031236,hs3:19684358-19684358;hs3:8044641-8044641,hs11:90951342-90951342;hs3:8082154-8082154,hs3:50888273-50888273;hs3:8088307-8088307,hs11:83295391-83295391;hs3:8177940-8177940,hs11:104519783-104519783;hs3:8179191-8179191,hs11:90977639-90977639;hs3:8198948-8198948,hs3:27142725-27142725;hs3:8259773-8259773,hs11:9221656-9221656;hs3:8299443-8299443,hs3:142945366-142945366;hs3:8311719-8311719,hs3:147784155-147784155;hs3:8388131-8388131,hs3:109799958-109799958;hs3:8424333-8424333,hs11:35591450-35591450;hs3:8465472-8465472,hs11:50123375-50123375;hs3:8500040-8500040,hs3:124559950-124559950;hs3:8523002-8523002,hs11:38642844-38642844;hs3:8543343-8543343,hs3:13660544-13660544;hs3:8622742-8622742,hs3:95722166-95722166;hs3:8629840-8629840,hs11:6332274-6332274;hs3:8678575-8678575,hs11:38837594-38837594;hs3:8715001-8715001,hs11:134904126-134904126;hs3:8728206-8728206,hs3:156278833-156278833;hs3:8738718-8738718,hs11:31076446-31076446;hs3:8753887-8753887,hs3:193202636-193202636;hs3:8755961-8755961,hs11:7836781-7836781;hs3:8880979-8880979,hs11:14695259-14695259;hs3:8897761-8897761,hs11:77224857-77224857;hs3:8913091-8913091,hs3:161354075-161354075;hs3:8939104-8939104,hs3:60224464-60224464;hs3:9000391-9000391,hs11:111967477-111967477;hs3:9111064-9111064,hs3:40107446-40107446;hs3:9132520-9132520,hs3:114939335-114939335;hs3:9162079-9162079,hs3:45404762-45404762;hs3:9184894-9184894,hs3:116403164-116403164;hs3:9191018-9191018,hs11:57234385-57234385;hs3:9227727-9227727,hs11:128609330-128609330;hs3:9282309-9282309,hs11:87218375-87218375;hs3:9326323-9326323,hs11:68284487-68284487;hs3:9351807-9351807,hs3:86411438-86411438;hs3:9361590-9361590,hs11:68830673-68830673;hs3:9368325-9368325,hs3:114704048-114704048;hs3:9373565-9373565,hs11:80668572-80668572;hs3:9457139-9457139,hs3:40159343-40159343;hs3:9463548-9463548,hs3:175587932-175587932;hs3:9527853-9527853,hs3:124229181-124229181;hs3:9572211-9572211,hs11:27765887-27765887;hs3:9585080-9585080,hs11:12490861-12490861;hs3:9594413-9594413,hs11:97049456-97049456;hs3:9604445-9604445,hs3:84991747-84991747;hs3:9607471-9607471,hs3:164694521-164694521;hs3:9619719-9619719,hs11:39518908-39518908;hs3:9709985-9709985,hs11:16361396-16361396;hs3:9711797-9711797,hs3:164286373-164286373;hs3:9740627-9740627,hs11:11433526-11433526;hs3:9812858-9812858,hs11:8681050-8681050;hs3:9842777-9842777,hs3:172963544-172963544;hs3:9850043-9850043,hs11:59438206-59438206;hs3:9863913-9863913,hs3:188109129-188109129;hs3:9864693-9864693,hs3:56933306-56933306;hs3:9957058-9957058,hs3:41663604-41663604;hs3:10144402-10144402,hs3:30815024-30815024;hs3:10229335-10229335,hs3:186655405-186655405;hs3:10236873-10236873,hs3:24187015-24187015;hs3:10238750-10238750,hs3:39460205-39460205;hs3:10289182-10289182,hs3:137671650-137671650;hs3:10317325-10317325,hs3:144633790-144633790;hs3:10317694-10317694,hs3:119280038-119280038;hs3:10320448-10320448,hs11:18261591-18261591;hs3:10539761-10539761,hs3:40558756-40558756;hs3:10561184-10561184,hs3:16531309-16531309;hs3:10702101-10702101,hs3:21724986-21724986;hs3:10709671-10709671,hs3:175487605-175487605;hs3:10755587-10755587,hs3:82544608-82544608;hs3:10760133-10760133,hs3:47450058-47450058;hs3:10825944-10825944,hs3:113027148-113027148;hs3:10910651-10910651,hs11:20926730-20926730;hs3:10962816-10962816,hs11:124549984-124549984;hs3:10989075-10989075,hs3:13478889-13478889;hs3:11176423-11176423,hs11:64740500-64740500;hs3:11231871-11231871,hs11:40154974-40154974;hs3:11239030-11239030,hs11:28459908-28459908;hs3:11338219-11338219,hs3:143301217-143301217;hs3:11346285-11346285,hs3:130721442-130721442;hs3:11426396-11426396,hs3:148462405-148462405;hs3:11440245-11440245,hs3:166885614-166885614;hs3:11444158-11444158,hs3:129861719-129861719;hs3:11449171-11449171,hs11:38617809-38617809;hs3:11476285-11476285,hs3:122756659-122756659;hs3:11584737-11584737,hs11:31833137-31833137;hs3:11594860-11594860,hs11:95030420-95030420;hs3:11650119-11650119,hs3:33552147-33552147;hs3:11713808-11713808,hs3:71262567-71262567;hs3:11809792-11809792,hs3:168907000-168907000;hs3:11851340-11851340,hs3:69168566-69168566;hs3:11942983-11942983,hs12:112136939-112136939;hs3:12104596-12104596,hs3:109498879-109498879;hs3:12150453-12150453,hs11:116916567-116916567;hs3:12263419-12263419,hs11:66327611-66327611;hs3:12265186-12265186,hs3:145919442-145919442;hs3:12322880-12322880,hs3:188403420-188403420;hs3:12329759-12329759,hs3:45230542-45230542;hs3:12382906-12382906,hs3:47761781-47761781;hs3:12394302-12394302,hs11:37701829-37701829;hs3:12506454-12506454,hs11:116768484-116768484;hs3:12510932-12510932,hs3:153689439-153689439;hs3:12510933-12510933,hs3:153689440-153689440;hs3:12518128-12518128,hs3:144791809-144791809;hs3:12617441-12617441,hs11:124533799-124533799;hs3:12640152-12640152,hs11:65537347-65537347;hs3:12643176-12643176,hs3:127426616-127426616;hs3:12716081-12716081,hs11:109738320-109738320;hs3:12841372-12841372,hs11:132809727-132809727;hs3:12847717-12847717,hs11:40051705-40051705;hs3:12849629-12849629,hs3:178414096-178414096;hs3:12857083-12857083,hs3:186246067-186246067;hs3:12917142-12917142,hs3:79067795-79067795;hs3:12950135-12950135,hs11:80123933-80123933;hs3:12954927-12954927,hs3:154636066-154636066;hs3:12961111-12961111,hs3:183305292-183305292;hs3:12970490-12970490,hs11:106814531-106814531;hs3:12980106-12980106,hs11:67270378-67270378;hs3:12985135-12985135,hs3:152887446-152887446;hs3:12985414-12985414,hs11:96172922-96172922;hs3:13022180-13022180,hs11:133952573-133952573;hs3:13065091-13065091,hs3:28649586-28649586;hs3:13109077-13109077,hs11:44571347-44571347;hs3:13111509-13111509,hs3:157581326-157581326;hs3:13134308-13134308,hs11:59787808-59787808;hs3:13157625-13157625,hs3:120010128-120010128;hs3:13166236-13166236,hs3:193529540-193529540;hs3:13174584-13174584,hs11:23958856-23958856;hs3:13241781-13241781,hs3:125079114-125079114;hs3:13262546-13262546,hs3:188270212-188270212;hs3:13299056-13299056,hs3:20046173-20046173;hs3:13353159-13353159,hs3:132804222-132804222;hs3:13403582-13403582,hs3:157833182-157833182;hs3:13486288-13486288,hs3:23961290-23961290;hs3:13560506-13560506,hs3:67797763-67797763;hs3:13625663-13625663,hs11:44670847-44670847;hs3:13628380-13628380,hs11:65864803-65864803;hs3:13631577-13631577,hs11:15252074-15252074;hs3:13650579-13650579,hs3:83438824-83438824;hs3:13695751-13695751,hs11:76815489-76815489;hs3:13792246-13792246,hs11:39005737-39005737;hs3:13949784-13949784,hs3:113897528-113897528;hs3:13956215-13956215,hs11:3549278-3549278;hs3:13963180-13963180,hs11:11100760-11100760;hs3:13964800-13964800,hs11:12614353-12614353;hs3:13987723-13987723,hs3:84135912-84135912;hs3:14260541-14260541,hs3:83799133-83799133;hs3:14264108-14264108,hs3:183448542-183448542;hs3:14292601-14292601,hs3:57255782-57255782;hs3:14326507-14326507,hs21:9575322-9575322;hs3:14377926-14377926,hs3:52414683-52414683;hs3:14389530-14389530,hs3:184691912-184691912;hs3:14398543-14398543,hs11:111260831-111260831;hs3:14480517-14480517,hs11:134809954-134809954;hs3:14659246-14659246,hs11:1690339-1690339;hs3:14878861-14878861,hs11:112215464-112215464;hs3:14880767-14880767,hs11:103489803-103489803;hs3:14922006-14922006,hs3:29534926-29534926;hs3:14926671-14926671,hs3:23294005-23294005;hs3:14944497-14944497,hs3:84802866-84802866;hs3:14950837-14950837,hs3:188556020-188556020;hs3:14989619-14989619,hs11:66197620-66197620;hs3:15030338-15030338,hs3:160021596-160021596;hs3:15036548-15036548,hs3:83063492-83063492;hs3:15184039-15184039,hs11:100281242-100281242;hs3:15241008-15241008,hs11:66186580-66186580;hs3:15277287-15277287,hs11:85779871-85779871;hs3:15278020-15278020,hs3:40204336-40204336;hs3:15289514-15289514,hs3:61049092-61049092;hs3:15292054-15292054,hs3:120442378-120442378;hs3:15326459-15326459,hs3:28211125-28211125;hs3:15380975-15380975,hs3:45084211-45084211;hs3:15390577-15390577,hs3:114967421-114967421;hs3:15392815-15392815,hs3:168355019-168355019;hs3:15410523-15410523,hs3:177645593-177645593;hs3:15463005-15463005,hs11:115284811-115284811;hs3:15737672-15737672,hs3:45272904-45272904;hs3:15741280-15741280,hs3:179056939-179056939;hs3:15763905-15763905,hs11:107587609-107587609;hs3:15764693-15764693,hs3:111257264-111257264;hs3:15803776-15803776,hs11:117471296-117471296;hs3:15890107-15890107,hs3:142461980-142461980;hs3:15894550-15894550,hs3:36831812-36831812;hs3:15926347-15926347,hs3:74408830-74408830;hs3:15927788-15927788,hs11:97883764-97883764;hs3:16113399-16113399,hs11:64852842-64852842;hs3:16333961-16333961,hs3:28204266-28204266;hs3:16364206-16364206,hs11:126348453-126348453;hs3:16493944-16493944,hs3:103217970-103217970;hs3:16535020-16535020,hs3:17744722-17744722;hs3:16563283-16563283,hs3:54322587-54322587;hs3:16615360-16615360,hs11:65362697-65362697;hs3:16618889-16618889,hs3:131839829-131839829;hs3:16822831-16822831,hs11:41876693-41876693;hs3:16832063-16832063,hs3:128215425-128215425;hs3:16855471-16855471,hs3:136727166-136727166;hs3:16868251-16868251,hs3:196574000-196574000;hs3:16919636-16919636,hs3:132312306-132312306;hs3:16959889-16959889,hs11:104802045-104802045;hs3:17060181-17060181,hs11:127594422-127594422;hs3:17196088-17196088,hs11:44606160-44606160;hs3:17200963-17200963,hs3:182269041-182269041;hs3:17395452-17395452,hs3:146623088-146623088;hs3:17419435-17419435,hs3:126013873-126013873;hs3:17435057-17435057,hs11:130547248-130547248;hs3:17778367-17778367,hs11:131564760-131564760;hs3:17781510-17781510,hs3:93801408-93801408;hs3:17790655-17790655,hs3:125076317-125076317;hs3:17809512-17809512,hs3:60694232-60694232;hs3:17875929-17875929,hs3:112559540-112559540;hs3:17906904-17906904,hs11:88681564-88681564;hs3:17921731-17921731,hs11:117699724-117699724;hs3:17939316-17939316,hs11:19406204-19406204;hs3:17945850-17945850,hs3:66859084-66859084;hs3:18026470-18026470,hs3:151989341-151989341;hs3:18121190-18121190,hs11:20906780-20906780;hs3:18134067-18134067,hs3:31046760-31046760;hs3:18147001-18147001,hs11:40254538-40254538;hs3:18148732-18148732,hs3:78671313-78671313;hs3:18156841-18156841,hs3:150619254-150619254;hs3:18161846-18161846,hs11:130732961-130732961;hs3:18184646-18184646,hs11:1329379-1329379;hs3:18192781-18192781,hs3:162815194-162815194;hs3:18224016-18224016,hs11:42541930-42541930;hs3:18343393-18343393,hs11:9268199-9268199;hs3:18399154-18399154,hs11:130251064-130251064;hs3:18439787-18439787,hs11:22747745-22747745;hs3:18471598-18471598,hs3:87325032-87325032;hs3:18484689-18484689,hs11:134887741-134887741;hs3:18507590-18507590,hs3:28160302-28160302;hs3:18514205-18514205,hs11:20634471-20634471;hs3:18523035-18523035,hs11:93207205-93207205;hs3:18538594-18538594,hs11:17508813-17508813;hs3:18566191-18566191,hs11:133485937-133485937;hs3:18567306-18567306,hs11:68613665-68613665;hs3:18583966-18583966,hs3:108031572-108031572;hs3:18584092-18584092,hs3:181620109-181620109;hs3:18603729-18603729,hs11:127819886-127819886;hs3:18608132-18608132,hs3:66773236-66773236;hs3:18650644-18650644,hs11:125171278-125171278;hs3:18656206-18656206,hs3:41435724-41435724;hs3:18690310-18690310,hs11:109199961-109199961;hs3:18707994-18707994,hs3:119780468-119780468;hs3:18725094-18725094,hs11:60573689-60573689;hs3:18739087-18739087,hs11:85254528-85254528;hs3:18743318-18743318,hs3:139131044-139131044;hs3:18853949-18853949,hs11:107401534-107401534;hs3:18948383-18948383,hs3:97529121-97529121;hs3:18959214-18959214,hs3:136317565-136317565;hs3:18965266-18965266,hs3:96417042-96417042;hs3:19014809-19014809,hs3:139404190-139404190;hs3:19154384-19154384,hs11:66006347-66006347;hs3:19178877-19178877,hs11:66958869-66958869;hs3:19214376-19214376,hs3:39896805-39896805;hs3:19249212-19249212,hs3:30367100-30367100;hs3:19389731-19389731,hs3:147015290-147015290;hs3:19423281-19423281,hs3:30952465-30952465;hs3:19484944-19484944,hs11:62734021-62734021;hs3:19518702-19518702,hs3:35094703-35094703;hs3:19531559-19531559,hs11:107650893-107650893;hs3:19598298-19598298,hs11:92702809-92702809;hs3:19599205-19599205,hs11:115331738-115331738;hs3:19649317-19649317,hs11:99622323-99622323;hs3:19678948-19678948,hs3:162085027-162085027;hs3:19715359-19715359,hs3:176060855-176060855;hs3:19787205-19787205,hs11:102229216-102229216;hs3:19790358-19790358,hs3:120362298-120362298;hs3:19816274-19816274,hs3:156910882-156910882;hs3:19819660-19819660,hs21:10581886-10581886;hs3:19830343-19830343,hs3:81889140-81889140;hs3:19948762-19948762,hs11:38418607-38418607;hs3:20033640-20033640,hs3:31186408-31186408;hs3:20064873-20064873,hs3:154530248-154530248;hs3:20066997-20066997,hs3:73487729-73487729;hs3:20081779-20081779,hs11:3379103-3379103;hs3:20084772-20084772,hs3:29844615-29844615;hs3:20123404-20123404,hs11:45528300-45528300;hs3:20132809-20132809,hs3:30865325-30865325;hs3:20164186-20164186,hs3:104545003-104545003;hs3:20179410-20179410,hs11:33890441-33890441;hs3:20306645-20306645,hs3:45845578-45845578;hs3:20319548-20319548,hs11:125199484-125199484;hs3:20335658-20335658,hs3:71885921-71885921;hs3:20349492-20349492,hs3:151828655-151828655;hs3:20351169-20351169,hs3:119171304-119171304;hs3:20389284-20389284,hs3:94160756-94160756;hs3:20436737-20436737,hs11:85659253-85659253;hs3:20511481-20511481,hs3:165116540-165116540;hs3:20526450-20526450,hs3:166995371-166995371;hs3:20530723-20530723,hs11:110749957-110749957;hs3:20548868-20548868,hs3:50393624-50393624;hs3:20561357-20561357,hs3:80556386-80556386;hs3:20831523-20831523,hs11:21142838-21142838;hs3:20832018-20832018,hs11:38387077-38387077;hs3:20863784-20863784,hs3:52599828-52599828;hs3:20869455-20869455,hs3:106873651-106873651;hs3:20942620-20942620,hs3:108746572-108746572;hs3:20960320-20960320,hs3:54784852-54784852;hs3:20965648-20965648,hs3:40049609-40049609;hs3:20966344-20966344,hs3:48018401-48018401;hs3:20993442-20993442,hs3:116885001-116885001;hs3:21044380-21044380,hs3:118684361-118684361;hs3:21047344-21047344,hs11:134182432-134182432;hs3:21181531-21181531,hs3:38212104-38212104;hs3:21331148-21331148,hs11:115435792-115435792;hs3:21339675-21339675,hs3:191282587-191282587;hs3:21345546-21345546,hs3:125245099-125245099;hs3:21351542-21351542,hs3:164471685-164471685;hs3:21356934-21356934,hs3:67832067-67832067;hs3:21391509-21391509,hs3:89388743-89388743;hs3:21612091-21612091,hs3:174173833-174173833;hs3:21648185-21648185,hs3:165950868-165950868;hs3:21653341-21653341,hs3:109803758-109803758;hs3:21891000-21891000,hs11:106042281-106042281;hs3:22115028-22115028,hs3:117944845-117944845;hs3:22116494-22116494,hs11:37945192-37945192;hs3:22400307-22400307,hs11:95111828-95111828;hs3:22404912-22404912,hs11:122584102-122584102;hs3:22582415-22582415,hs11:67341268-67341268;hs3:22766679-22766679,hs11:26533387-26533387;hs3:22769835-22769835,hs11:50582354-50582354;hs3:22773819-22773819,hs3:79259090-79259090;hs3:22785482-22785482,hs3:195366585-195366585;hs3:22800468-22800468,hs11:38216487-38216487;hs3:22841688-22841688,hs11:37327233-37327233;hs3:22889750-22889750,hs11:18893810-18893810;hs3:22898206-22898206,hs11:78861876-78861876;hs3:23006924-23006924,hs3:161648400-161648400;hs3:23062288-23062288,hs11:99995387-99995387;hs3:23193218-23193218,hs11:114063998-114063998;hs3:23385644-23385644,hs11:22123311-22123311;hs3:23406422-23406422,hs11:92438439-92438439;hs3:23409791-23409791,hs3:65287785-65287785;hs3:23426687-23426687,hs11:123983634-123983634;hs3:23437493-23437493,hs3:180973366-180973366;hs3:23560075-23560075,hs3:155447892-155447892;hs3:23560852-23560852,hs3:98733414-98733414;hs3:23560852-23560852,hs3:98733414-98733414;hs3:23579613-23579613,hs11:21057541-21057541;hs3:23606588-23606588,hs3:146208496-146208496;hs3:23610196-23610196,hs11:353140-353140;hs3:23617453-23617453,hs3:54235937-54235937;hs3:23622465-23622465,hs11:85087348-85087348;hs3:23711008-23711008,hs11:10572517-10572517;hs3:23719779-23719779,hs11:120551135-120551135;hs3:23804735-23804735,hs11:97619508-97619508;hs3:23815597-23815597,hs11:112931634-112931634;hs3:23847136-23847136,hs3:47979163-47979163;hs3:23849061-23849061,hs3:150667239-150667239;hs3:23922007-23922007,hs11:41915885-41915885;hs3:23933464-23933464,hs3:129626411-129626411;hs3:24011276-24011276,hs11:104928779-104928779;hs3:24166408-24166408,hs11:115686541-115686541;hs3:24176326-24176326,hs3:42582063-42582063;hs3:24185640-24185640,hs11:58861552-58861552;hs3:24192590-24192590,hs3:72275244-72275244;hs3:24201304-24201304,hs3:81838282-81838282;hs3:24206389-24206389,hs11:25834073-25834073;hs3:24210006-24210006,hs3:55231035-55231035;hs3:24217479-24217479,hs11:60417975-60417975;hs3:24225826-24225826,hs11:41046261-41046261;hs3:24232953-24232953,hs3:150591190-150591190;hs3:24241483-24241483,hs3:71572279-71572279;hs3:24265934-24265934,hs3:26078126-26078126;hs3:24329373-24329373,hs3:87023056-87023056;hs3:24345674-24345674,hs11:98728368-98728368;hs3:24368014-24368014,hs11:15153939-15153939;hs3:24381638-24381638,hs3:101115293-101115293;hs3:24383496-24383496,hs3:120155469-120155469;hs3:24536391-24536391,hs11:47629555-47629555;hs3:24632052-24632052,hs3:34659102-34659102;hs3:24640413-24640413,hs3:193437688-193437688;hs3:24741245-24741245,hs11:63122405-63122405;hs3:24779647-24779647,hs3:135707723-135707723;hs3:24932907-24932907,hs3:114262803-114262803;hs3:25021531-25021531,hs3:84186292-84186292;hs3:25021532-25021532,hs3:84186292-84186292;hs3:25040547-25040547,hs3:122640541-122640541;hs3:25046463-25046463,hs3:151226374-151226374;hs3:25287727-25287727,hs3:94919095-94919095;hs3:25288978-25288978,hs3:65450963-65450963;hs3:25382423-25382423,hs11:130658936-130658936;hs3:25451702-25451702,hs3:71582793-71582793;hs3:25504681-25504681,hs11:36374467-36374467;hs3:25508697-25508697,hs3:50967080-50967080;hs3:25514487-25514487,hs3:69604320-69604320;hs3:25619649-25619649,hs11:100467604-100467604;hs3:25667826-25667826,hs3:68870131-68870131;hs3:25692920-25692920,hs3:168837377-168837377;hs3:25700561-25700561,hs11:5291572-5291572;hs3:25714440-25714440,hs3:126705927-126705927;hs3:25781734-25781734,hs11:6289007-6289007;hs3:25832953-25832953,hs3:80456202-80456202;hs3:25946192-25946192,hs11:90371526-90371526;hs3:25967975-25967975,hs3:59100625-59100625;hs3:26092010-26092010,hs3:139609175-139609175;hs3:26099776-26099776,hs11:23007910-23007910;hs3:26106623-26106623,hs3:26518122-26518122;hs3:26194144-26194144,hs3:100262440-100262440;hs3:26213170-26213170,hs3:112789671-112789671;hs3:26261926-26261926,hs11:20022590-20022590;hs3:26277205-26277205,hs3:165957655-165957655;hs3:26292396-26292396,hs3:53148389-53148389;hs3:26309815-26309815,hs3:84527399-84527399;hs3:26331462-26331462,hs3:189392080-189392080;hs3:26335498-26335498,hs11:9445005-9445005;hs3:26447176-26447176,hs3:180954496-180954496;hs3:26488872-26488872,hs3:50986447-50986447;hs3:26523361-26523361,hs3:102793636-102793636;hs3:26606486-26606486,hs3:165231068-165231068;hs3:26933141-26933141,hs3:183160934-183160934;hs3:26950034-26950034,hs11:87344973-87344973;hs3:26997314-26997314,hs11:113443071-113443071;hs3:27057992-27057992,hs3:99277573-99277573;hs3:27108539-27108539,hs11:127583448-127583448;hs3:27255315-27255315,hs3:102915961-102915961;hs3:27305685-27305685,hs3:122551650-122551650;hs3:27507870-27507870,hs3:106538466-106538466;hs3:27588891-27588891,hs3:52577198-52577198;hs3:27604938-27604938,hs11:81862955-81862955;hs3:27611722-27611722,hs3:30214194-30214194;hs3:27618719-27618719,hs11:23213085-23213085;hs3:27635066-27635066,hs3:84697224-84697224;hs3:27640964-27640964,hs11:77651770-77651770;hs3:27679135-27679135,hs3:181003514-181003514;hs3:27758549-27758549,hs11:45755683-45755683;hs3:27891498-27891498,hs11:121018961-121018961;hs3:27912847-27912847,hs11:104267065-104267065;hs3:27928362-27928362,hs3:141566576-141566576;hs3:27934423-27934423,hs3:135918647-135918647;hs3:28054723-28054723,hs3:106340582-106340582;hs3:28065440-28065440,hs3:140190869-140190869;hs3:28072775-28072775,hs11:11673127-11673127;hs3:28112823-28112823,hs3:163857630-163857630;hs3:28115356-28115356,hs11:17188016-17188016;hs3:28155990-28155990,hs3:154020758-154020758;hs3:28166974-28166974,hs3:167795340-167795340;hs3:28234921-28234921,hs11:116113902-116113902;hs3:28260541-28260541,hs3:79871995-79871995;hs3:28287746-28287746,hs3:132771740-132771740;hs3:28290215-28290215,hs3:80295944-80295944;hs3:28508782-28508782,hs3:73071189-73071189;hs3:28624361-28624361,hs11:20357660-20357660;hs3:28811231-28811231,hs11:105041461-105041461;hs3:28854053-28854053,hs11:87635642-87635642;hs3:28906275-28906275,hs11:88989572-88989572;hs3:28919955-28919955,hs3:194716211-194716211;hs3:28919954-28919954,hs3:194716211-194716211;hs3:29049586-29049586,hs3:69883222-69883222;hs3:29059796-29059796,hs11:104195115-104195115;hs3:29118678-29118678,hs3:61826485-61826485;hs3:29120418-29120418,hs3:47096597-47096597;hs3:29157671-29157671,hs11:116948457-116948457;hs3:29170456-29170456,hs11:108026325-108026325;hs3:29291263-29291263,hs3:45292331-45292331;hs3:29293887-29293887,hs3:56244220-56244220;hs3:29301262-29301262,hs3:167323808-167323808;hs3:29374323-29374323,hs3:56934227-56934227;hs3:29374322-29374322,hs3:56934227-56934227;hs3:29375130-29375130,hs11:19623668-19623668;hs3:29381228-29381228,hs11:120639921-120639921;hs3:29524362-29524362,hs3:118157983-118157983;hs3:29599056-29599056,hs3:101111731-101111731;hs3:29620066-29620066,hs11:90707444-90707444;hs3:29632872-29632872,hs11:27484765-27484765;hs3:29671053-29671053,hs3:103711347-103711347;hs3:29687132-29687132,hs11:10661802-10661802;hs3:29725424-29725424,hs3:168335492-168335492;hs3:29863045-29863045,hs11:5318701-5318701;hs3:29893966-29893966,hs3:177690411-177690411;hs3:29912624-29912624,hs3:145975854-145975854;hs3:29949792-29949792,hs11:17090845-17090845;hs3:29989113-29989113,hs11:25816192-25816192;hs3:30128907-30128907,hs3:115498112-115498112;hs3:30152496-30152496,hs11:103922525-103922525;hs3:30157464-30157464,hs3:95773251-95773251;hs3:30180300-30180300,hs3:155317977-155317977;hs3:30235728-30235728,hs3:155847615-155847615;hs3:30288664-30288664,hs11:120841091-120841091;hs3:30298670-30298670,hs11:101178795-101178795;hs3:30322292-30322292,hs3:145826449-145826449;hs3:30322497-30322497,hs3:169787807-169787807;hs3:30353501-30353501,hs3:164086348-164086348;hs3:30412117-30412117,hs11:32184902-32184902;hs3:30463879-30463879,hs3:147817175-147817175;hs3:30570693-30570693,hs11:6649887-6649887;hs3:30598321-30598321,hs11:121561376-121561376;hs3:30612848-30612848,hs3:87384418-87384418;hs3:30633850-30633850,hs11:44559001-44559001;hs3:30723519-30723519,hs3:128738289-128738289;hs3:30831575-30831575,hs3:32265843-32265843;hs3:30906465-30906465,hs3:52242792-52242792;hs3:30941866-30941866,hs3:88081561-88081561;hs3:30984213-30984213,hs3:103624040-103624040;hs3:30991566-30991566,hs3:163553250-163553250;hs3:31040898-31040898,hs3:181151445-181151445;hs3:31074531-31074531,hs3:183141629-183141629;hs3:31096379-31096379,hs3:132659109-132659109;hs3:31333830-31333830,hs11:40249875-40249875;hs3:31356409-31356409,hs3:120838439-120838439;hs3:31401525-31401525,hs11:78993008-78993008;hs3:31417885-31417885,hs11:32554431-32554431;hs3:31423721-31423721,hs11:76805986-76805986;hs3:31492183-31492183,hs3:121765948-121765948;hs3:31539737-31539737,hs11:42778353-42778353;hs3:31606323-31606323,hs3:96249012-96249012;hs3:31658394-31658394,hs3:88764900-88764900;hs3:31679965-31679965,hs3:129065053-129065053;hs3:31687142-31687142,hs11:14508102-14508102;hs3:31706160-31706160,hs3:42472175-42472175;hs3:31722783-31722783,hs3:73206979-73206979;hs3:31723147-31723147,hs3:145844936-145844936;hs3:31723560-31723560,hs11:65353282-65353282;hs3:31862416-31862416,hs3:99369311-99369311;hs3:31866470-31866470,hs3:73822669-73822669;hs3:31875630-31875630,hs3:192239469-192239469;hs3:31896932-31896932,hs3:166380101-166380101;hs3:31911821-31911821,hs11:40858093-40858093;hs3:31991018-31991018,hs11:25110061-25110061;hs3:32007483-32007483,hs11:98451977-98451977;hs3:32260892-32260892,hs11:49848393-49848393;hs3:32419824-32419824,hs11:96825996-96825996;hs3:32444661-32444661,hs3:58401070-58401070;hs3:32483061-32483061,hs11:116955732-116955732;hs3:32557922-32557922,hs11:57468441-57468441;hs3:32560194-32560194,hs3:113960692-113960692;hs3:32604442-32604442,hs11:47121953-47121953;hs3:32610262-32610262,hs3:59031646-59031646;hs3:32643633-32643633,hs3:53719742-53719742;hs3:32652085-32652085,hs3:136304525-136304525;hs3:32765022-32765022,hs11:102563492-102563492;hs3:32789650-32789650,hs3:51646467-51646467;hs3:32793954-32793954,hs3:79702818-79702818;hs3:32830725-32830725,hs3:99347032-99347032;hs3:32831656-32831656,hs11:44597752-44597752;hs3:32939782-32939782,hs3:139308538-139308538;hs3:32942757-32942757,hs11:12462816-12462816;hs3:32944462-32944462,hs3:41330035-41330035;hs3:32984699-32984699,hs3:105102413-105102413;hs3:32985648-32985648,hs11:65857254-65857254;hs3:33040436-33040436,hs3:139750725-139750725;hs3:33113158-33113158,hs3:137330348-137330348;hs3:33217931-33217931,hs11:14142693-14142693;hs3:33228735-33228735,hs11:42736359-42736359;hs3:33267957-33267957,hs3:105934201-105934201;hs3:33357598-33357598,hs3:191449357-191449357;hs3:33360760-33360760,hs3:145579497-145579497;hs3:33388756-33388756,hs3:57590269-57590269;hs3:33462933-33462933,hs3:191660562-191660562;hs3:33478190-33478190,hs11:68518250-68518250;hs3:33517262-33517262,hs3:173595377-173595377;hs3:33532895-33532895,hs11:11057482-11057482;hs3:33577447-33577447,hs11:114430964-114430964;hs3:33583852-33583852,hs3:76791144-76791144;hs3:33630905-33630905,hs3:38437387-38437387;hs3:33639960-33639960,hs11:97759695-97759695;hs3:33703111-33703111,hs3:140436522-140436522;hs3:33740600-33740600,hs11:16987892-16987892;hs3:33751074-33751074,hs3:118656576-118656576;hs3:33813920-33813920,hs11:132577739-132577739;hs3:33926745-33926745,hs3:173965211-173965211;hs3:33969293-33969293,hs3:145830675-145830675;hs3:34015857-34015857,hs11:127265652-127265652;hs3:34065880-34065880,hs3:119862377-119862377;hs3:34166167-34166167,hs3:110150851-110150851;hs3:34210447-34210447,hs11:111718569-111718569;hs3:34270957-34270957,hs3:71450389-71450389;hs3:34406362-34406362,hs3:115852531-115852531;hs3:34414285-34414285,hs11:26209903-26209903;hs3:34420371-34420371,hs3:110518011-110518011;hs3:34510736-34510736,hs3:184144637-184144637;hs3:34562803-34562803,hs11:80830058-80830058;hs3:34632700-34632700,hs11:48619657-48619657;hs3:34647077-34647077,hs3:114520346-114520346;hs3:34652819-34652819,hs11:37985862-37985862;hs3:34654093-34654093,hs3:123384482-123384482;hs3:34735577-34735577,hs11:132211328-132211328;hs3:34740964-34740964,hs11:100742199-100742199;hs3:34750443-34750443,hs3:84789983-84789983;hs3:34845118-34845118,hs3:168368966-168368966;hs3:34902490-34902490,hs3:55944770-55944770;hs3:34964213-34964213,hs3:79689237-79689237;hs3:34980531-34980531,hs11:83711038-83711038;hs3:35050988-35050988,hs3:155583359-155583359;hs3:35069562-35069562,hs11:123796688-123796688;hs3:35097123-35097123,hs3:56424486-56424486;hs3:35217361-35217361,hs3:83802733-83802733;hs3:35285143-35285143,hs3:69044053-69044053;hs3:35309014-35309014,hs11:48807331-48807331;hs3:35337094-35337094,hs11:24197978-24197978;hs3:35406265-35406265,hs3:112093279-112093279;hs3:35470698-35470698,hs3:147938106-147938106;hs3:35515012-35515012,hs3:116172463-116172463;hs3:35620141-35620141,hs11:15980564-15980564;hs3:35667209-35667209,hs11:84707850-84707850;hs3:35710695-35710695,hs3:108844149-108844149;hs3:35716110-35716110,hs11:94707667-94707667;hs3:35786541-35786541,hs11:16734278-16734278;hs3:35922128-35922128,hs3:58203508-58203508;hs3:35947821-35947821,hs3:193239860-193239860;hs3:35977050-35977050,hs11:119876949-119876949;hs3:36094933-36094933,hs3:107783805-107783805;hs3:36101749-36101749,hs11:34022946-34022946;hs3:36115303-36115303,hs3:140843567-140843567;hs3:36116375-36116375,hs11:31098028-31098028;hs3:36142699-36142699,hs11:56056151-56056151;hs3:36252210-36252210,hs3:124602143-124602143;hs3:36308196-36308196,hs3:82621790-82621790;hs3:36312381-36312381,hs3:180456937-180456937;hs3:36356375-36356375,hs11:134372406-134372406;hs3:36495613-36495613,hs11:101184887-101184887;hs3:36592398-36592398,hs11:77798132-77798132;hs3:36616060-36616060,hs3:151060362-151060362;hs3:36622680-36622680,hs11:20821041-20821041;hs3:36699240-36699240,hs3:167699741-167699741;hs3:36733331-36733331,hs11:107175723-107175723;hs3:36753185-36753185,hs3:97244841-97244841;hs3:36756810-36756810,hs3:55489182-55489182;hs3:36765775-36765775,hs11:61747385-61747385;hs3:36770478-36770478,hs3:47102844-47102844;hs3:36796399-36796399,hs3:146612686-146612686;hs3:36811314-36811314,hs3:111227231-111227231;hs3:36820981-36820981,hs3:194314407-194314407;hs3:37232851-37232851,hs3:194867081-194867081;hs3:37279578-37279578,hs3:181588760-181588760;hs3:37385772-37385772,hs11:66490473-66490473;hs3:37635835-37635835,hs11:17002832-17002832;hs3:37763525-37763525,hs3:47648679-47648679;hs3:37768557-37768557,hs11:16874057-16874057;hs3:37876710-37876710,hs11:58433292-58433292;hs3:37884080-37884080,hs3:174126918-174126918;hs3:37888689-37888689,hs3:133488772-133488772;hs3:37912552-37912552,hs3:141397109-141397109;hs3:37922661-37922661,hs11:133985412-133985412;hs3:37934565-37934565,hs11:58249125-58249125;hs3:38013480-38013480,hs3:82571386-82571386;hs3:38015563-38015563,hs11:100192317-100192317;hs3:38111890-38111890,hs3:185030980-185030980;hs3:38143407-38143407,hs3:171970424-171970424;hs3:38219682-38219682,hs11:21963959-21963959;hs3:38220434-38220434,hs3:179993786-179993786;hs3:38220434-38220434,hs3:179993787-179993787;hs3:38263966-38263966,hs11:17439313-17439313;hs3:38398408-38398408,hs3:145186852-145186852;hs3:38547366-38547366,hs3:120482174-120482174;hs3:38621178-38621178,hs3:52063872-52063872;hs3:38680073-38680073,hs3:193880069-193880069;hs3:38726975-38726975,hs3:148916286-148916286;hs3:38730203-38730203,hs3:76881345-76881345;hs3:38750533-38750533,hs11:79920909-79920909;hs3:38770621-38770621,hs3:74658462-74658462;hs3:38779500-38779500,hs11:88619797-88619797;hs3:38838047-38838047,hs11:77407114-77407114;hs3:38839240-38839240,hs11:9257199-9257199;hs3:38839240-38839240,hs11:9257200-9257200;hs3:38883230-38883230,hs3:190310985-190310985;hs3:38927663-38927663,hs11:124817289-124817289;hs3:38978377-38978377,hs11:82710384-82710384;hs3:38993165-38993165,hs3:53164871-53164871;hs3:38994251-38994251,hs11:125780322-125780322;hs3:39040833-39040833,hs3:134173614-134173614;hs3:39098606-39098606,hs11:117401208-117401208;hs3:39181452-39181452,hs3:89095356-89095356;hs3:39207261-39207261,hs11:23010503-23010503;hs3:39395837-39395837,hs21:10717469-10717469;hs3:39401703-39401703,hs11:81831696-81831696;hs3:39403288-39403288,hs11:41285409-41285409;hs3:39454798-39454798,hs3:65944719-65944719;hs3:39474867-39474867,hs3:169610120-169610120;hs3:39687892-39687892,hs3:85052695-85052695;hs3:39700829-39700829,hs11:90149945-90149945;hs3:39776039-39776039,hs11:45035439-45035439;hs3:39831438-39831438,hs11:41167956-41167956;hs3:39893905-39893905,hs11:127794214-127794214;hs3:39929428-39929428,hs3:184950332-184950332;hs3:39955384-39955384,hs11:15221389-15221389;hs3:40020956-40020956,hs3:134645677-134645677;hs3:40024745-40024745,hs11:66286833-66286833;hs3:40050801-40050801,hs11:102906083-102906083;hs3:40112279-40112279,hs11:117363202-117363202;hs3:40212672-40212672,hs3:166529814-166529814;hs3:40230687-40230687,hs11:102180770-102180770;hs3:40258007-40258007,hs3:69237076-69237076;hs3:40276214-40276214,hs11:83144906-83144906;hs3:40319042-40319042,hs11:127508772-127508772;hs3:40357588-40357588,hs3:132146161-132146161;hs3:40417607-40417607,hs11:15429154-15429154;hs3:40452819-40452819,hs3:41229027-41229027;hs3:40495411-40495411,hs3:151275574-151275574;hs3:40502584-40502584,hs3:49974188-49974188;hs3:40571453-40571453,hs3:127236316-127236316;hs3:40732965-40732965,hs11:80477502-80477502;hs3:40734732-40734732,hs3:101915130-101915130;hs3:40856720-40856720,hs3:42502861-42502861;hs3:40928245-40928245,hs3:55185471-55185471;hs3:40957062-40957062,hs11:118940339-118940339;hs3:40959724-40959724,hs11:89116340-89116340;hs3:40965515-40965515,hs11:56988952-56988952;hs3:41046766-41046766,hs3:57557540-57557540;hs3:41050984-41050984,hs3:73666767-73666767;hs3:41218557-41218557,hs3:49652775-49652775;hs3:41223452-41223452,hs3:51469821-51469821;hs3:41294553-41294553,hs11:28027423-28027423;hs3:41299785-41299785,hs11:47133817-47133817;hs3:41329273-41329273,hs11:107394194-107394194;hs3:41389827-41389827,hs3:120393909-120393909;hs3:41404784-41404784,hs3:197680218-197680218;hs3:41446270-41446270,hs3:145191160-145191160;hs3:41495335-41495335,hs3:52322473-52322473;hs3:41586091-41586091,hs3:187393748-187393748;hs3:41665146-41665146,hs3:102083287-102083287;hs3:41690064-41690064,hs3:158638719-158638719;hs3:41788821-41788821,hs3:164251134-164251134;hs3:41798773-41798773,hs3:94381960-94381960;hs3:41809204-41809204,hs11:68911245-68911245;hs3:41817958-41817958,hs11:116893432-116893432;hs3:41849969-41849969,hs3:196756746-196756746;hs3:41890464-41890464,hs3:44377397-44377397;hs3:41900637-41900637,hs3:84660156-84660156;hs3:41909168-41909168,hs11:102895445-102895445;hs3:41969968-41969968,hs11:108114366-108114366;hs3:42035775-42035775,hs11:104897808-104897808;hs3:42159737-42159737,hs11:77749338-77749338;hs3:42348493-42348493,hs3:54294568-54294568;hs3:42351877-42351877,hs11:34228514-34228514;hs3:42415694-42415694,hs3:181751115-181751115;hs3:42418440-42418440,hs11:80858255-80858255;hs3:42431391-42431391,hs3:70295573-70295573;hs3:42459881-42459881,hs3:115499964-115499964;hs3:42575414-42575414,hs11:109282380-109282380;hs3:42609644-42609644,hs3:93792174-93792174;hs3:42621455-42621455,hs3:190024962-190024962;hs3:42636029-42636029,hs11:78617597-78617597;hs3:42646689-42646689,hs11:78744362-78744362;hs3:42670795-42670795,hs11:42714174-42714174;hs3:42856391-42856391,hs3:110100671-110100671;hs3:42864179-42864179,hs11:64886113-64886113;hs3:43051943-43051943,hs3:140555473-140555473;hs3:43094196-43094196,hs3:154080532-154080532;hs3:43192878-43192878,hs3:161945081-161945081;hs3:43312041-43312041,hs3:105234009-105234009;hs3:43325873-43325873,hs11:79456759-79456759;hs3:43402384-43402384,hs3:52932087-52932087;hs3:43431267-43431267,hs11:104963377-104963377;hs3:43445480-43445480,hs11:14634756-14634756;hs3:43472655-43472655,hs11:12468179-12468179;hs3:43523679-43523679,hs11:97878362-97878362;hs3:43544729-43544729,hs3:137287273-137287273;hs3:43554246-43554246,hs3:147111782-147111782;hs3:43585152-43585152,hs11:38936538-38936538;hs3:43595211-43595211,hs11:12636943-12636943;hs3:43658580-43658580,hs11:60736534-60736534;hs3:43661748-43661748,hs11:29682223-29682223;hs3:43668064-43668064,hs11:115104860-115104860;hs3:43672101-43672101,hs11:114601102-114601102;hs3:43675861-43675861,hs11:30137354-30137354;hs3:43717338-43717338,hs11:106418326-106418326;hs3:43742345-43742345,hs11:6652743-6652743;hs3:43750695-43750695,hs11:16222944-16222944;hs3:43784636-43784636,hs11:125569407-125569407;hs3:43856624-43856624,hs11:2326785-2326785;hs3:44110845-44110845,hs11:126401868-126401868;hs3:44131588-44131588,hs3:101427775-101427775;hs3:44141777-44141777,hs3:158782899-158782899;hs3:44197533-44197533,hs3:167337232-167337232;hs3:44199717-44199717,hs11:7687285-7687285;hs3:44316292-44316292,hs3:163591272-163591272;hs3:44322374-44322374,hs3:63980004-63980004;hs3:44371059-44371059,hs11:38138511-38138511;hs3:44394683-44394683,hs3:74862851-74862851;hs3:44430290-44430290,hs3:97239274-97239274;hs3:44481439-44481439,hs3:66275905-66275905;hs3:44502228-44502228,hs3:157233643-157233643;hs3:44506609-44506609,hs4:49610128-49610128;hs3:44514194-44514194,hs11:62932352-62932352;hs3:44561433-44561433,hs3:55235118-55235118;hs3:44564871-44564871,hs3:167026119-167026119;hs3:44640083-44640083,hs11:46574535-46574535;hs3:44664497-44664497,hs11:33348725-33348725;hs3:44688564-44688564,hs11:95595557-95595557;hs3:44703539-44703539,hs11:114654970-114654970;hs3:44769561-44769561,hs3:82623205-82623205;hs3:44775472-44775472,hs3:167841083-167841083;hs3:44781163-44781163,hs3:53820936-53820936;hs3:44905418-44905418,hs3:45850381-45850381;hs3:44915575-44915575,hs3:179829036-179829036;hs3:44927229-44927229,hs3:186156771-186156771;hs3:45041110-45041110,hs3:114081570-114081570;hs3:45079953-45079953,hs11:128613156-128613156;hs3:45119809-45119809,hs3:167877928-167877928;hs3:45132103-45132103,hs3:178445162-178445162;hs3:45149986-45149986,hs3:150788156-150788156;hs3:45166524-45166524,hs3:74578291-74578291;hs3:45220422-45220422,hs11:9111157-9111157;hs3:45229077-45229077,hs3:134433569-134433569;hs3:45239923-45239923,hs3:109948555-109948555;hs3:45259779-45259779,hs11:59906030-59906030;hs3:45268955-45268955,hs3:136545594-136545594;hs3:45284409-45284409,hs3:133143186-133143186;hs3:45388734-45388734,hs3:196417015-196417015;hs3:45472676-45472676,hs3:184953895-184953895;hs3:45503733-45503733,hs11:45500220-45500220;hs3:45559093-45559093,hs3:187649150-187649150;hs3:45654378-45654378,hs3:186899869-186899869;hs3:45682016-45682016,hs11:65368391-65368391;hs3:45691143-45691143,hs3:189567090-189567090;hs3:45721991-45721991,hs3:141502434-141502434;hs3:45750404-45750404,hs11:131903048-131903048;hs3:45879627-45879627,hs11:106547598-106547598;hs3:45890681-45890681,hs3:75461768-75461768;hs3:46058632-46058632,hs11:84703863-84703863;hs3:46062614-46062614,hs3:167238819-167238819;hs3:46067362-46067362,hs3:86565387-86565387;hs3:46083539-46083539,hs3:53517885-53517885;hs3:46088389-46088389,hs3:108791335-108791335;hs3:46122305-46122305,hs3:137124408-137124408;hs3:46153834-46153834,hs3:98807511-98807511;hs3:46371723-46371723,hs11:105452338-105452338;hs3:46464055-46464055,hs3:112308348-112308348;hs3:46492232-46492232,hs11:106255474-106255474;hs3:46496288-46496288,hs3:82860531-82860531;hs3:46514929-46514929,hs11:79966500-79966500;hs3:46519180-46519180,hs11:46428695-46428695;hs3:46614993-46614993,hs11:24342895-24342895;hs3:46618008-46618008,hs11:98147814-98147814;hs3:46678422-46678422,hs3:193097975-193097975;hs3:46681045-46681045,hs11:19718133-19718133;hs3:46712733-46712733,hs3:82781015-82781015;hs3:46714740-46714740,hs3:53976425-53976425;hs3:46831338-46831338,hs11:96632356-96632356;hs3:46846594-46846594,hs21:11153074-11153074;hs3:46846618-46846618,hs3:149311201-149311201;hs3:46887104-46887104,hs11:118831534-118831534;hs3:46895572-46895572,hs11:92108570-92108570;hs3:46898633-46898633,hs11:116426107-116426107;hs3:46919778-46919778,hs11:78793094-78793094;hs3:46939227-46939227,hs3:82548134-82548134;hs3:46941561-46941561,hs3:50648678-50648678;hs3:46981484-46981484,hs11:98777753-98777753;hs3:46989161-46989161,hs3:104884244-104884244;hs3:47018907-47018907,hs3:184511021-184511021;hs3:47043576-47043576,hs11:126474983-126474983;hs3:47063863-47063863,hs11:85592948-85592948;hs3:47082869-47082869,hs3:84664476-84664476;hs3:47113769-47113769,hs3:134614334-134614334;hs3:47246415-47246415,hs3:78770801-78770801;hs3:47284695-47284695,hs11:115340678-115340678;hs3:47293356-47293356,hs3:124724799-124724799;hs3:47362143-47362143,hs3:61422490-61422490;hs3:47366321-47366321,hs11:61669518-61669518;hs3:47373967-47373967,hs3:80802640-80802640;hs3:47390022-47390022,hs3:164105534-164105534;hs3:47508932-47508932,hs11:25472989-25472989;hs3:47516006-47516006,hs11:82955546-82955546;hs3:47591403-47591403,hs3:87819420-87819420;hs3:47607006-47607006,hs3:99687187-99687187;hs3:47676433-47676433,hs11:18302009-18302009;hs3:47814801-47814801,hs3:82978782-82978782;hs3:47842676-47842676,hs11:23154330-23154330;hs3:47874552-47874552,hs3:188261297-188261297;hs3:48006165-48006165,hs11:50556354-50556354;hs3:48039769-48039769,hs3:109089677-109089677;hs3:48082763-48082763,hs3:95985996-95985996;hs3:48091377-48091377,hs11:134053468-134053468;hs3:48191563-48191563,hs3:48308528-48308528;hs3:48257234-48257234,hs11:41077393-41077393;hs3:48361801-48361801,hs11:5245750-5245750;hs3:48430483-48430483,hs11:66391565-66391565;hs3:48441263-48441263,hs3:74998653-74998653;hs3:48442631-48442631,hs3:190591533-190591533;hs3:48451043-48451043,hs3:65355887-65355887;hs3:48650317-48650317,hs3:84259872-84259872;hs3:48687533-48687533,hs11:17068253-17068253;hs3:48691485-48691485,hs11:98754002-98754002;hs3:48784305-48784305,hs3:123802233-123802233;hs3:48808863-48808863,hs3:48809901-48809901;hs3:48808773-48808773,hs11:80554197-80554197;hs3:48824546-48824546,hs3:98381949-98381949;hs3:48913042-48913042,hs3:176634048-176634048;hs3:48914232-48914232,hs3:190988079-190988079;hs3:48970881-48970881,hs3:116016193-116016193;hs3:49029386-49029386,hs11:1050014-1050014;hs3:49032320-49032320,hs3:86239796-86239796;hs3:49043996-49043996,hs3:167330259-167330259;hs3:49142264-49142264,hs3:181807793-181807793;hs3:49147263-49147263,hs3:112581899-112581899;hs3:49152335-49152335,hs3:157211935-157211935;hs3:49161526-49161526,hs11:17266134-17266134;hs3:49212087-49212087,hs11:90411043-90411043;hs3:49217654-49217654,hs11:96725099-96725099;hs3:49231453-49231453,hs3:161345603-161345603;hs3:49236112-49236112,hs3:81077798-81077798;hs3:49291398-49291398,hs11:57982482-57982482;hs3:49368109-49368109,hs3:162346553-162346553;hs3:49416920-49416920,hs3:100900064-100900064;hs3:49420965-49420965,hs3:151586771-151586771;hs3:49443828-49443828,hs11:107988570-107988570;hs3:49465488-49465488,hs3:192267867-192267867;hs3:49470962-49470962,hs11:80063042-80063042;hs3:49485953-49485953,hs3:183605780-183605780;hs3:49487507-49487507,hs3:55494420-55494420;hs3:49565816-49565816,hs11:16128959-16128959;hs3:49593270-49593270,hs3:142810653-142810653;hs3:49601706-49601706,hs3:186143511-186143511;hs3:49636988-49636988,hs3:102604660-102604660;hs3:49695344-49695344,hs11:24486882-24486882;hs3:49786416-49786416,hs11:21653069-21653069;hs3:49890583-49890583,hs3:70670806-70670806;hs3:49895424-49895424,hs11:124424502-124424502;hs3:49907172-49907172,hs3:128135397-128135397;hs3:49922460-49922460,hs3:192354794-192354794;hs3:49952370-49952370,hs3:132846044-132846044;hs3:50005144-50005144,hs3:109337595-109337595;hs3:50007850-50007850,hs3:160635028-160635028;hs3:50012140-50012140,hs11:120667680-120667680;hs3:50015536-50015536,hs11:113800328-113800328;hs3:50069718-50069718,hs3:173254959-173254959;hs3:50076812-50076812,hs3:114430108-114430108;hs3:50128235-50128235,hs3:169273623-169273623;hs3:50180533-50180533,hs3:158408023-158408023;hs3:50185517-50185517,hs11:34675039-34675039;hs3:50199952-50199952,hs11:68983358-68983358;hs3:50203745-50203745,hs11:116116168-116116168;hs3:50246191-50246191,hs11:131114241-131114241;hs3:50278947-50278947,hs11:12816950-12816950;hs3:50339285-50339285,hs11:3154189-3154189;hs3:50343234-50343234,hs11:33356985-33356985;hs3:50387718-50387718,hs11:17873548-17873548;hs3:50419314-50419314,hs3:175770149-175770149;hs3:50452815-50452815,hs3:85329128-85329128;hs3:50471260-50471260,hs3:191052630-191052630;hs3:50505141-50505141,hs3:161717805-161717805;hs3:50522002-50522002,hs3:145375326-145375326;hs3:50522869-50522869,hs11:83927492-83927492;hs3:50522868-50522868,hs11:83927492-83927492;hs3:50649076-50649076,hs3:194774634-194774634;hs3:50709060-50709060,hs3:104714706-104714706;hs3:50711950-50711950,hs3:160287088-160287088;hs3:50722279-50722279,hs3:81262104-81262104;hs3:50751981-50751981,hs11:10221747-10221747;hs3:50768296-50768296,hs3:123862071-123862071;hs3:50790263-50790263,hs11:114955229-114955229;hs3:50822650-50822650,hs3:106462431-106462431;hs3:50832614-50832614,hs3:105156108-105156108;hs3:50879042-50879042,hs11:94230401-94230401;hs3:51039624-51039624,hs3:72889612-72889612;hs3:51070440-51070440,hs11:111192695-111192695;hs3:51094176-51094176,hs11:131218396-131218396;hs3:51154058-51154058,hs11:115808443-115808443;hs3:51157986-51157986,hs11:121709494-121709494;hs3:51180409-51180409,hs3:107595179-107595179;hs3:51213056-51213056,hs3:181685118-181685118;hs3:51269532-51269532,hs11:131194933-131194933;hs3:51275755-51275755,hs3:148025483-148025483;hs3:51293174-51293174,hs11:25458460-25458460;hs3:51333221-51333221,hs3:127635150-127635150;hs3:51343428-51343428,hs3:130950258-130950258;hs3:51400045-51400045,hs3:164178657-164178657;hs3:51455581-51455581,hs11:6259574-6259574;hs3:51486414-51486414,hs11:132968920-132968920;hs3:51514484-51514484,hs3:74640571-74640571;hs3:51596771-51596771,hs3:167329765-167329765;hs3:51625586-51625586,hs3:121664493-121664493;hs3:51637722-51637722,hs3:115290111-115290111;hs3:51735753-51735753,hs3:99693372-99693372;hs3:51909340-51909340,hs3:160346073-160346073;hs3:51911492-51911492,hs3:126617774-126617774;hs3:51920359-51920359,hs3:172079897-172079897;hs3:51921364-51921364,hs11:134941772-134941772;hs3:51972593-51972593,hs11:17114921-17114921;hs3:52067832-52067832,hs11:64468533-64468533;hs3:52193432-52193432,hs11:56418898-56418898;hs3:52211670-52211670,hs11:122899437-122899437;hs3:52255540-52255540,hs11:124486187-124486187;hs3:52315571-52315571,hs3:190193509-190193509;hs3:52380461-52380461,hs3:159291986-159291986;hs3:52413870-52413870,hs3:122501736-122501736;hs3:52418359-52418359,hs3:170354348-170354348;hs3:52490694-52490694,hs11:43846035-43846035;hs3:52506777-52506777,hs3:155530992-155530992;hs3:52525582-52525582,hs11:33587135-33587135;hs3:52548313-52548313,hs11:62211755-62211755;hs3:52554974-52554974,hs11:64446565-64446565;hs3:52562494-52562494,hs11:122336650-122336650;hs3:52582421-52582421,hs11:103431172-103431172;hs3:52582420-52582420,hs11:103431173-103431173;hs3:52608830-52608830,hs3:192203680-192203680;hs3:52614672-52614672,hs3:101432386-101432386;hs3:52618676-52618676,hs3:141051143-141051143;hs3:52635160-52635160,hs11:134706733-134706733;hs3:52647899-52647899,hs11:94189946-94189946;hs3:52753474-52753474,hs11:1069978-1069978;hs3:52796053-52796053,hs3:126381259-126381259;hs3:52868326-52868326,hs3:139604252-139604252;hs3:52873847-52873847,hs3:96942373-96942373;hs3:52890128-52890128,hs11:26658184-26658184;hs3:52927451-52927451,hs11:115305987-115305987;hs3:52973468-52973468,hs3:54237332-54237332;hs3:53028488-53028488,hs3:106617285-106617285;hs3:53043701-53043701,hs11:919145-919145;hs3:53127530-53127530,hs3:62624847-62624847;hs3:53187509-53187509,hs11:102978745-102978745;hs3:53297572-53297572,hs11:28399125-28399125;hs3:53298433-53298433,hs3:110940627-110940627;hs3:53298434-53298434,hs3:110940627-110940627;hs3:53309488-53309488,hs11:127786544-127786544;hs3:53429613-53429613,hs11:22943810-22943810;hs3:53433660-53433660,hs11:9897739-9897739;hs3:53515138-53515138,hs3:186175056-186175056;hs3:53551491-53551491,hs11:111486392-111486392;hs3:53561740-53561740,hs11:13702509-13702509;hs3:53565643-53565643,hs3:58845275-58845275;hs3:53622270-53622270,hs11:38867149-38867149;hs3:53640867-53640867,hs3:96658587-96658587;hs3:53692678-53692678,hs11:128494046-128494046;hs3:53692678-53692678,hs3:88863995-88863995;hs3:53693254-53693254,hs3:192227599-192227599;hs3:53718635-53718635,hs11:107370975-107370975;hs3:53843629-53843629,hs11:16714064-16714064;hs3:53851723-53851723,hs3:152156608-152156608;hs3:53958336-53958336,hs3:138306543-138306543;hs3:54047861-54047861,hs3:142248715-142248715;hs3:54089634-54089634,hs3:69093377-69093377;hs3:54093685-54093685,hs3:84596977-84596977;hs3:54121072-54121072,hs3:143689588-143689588;hs3:54139044-54139044,hs3:119605599-119605599;hs3:54155610-54155610,hs11:115614632-115614632;hs3:54156134-54156134,hs11:45901814-45901814;hs3:54166768-54166768,hs3:151948111-151948111;hs3:54177697-54177697,hs11:102807165-102807165;hs3:54248635-54248635,hs3:127869758-127869758;hs3:54309945-54309945,hs11:106870044-106870044;hs3:54481665-54481665,hs11:128480181-128480181;hs3:54515360-54515360,hs3:121772963-121772963;hs3:54565158-54565158,hs3:67685149-67685149;hs3:54758549-54758549,hs3:105257343-105257343;hs3:54857122-54857122,hs11:124724131-124724131;hs3:54874835-54874835,hs3:189172043-189172043;hs3:54941994-54941994,hs11:56305918-56305918;hs3:55278666-55278666,hs3:182908558-182908558;hs3:55368103-55368103,hs3:159093603-159093603;hs3:55505671-55505671,hs3:138103779-138103779;hs3:55723742-55723742,hs3:186878951-186878951;hs3:55732471-55732471,hs11:2609724-2609724;hs3:55747348-55747348,hs3:63994324-63994324;hs3:55753258-55753258,hs11:3722320-3722320;hs3:55758407-55758407,hs3:108004709-108004709;hs3:55853019-55853019,hs3:171333565-171333565;hs3:55878723-55878723,hs3:59125763-59125763;hs3:56048685-56048685,hs11:48190141-48190141;hs3:56102482-56102482,hs11:95147440-95147440;hs3:56107832-56107832,hs3:190613876-190613876;hs3:56131321-56131321,hs11:106772704-106772704;hs3:56191050-56191050,hs11:92482442-92482442;hs3:56224383-56224383,hs11:13374947-13374947;hs3:56349344-56349344,hs11:98482234-98482234;hs3:56396968-56396968,hs3:65628215-65628215;hs3:56437205-56437205,hs11:97829997-97829997;hs3:56439951-56439951,hs3:111767882-111767882;hs3:56461486-56461486,hs11:43838045-43838045;hs3:56466453-56466453,hs3:169166217-169166217;hs3:56480805-56480805,hs3:157795928-157795928;hs3:56485588-56485588,hs11:102845316-102845316;hs3:56498731-56498731,hs3:137958814-137958814;hs3:56609090-56609090,hs3:100178565-100178565;hs3:56720953-56720953,hs3:116113712-116113712;hs3:56742810-56742810,hs3:87079812-87079812;hs3:56743677-56743677,hs3:146665121-146665121;hs3:56750684-56750684,hs11:131120296-131120296;hs3:56766745-56766745,hs3:73874245-73874245;hs3:56784877-56784877,hs3:133513728-133513728;hs3:56932173-56932173,hs3:142420424-142420424;hs3:56961509-56961509,hs3:82439854-82439854;hs3:56968308-56968308,hs11:62475438-62475438;hs3:56992206-56992206,hs3:141805284-141805284;hs3:57003955-57003955,hs3:115235683-115235683;hs3:57077291-57077291,hs11:39497329-39497329;hs3:57083439-57083439,hs3:63931068-63931068;hs3:57095382-57095382,hs11:120331692-120331692;hs3:57096349-57096349,hs3:180028769-180028769;hs3:57100904-57100904,hs3:104801094-104801094;hs3:57148540-57148540,hs11:19985679-19985679;hs3:57181355-57181355,hs3:193109691-193109691;hs3:57241858-57241858,hs11:27038842-27038842;hs3:57256433-57256433,hs3:122960418-122960418;hs3:57274201-57274201,hs3:184371698-184371698;hs3:57288848-57288848,hs11:117359217-117359217;hs3:57322670-57322670,hs3:124986151-124986151;hs3:57341489-57341489,hs11:45413882-45413882;hs3:57342651-57342651,hs3:182937362-182937362;hs3:57351438-57351438,hs11:124165494-124165494;hs3:57388277-57388277,hs11:132483478-132483478;hs3:57389181-57389181,hs3:87805987-87805987;hs3:57401365-57401365,hs3:172837257-172837257;hs3:57550100-57550100,hs11:7653884-7653884;hs3:57609436-57609436,hs3:74434090-74434090;hs3:57619528-57619528,hs3:120345072-120345072;hs3:57679185-57679185,hs3:148847505-148847505;hs3:57679186-57679186,hs3:148847506-148847506;hs3:57708110-57708110,hs3:137350616-137350616;hs3:57732400-57732400,hs11:121331909-121331909;hs3:57735138-57735138,hs11:113157536-113157536;hs3:57777568-57777568,hs3:74200515-74200515;hs3:57806457-57806457,hs3:164185236-164185236;hs3:57811415-57811415,hs11:17041549-17041549;hs3:57840507-57840507,hs3:106359136-106359136;hs3:57865758-57865758,hs11:94653930-94653930;hs3:57922674-57922674,hs3:77593049-77593049;hs3:57922972-57922972,hs3:80016396-80016396;hs3:57936037-57936037,hs3:193101721-193101721;hs3:58041111-58041111,hs3:104331842-104331842;hs3:58050808-58050808,hs11:61667467-61667467;hs3:58071440-58071440,hs3:72392279-72392279;hs3:58115874-58115874,hs11:95712752-95712752;hs3:58178169-58178169,hs3:134576463-134576463;hs3:58198564-58198564,hs21:11152163-11152163;hs3:58244814-58244814,hs3:116166496-116166496;hs3:58389356-58389356,hs11:83449811-83449811;hs3:58418679-58418679,hs3:123113171-123113171;hs3:58457485-58457485,hs3:99275967-99275967;hs3:58458099-58458099,hs11:67134579-67134579;hs3:58464564-58464564,hs11:348384-348384;hs3:58597947-58597947,hs3:100943663-100943663;hs3:58637846-58637846,hs11:36736594-36736594;hs3:58652054-58652054,hs3:140794122-140794122;hs3:58691483-58691483,hs11:6313355-6313355;hs3:58748934-58748934,hs3:98508227-98508227;hs3:58802183-58802183,hs3:113796818-113796818;hs3:58827680-58827680,hs3:74752809-74752809;hs3:58857283-58857283,hs3:126369587-126369587;hs3:58886666-58886666,hs11:28383859-28383859;hs3:58915859-58915859,hs3:158987431-158987431;hs3:59057228-59057228,hs11:37933275-37933275;hs3:59110934-59110934,hs11:119192306-119192306;hs3:59189261-59189261,hs3:130201085-130201085;hs3:59194633-59194633,hs3:132824539-132824539;hs3:59197823-59197823,hs11:4691228-4691228;hs3:59225571-59225571,hs3:63115576-63115576;hs3:59238005-59238005,hs3:159450945-159450945;hs3:59240695-59240695,hs11:44105609-44105609;hs3:59253722-59253722,hs3:75528334-75528334;hs3:59295997-59295997,hs3:149279405-149279405;hs3:59509946-59509946,hs3:104258396-104258396;hs3:59569036-59569036,hs11:103885908-103885908;hs3:59580337-59580337,hs3:148298585-148298585;hs3:59677995-59677995,hs3:177636324-177636324;hs3:59718235-59718235,hs3:106156530-106156530;hs3:59971618-59971618,hs3:85119160-85119160;hs3:60002455-60002455,hs3:152768462-152768462;hs3:60104211-60104211,hs3:173038504-173038504;hs3:60177406-60177406,hs3:142580304-142580304;hs3:60184878-60184878,hs11:14834667-14834667;hs3:60237045-60237045,hs11:133768361-133768361;hs3:60303366-60303366,hs11:16408587-16408587;hs3:60308197-60308197,hs11:30858034-30858034;hs3:60350646-60350646,hs11:55305734-55305734;hs3:60651030-60651030,hs3:187561327-187561327;hs3:60658191-60658191,hs11:106295993-106295993;hs3:60697610-60697610,hs3:67913940-67913940;hs3:60746553-60746553,hs3:94708823-94708823;hs3:60751434-60751434,hs11:66556558-66556558;hs3:60756662-60756662,hs11:3812384-3812384;hs3:60855464-60855464,hs11:111045690-111045690;hs3:60859986-60859986,hs3:87754314-87754314;hs3:60992213-60992213,hs11:11087243-11087243;hs3:61150237-61150237,hs11:129874936-129874936;hs3:61192555-61192555,hs3:108288825-108288825;hs3:61245452-61245452,hs11:106058980-106058980;hs3:61258030-61258030,hs11:3830841-3830841;hs3:61259380-61259380,hs3:188573854-188573854;hs3:61340546-61340546,hs11:114992113-114992113;hs3:61365941-61365941,hs11:15534745-15534745;hs3:61368548-61368548,hs11:107029152-107029152;hs3:61379436-61379436,hs3:173784510-173784510;hs3:61410861-61410861,hs11:77084631-77084631;hs3:61412681-61412681,hs3:159357497-159357497;hs3:61583749-61583749,hs11:134288351-134288351;hs3:61611010-61611010,hs3:130651686-130651686;hs3:61668467-61668467,hs11:8668048-8668048;hs3:61679008-61679008,hs3:192474028-192474028;hs3:61685990-61685990,hs3:179644228-179644228;hs3:61737030-61737030,hs11:86229765-86229765;hs3:61842707-61842707,hs3:79412303-79412303;hs3:61873301-61873301,hs3:138141294-138141294;hs3:61939439-61939439,hs3:80318396-80318396;hs3:62058848-62058848,hs11:105749060-105749060;hs3:62119936-62119936,hs3:80725194-80725194;hs3:62196360-62196360,hs3:146883758-146883758;hs3:62213631-62213631,hs3:132832130-132832130;hs3:62261699-62261699,hs3:68781105-68781105;hs3:62329932-62329932,hs3:181880350-181880350;hs3:62442508-62442508,hs11:131957180-131957180;hs3:62560558-62560558,hs11:96572055-96572055;hs3:62587586-62587586,hs11:98470985-98470985;hs3:62597796-62597796,hs3:186973509-186973509;hs3:62862414-62862414,hs3:160313143-160313143;hs3:62882950-62882950,hs11:19894789-19894789;hs3:62897751-62897751,hs3:73683114-73683114;hs3:62965321-62965321,hs3:192198779-192198779;hs3:63075587-63075587,hs11:65061817-65061817;hs3:63116676-63116676,hs3:141347302-141347302;hs3:63424678-63424678,hs3:195148400-195148400;hs3:63431269-63431269,hs3:168700476-168700476;hs3:63547146-63547146,hs11:105894638-105894638;hs3:63553229-63553229,hs11:118213984-118213984;hs3:63692617-63692617,hs3:187280460-187280460;hs3:63703140-63703140,hs11:66241458-66241458;hs3:63747659-63747659,hs3:103358314-103358314;hs3:63881296-63881296,hs3:67006683-67006683;hs3:63935232-63935232,hs3:102929568-102929568;hs3:63935948-63935948,hs11:133665187-133665187;hs3:64032558-64032558,hs11:50702447-50702447;hs3:64098039-64098039,hs11:108953201-108953201;hs3:64148563-64148563,hs3:185834364-185834364;hs3:64156982-64156982,hs3:132795494-132795494;hs3:64170652-64170652,hs11:9657235-9657235;hs3:64211204-64211204,hs3:109821039-109821039;hs3:64279338-64279338,hs11:67059892-67059892;hs3:64307916-64307916,hs3:108902155-108902155;hs3:64417405-64417405,hs3:140441147-140441147;hs3:64484483-64484483,hs11:119364240-119364240;hs3:64624463-64624463,hs11:64551305-64551305;hs3:64625776-64625776,hs11:84722737-84722737;hs3:64703452-64703452,hs3:82337464-82337464;hs3:64706506-64706506,hs3:177538748-177538748;hs3:64777736-64777736,hs3:99785074-99785074;hs3:64778821-64778821,hs3:188910108-188910108;hs3:64789202-64789202,hs3:188744779-188744779;hs3:64794524-64794524,hs11:92239681-92239681;hs3:65104105-65104105,hs3:120358553-120358553;hs3:65206513-65206513,hs11:14864420-14864420;hs3:65280122-65280122,hs3:80274263-80274263;hs3:65367890-65367890,hs11:126006824-126006824;hs3:65429286-65429286,hs11:3383459-3383459;hs3:65549383-65549383,hs11:41925150-41925150;hs3:65557574-65557574,hs11:90705172-90705172;hs3:65666800-65666800,hs3:123298852-123298852;hs3:65730864-65730864,hs21:10976300-10976300;hs3:65932791-65932791,hs3:170051363-170051363;hs3:66376479-66376479,hs11:25052221-25052221;hs3:66409981-66409981,hs3:84563014-84563014;hs3:66632694-66632694,hs11:104834220-104834220;hs3:66636192-66636192,hs3:193787656-193787656;hs3:66645069-66645069,hs11:4014401-4014401;hs3:66656667-66656667,hs11:65532663-65532663;hs3:66733056-66733056,hs3:104059367-104059367;hs3:66775676-66775676,hs3:150545760-150545760;hs3:66867408-66867408,hs3:139086424-139086424;hs3:66881546-66881546,hs3:144560256-144560256;hs3:66887188-66887188,hs11:5712206-5712206;hs3:66890751-66890751,hs11:85662643-85662643;hs3:66893744-66893744,hs3:181216080-181216080;hs3:66983364-66983364,hs3:189202230-189202230;hs3:67019792-67019792,hs11:78146406-78146406;hs3:67020759-67020759,hs3:145878853-145878853;hs3:67097595-67097595,hs3:69325884-69325884;hs3:67114974-67114974,hs3:135098448-135098448;hs3:67193832-67193832,hs3:154147216-154147216;hs3:67224381-67224381,hs11:83874620-83874620;hs3:67230409-67230409,hs3:102083105-102083105;hs3:67247664-67247664,hs11:134717112-134717112;hs3:67486774-67486774,hs11:57596806-57596806;hs3:67528879-67528879,hs11:27752682-27752682;hs3:67535841-67535841,hs11:93996986-93996986;hs3:67553696-67553696,hs11:30443219-30443219;hs3:67557971-67557971,hs11:7687817-7687817;hs3:67564997-67564997,hs3:193191984-193191984;hs3:67586284-67586284,hs3:95097711-95097711;hs3:67593052-67593052,hs11:125324533-125324533;hs3:67616719-67616719,hs3:175559687-175559687;hs3:67693750-67693750,hs3:195033996-195033996;hs3:67735746-67735746,hs3:111195672-111195672;hs3:67746036-67746036,hs11:42624415-42624415;hs3:67809775-67809775,hs3:129221747-129221747;hs3:67823355-67823355,hs11:110156500-110156500;hs3:68003787-68003787,hs11:128029781-128029781;hs3:68006455-68006455,hs3:109877377-109877377;hs3:68014098-68014098,hs11:132208427-132208427;hs3:68020509-68020509,hs11:39385069-39385069;hs3:68099839-68099839,hs11:83681412-83681412;hs3:68116257-68116257,hs3:95005440-95005440;hs3:68147082-68147082,hs11:125570109-125570109;hs3:68178612-68178612,hs11:132883367-132883367;hs3:68190691-68190691,hs3:166430397-166430397;hs3:68238204-68238204,hs3:124294167-124294167;hs3:68244578-68244578,hs11:37451914-37451914;hs3:68390102-68390102,hs11:92891464-92891464;hs3:68422136-68422136,hs11:101775985-101775985;hs3:68449368-68449368,hs11:68562166-68562166;hs3:68482812-68482812,hs11:131145446-131145446;hs3:68619789-68619789,hs11:131567684-131567684;hs3:68620014-68620014,hs11:3848969-3848969;hs3:68620014-68620014,hs11:3848968-3848968;hs3:68667262-68667262,hs11:80890380-80890380;hs3:68715509-68715509,hs11:56050612-56050612;hs3:68726275-68726275,hs3:153673978-153673978;hs3:68777819-68777819,hs3:78934866-78934866;hs3:68779219-68779219,hs3:150611917-150611917;hs3:68867839-68867839,hs11:125397863-125397863;hs3:68947330-68947330,hs11:15374150-15374150;hs3:69103637-69103637,hs11:118779751-118779751;hs3:69142986-69142986,hs11:18061136-18061136;hs3:69151549-69151549,hs11:93027932-93027932;hs3:69158358-69158358,hs3:112462063-112462063;hs3:69213214-69213214,hs11:7460734-7460734;hs3:69221696-69221696,hs3:123384003-123384003;hs3:69249955-69249955,hs11:44084532-44084532;hs3:69319229-69319229,hs3:70756028-70756028;hs3:69400373-69400373,hs3:172300482-172300482;hs3:69418007-69418007,hs3:186177206-186177206;hs3:69457303-69457303,hs3:176617658-176617658;hs3:69510857-69510857,hs3:77047436-77047436;hs3:69863658-69863658,hs11:49585311-49585311;hs3:69880582-69880582,hs11:56123179-56123179;hs3:70278089-70278089,hs11:10466672-10466672;hs3:70303433-70303433,hs3:129102754-129102754;hs3:70305588-70305588,hs11:99561182-99561182;hs3:70485350-70485350,hs11:116770747-116770747;hs3:70689450-70689450,hs11:94559221-94559221;hs3:70695834-70695834,hs3:189992093-189992093;hs3:70812234-70812234,hs3:115244274-115244274;hs3:70842193-70842193,hs3:171325191-171325191;hs3:70884158-70884158,hs3:119780199-119780199;hs3:70900977-70900977,hs3:105312875-105312875;hs3:70916451-70916451,hs3:190864933-190864933;hs3:70948213-70948213,hs11:61468066-61468066;hs3:70993388-70993388,hs3:149273985-149273985;hs3:71059612-71059612,hs3:95874367-95874367;hs3:71235738-71235738,hs3:156671512-156671512;hs3:71261321-71261321,hs3:128388085-128388085;hs3:71347241-71347241,hs11:80601247-80601247;hs3:71362119-71362119,hs3:122481401-122481401;hs3:71368991-71368991,hs11:35882883-35882883;hs3:71567990-71567990,hs11:62254661-62254661;hs3:71619867-71619867,hs11:81137847-81137847;hs3:71625996-71625996,hs11:109645959-109645959;hs3:71784312-71784312,hs3:143806047-143806047;hs3:71862196-71862196,hs11:6692759-6692759;hs3:71888032-71888032,hs11:42685776-42685776;hs3:71902452-71902452,hs3:189302809-189302809;hs3:71932567-71932567,hs3:185303350-185303350;hs3:71932568-71932568,hs3:185303350-185303350;hs3:71937159-71937159,hs3:182676735-182676735;hs3:72007774-72007774,hs11:19841383-19841383;hs3:72060727-72060727,hs3:155893442-155893442;hs3:72125409-72125409,hs11:110524367-110524367;hs3:72147647-72147647,hs3:187477034-187477034;hs3:72152890-72152890,hs3:107769074-107769074;hs3:72219110-72219110,hs3:172216493-172216493;hs3:72238633-72238633,hs11:67286267-67286267;hs3:72252790-72252790,hs3:98298121-98298121;hs3:72259100-72259100,hs3:73971021-73971021;hs3:72274683-72274683,hs3:100669576-100669576;hs3:72355872-72355872,hs3:164510193-164510193;hs3:72394373-72394373,hs11:85368298-85368298;hs3:72470647-72470647,hs3:182233028-182233028;hs3:72645543-72645543,hs11:115859987-115859987;hs3:72694851-72694851,hs3:147191426-147191426;hs3:72715645-72715645,hs11:100760026-100760026;hs3:72864383-72864383,hs11:85070658-85070658;hs3:72882512-72882512,hs3:161113570-161113570;hs3:72899980-72899980,hs3:154046780-154046780;hs3:73020458-73020458,hs11:62923979-62923979;hs3:73041557-73041557,hs3:158812950-158812950;hs3:73113422-73113422,hs3:128661529-128661529;hs3:73115403-73115403,hs11:81929439-81929439;hs3:73141533-73141533,hs3:140827632-140827632;hs3:73285787-73285787,hs3:82804632-82804632;hs3:73452144-73452144,hs3:160693682-160693682;hs3:73502749-73502749,hs11:114562305-114562305;hs3:73506806-73506806,hs11:11329370-11329370;hs3:73608960-73608960,hs3:188204457-188204457;hs3:73659557-73659557,hs3:192842352-192842352;hs3:73723801-73723801,hs3:113709674-113709674;hs3:73731171-73731171,hs3:173598963-173598963;hs3:73760421-73760421,hs3:109960186-109960186;hs3:73782735-73782735,hs3:151294826-151294826;hs3:73790814-73790814,hs3:101619589-101619589;hs3:73891835-73891835,hs11:133964654-133964654;hs3:73898761-73898761,hs11:12409801-12409801;hs3:73966431-73966431,hs3:97979827-97979827;hs3:74007258-74007258,hs11:133784941-133784941;hs3:74012593-74012593,hs11:34345073-34345073;hs3:74088066-74088066,hs3:169243532-169243532;hs3:74093942-74093942,hs21:10554610-10554610;hs3:74187309-74187309,hs3:127555404-127555404;hs3:74193835-74193835,hs11:96052094-96052094;hs3:74225101-74225101,hs11:108443070-108443070;hs3:74454738-74454738,hs11:99349953-99349953;hs3:74494321-74494321,hs3:125460104-125460104;hs3:74516054-74516054,hs3:135600005-135600005;hs3:74603144-74603144,hs3:131462230-131462230;hs3:74614294-74614294,hs11:98995925-98995925;hs3:74672080-74672080,hs11:344384-344384;hs3:74683041-74683041,hs11:3686423-3686423;hs3:74726909-74726909,hs11:24101095-24101095;hs3:74729692-74729692,hs3:120604704-120604704;hs3:74738103-74738103,hs11:132121138-132121138;hs3:74849285-74849285,hs21:10433834-10433834;hs3:74855112-74855112,hs11:109391471-109391471;hs3:74861526-74861526,hs11:95178822-95178822;hs3:74906472-74906472,hs3:178571566-178571566;hs3:74990608-74990608,hs11:88604261-88604261;hs3:74998465-74998465,hs3:166425468-166425468;hs3:75001889-75001889,hs3:182271497-182271497;hs3:75014410-75014410,hs3:166405105-166405105;hs3:75071855-75071855,hs3:75841536-75841536;hs3:75073781-75073781,hs11:48186996-48186996;hs3:75135116-75135116,hs3:166290757-166290757;hs3:75148429-75148429,hs3:77343554-77343554;hs3:75182501-75182501,hs3:107087365-107087365;hs3:75424548-75424548,hs11:93833783-93833783;hs3:75453937-75453937,hs11:32991737-32991737;hs3:75464960-75464960,hs3:194783897-194783897;hs3:75468673-75468673,hs3:130901895-130901895;hs3:75846633-75846633,hs3:181461554-181461554;hs3:75914152-75914152,hs11:64991749-64991749;hs3:75958459-75958459,hs3:78755720-78755720;hs3:76017765-76017765,hs3:118548603-118548603;hs3:76078500-76078500,hs11:10286174-10286174;hs3:76130711-76130711,hs3:83725188-83725188;hs3:76342132-76342132,hs11:37659914-37659914;hs3:76581283-76581283,hs3:94007600-94007600;hs3:76690195-76690195,hs3:79469711-79469711;hs3:76691958-76691958,hs3:150760108-150760108;hs3:77060627-77060627,hs3:181078917-181078917;hs3:77063695-77063695,hs11:129809896-129809896;hs3:77084187-77084187,hs11:36906107-36906107;hs3:77138215-77138215,hs3:150330062-150330062;hs3:77331125-77331125,hs11:40089591-40089591;hs3:77364098-77364098,hs3:113792794-113792794;hs3:77419798-77419798,hs3:146731024-146731024;hs3:77485071-77485071,hs11:37333306-37333306;hs3:77567011-77567011,hs11:89127566-89127566;hs3:77567011-77567011,hs11:49335382-49335382;hs3:77614649-77614649,hs11:61566940-61566940;hs3:77692776-77692776,hs11:27754850-27754850;hs3:77836810-77836810,hs3:110264286-110264286;hs3:77893138-77893138,hs3:97819329-97819329;hs3:77901291-77901291,hs11:121218855-121218855;hs3:77952183-77952183,hs3:141314709-141314709;hs3:77958126-77958126,hs11:27270342-27270342;hs3:77965469-77965469,hs3:191074835-191074835;hs3:78023938-78023938,hs3:79022441-79022441;hs3:78031873-78031873,hs3:195631602-195631602;hs3:78179401-78179401,hs3:97690255-97690255;hs3:78222660-78222660,hs3:148745766-148745766;hs3:78246575-78246575,hs11:56233525-56233525;hs3:78254147-78254147,hs3:103264285-103264285;hs3:78287401-78287401,hs3:142254586-142254586;hs3:78463146-78463146,hs3:180985563-180985563;hs3:78635153-78635153,hs11:41838296-41838296;hs3:78650056-78650056,hs11:111403557-111403557;hs3:78730790-78730790,hs11:125808800-125808800;hs3:78751840-78751840,hs11:38670131-38670131;hs3:78889578-78889578,hs11:25423739-25423739;hs3:78966681-78966681,hs3:112173744-112173744;hs3:79032385-79032385,hs3:167630585-167630585;hs3:79063560-79063560,hs11:61256103-61256103;hs3:79128552-79128552,hs3:165419623-165419623;hs3:79252098-79252098,hs3:163211849-163211849;hs3:79268254-79268254,hs11:16025299-16025299;hs3:79316460-79316460,hs3:97803946-97803946;hs3:79349456-79349456,hs3:129207026-129207026;hs3:79407308-79407308,hs3:96000682-96000682;hs3:79418551-79418551,hs3:193429133-193429133;hs3:79431705-79431705,hs11:37485655-37485655;hs3:79540993-79540993,hs3:132547712-132547712;hs3:79570736-79570736,hs11:129947303-129947303;hs3:79747938-79747938,hs11:65155303-65155303;hs3:79752593-79752593,hs11:110211099-110211099;hs3:79794504-79794504,hs11:40445867-40445867;hs3:79800057-79800057,hs11:85358403-85358403;hs3:79843369-79843369,hs3:154713874-154713874;hs3:79933206-79933206,hs3:166670110-166670110;hs3:80077209-80077209,hs11:81947127-81947127;hs3:80083396-80083396,hs11:55835461-55835461;hs3:80175561-80175561,hs11:25748840-25748840;hs3:80184485-80184485,hs11:49646876-49646876;hs3:80219826-80219826,hs3:186662830-186662830;hs3:80222483-80222483,hs11:33334209-33334209;hs3:80265651-80265651,hs11:10169781-10169781;hs3:80307490-80307490,hs11:77769088-77769088;hs3:80347633-80347633,hs11:11516111-11516111;hs3:80353550-80353550,hs11:122495819-122495819;hs3:80367848-80367848,hs3:133669433-133669433;hs3:80469556-80469556,hs3:121845773-121845773;hs3:80520665-80520665,hs11:9275377-9275377;hs3:80577648-80577648,hs11:3673242-3673242;hs3:80596801-80596801,hs3:188635670-188635670;hs3:80656434-80656434,hs3:166877179-166877179;hs3:80658264-80658264,hs3:190870300-190870300;hs3:80666715-80666715,hs3:145069518-145069518;hs3:80715708-80715708,hs11:7178634-7178634;hs3:80734367-80734367,hs11:133826627-133826627;hs3:80807064-80807064,hs11:58886230-58886230;hs3:80865443-80865443,hs3:143453274-143453274;hs3:80874307-80874307,hs3:87049094-87049094;hs3:80877368-80877368,hs3:170416031-170416031;hs3:80910283-80910283,hs3:120079445-120079445;hs3:81049309-81049309,hs11:25738624-25738624;hs3:81175658-81175658,hs3:122769597-122769597;hs3:81194155-81194155,hs3:101199463-101199463;hs3:81251883-81251883,hs11:98332335-98332335;hs3:81435242-81435242,hs3:160283371-160283371;hs3:81457148-81457148,hs3:97021716-97021716;hs3:81482973-81482973,hs3:110258251-110258251;hs3:81583368-81583368,hs3:148365872-148365872;hs3:81854281-81854281,hs11:41424834-41424834;hs3:81923896-81923896,hs11:13426992-13426992;hs3:81930264-81930264,hs11:15280626-15280626;hs3:81939589-81939589,hs11:67107106-67107106;hs3:81986177-81986177,hs3:187463170-187463170;hs3:82177713-82177713,hs3:83277220-83277220;hs3:82196756-82196756,hs11:18083345-18083345;hs3:82212143-82212143,hs11:124168328-124168328;hs3:82309338-82309338,hs3:105064024-105064024;hs3:82317154-82317154,hs11:57086056-57086056;hs3:82381462-82381462,hs3:111576809-111576809;hs3:82442504-82442504,hs11:47138183-47138183;hs3:82662054-82662054,hs11:29232465-29232465;hs3:82788365-82788365,hs11:108313509-108313509;hs3:82804123-82804123,hs3:88670571-88670571;hs3:82846776-82846776,hs3:100020015-100020015;hs3:82874969-82874969,hs11:81975893-81975893;hs3:82909186-82909186,hs11:24540206-24540206;hs3:83060768-83060768,hs11:112206427-112206427;hs3:83081038-83081038,hs11:120274663-120274663;hs3:83110727-83110727,hs11:37962953-37962953;hs3:83114195-83114195,hs3:125914230-125914230;hs3:83238211-83238211,hs3:112644421-112644421;hs3:83253846-83253846,hs3:145214312-145214312;hs3:83274840-83274840,hs11:95074495-95074495;hs3:83386798-83386798,hs3:136849111-136849111;hs3:83433507-83433507,hs11:22407596-22407596;hs3:83456999-83456999,hs3:184426891-184426891;hs3:83559932-83559932,hs11:24426851-24426851;hs3:83591144-83591144,hs11:108718609-108718609;hs3:83873482-83873482,hs3:179017585-179017585;hs3:83879769-83879769,hs3:168573142-168573142;hs3:84185808-84185808,hs11:134389155-134389155;hs3:84247003-84247003,hs3:172269741-172269741;hs3:84461343-84461343,hs11:26501809-26501809;hs3:84477945-84477945,hs11:117565637-117565637;hs3:84508053-84508053,hs3:135831027-135831027;hs3:84511146-84511146,hs11:47576877-47576877;hs3:84546691-84546691,hs11:14161325-14161325;hs3:84563411-84563411,hs11:6427981-6427981;hs3:84577792-84577792,hs11:16754484-16754484;hs3:84769137-84769137,hs3:154906767-154906767;hs3:84780486-84780486,hs11:134194917-134194917;hs3:84789192-84789192,hs11:61244996-61244996;hs3:84856930-84856930,hs11:48814752-48814752;hs3:84878101-84878101,hs3:173564084-173564084;hs3:84884483-84884483,hs3:196231430-196231430;hs3:84922568-84922568,hs3:195001525-195001525;hs3:84929205-84929205,hs11:59737144-59737144;hs3:84984107-84984107,hs11:132612163-132612163;hs3:85022833-85022833,hs3:179984687-179984687;hs3:85054544-85054544,hs11:82143104-82143104;hs3:85150117-85150117,hs11:13417469-13417469;hs3:85301088-85301088,hs11:130169125-130169125;hs3:85323937-85323937,hs3:155589260-155589260;hs3:85335158-85335158,hs11:63589035-63589035;hs3:85344046-85344046,hs3:85672795-85672795;hs3:85371078-85371078,hs11:113942036-113942036;hs3:85376724-85376724,hs3:102502967-102502967;hs3:85477234-85477234,hs3:109082581-109082581;hs3:85488369-85488369,hs11:21221567-21221567;hs3:85498286-85498286,hs3:122326550-122326550;hs3:85571199-85571199,hs3:187736003-187736003;hs3:85645731-85645731,hs11:38750729-38750729;hs3:85698654-85698654,hs4:49512572-49512572;hs3:85707265-85707265,hs3:176458208-176458208;hs3:85808847-85808847,hs11:19643602-19643602;hs3:85815130-85815130,hs11:49843852-49843852;hs3:85956431-85956431,hs3:182994479-182994479;hs3:85987205-85987205,hs3:177534150-177534150;hs3:86183028-86183028,hs3:190356119-190356119;hs3:86200007-86200007,hs11:32304308-32304308;hs3:86221066-86221066,hs11:113700781-113700781;hs3:86233332-86233332,hs11:66009702-66009702;hs3:86416834-86416834,hs11:105754254-105754254;hs3:86571101-86571101,hs3:88977916-88977916;hs3:86586608-86586608,hs3:103243690-103243690;hs3:86603979-86603979,hs3:140742146-140742146;hs3:86616087-86616087,hs11:91048546-91048546;hs3:86643184-86643184,hs11:78187466-78187466;hs3:86685935-86685935,hs3:101628120-101628120;hs3:86982725-86982725,hs11:98203767-98203767;hs3:86992486-86992486,hs11:18927318-18927318;hs3:87010622-87010622,hs3:168848087-168848087;hs3:87101778-87101778,hs3:152574997-152574997;hs3:87104050-87104050,hs11:115063523-115063523;hs3:87149035-87149035,hs3:98201754-98201754;hs3:87273535-87273535,hs3:112887859-112887859;hs3:87312031-87312031,hs3:119169057-119169057;hs3:87443276-87443276,hs11:100100181-100100181;hs3:87582572-87582572,hs11:7472077-7472077;hs3:87667200-87667200,hs11:89486373-89486373;hs3:87682017-87682017,hs11:211415-211415;hs3:87753560-87753560,hs11:94748399-94748399;hs3:87757566-87757566,hs11:94739916-94739916;hs3:87766513-87766513,hs3:114850709-114850709;hs3:87985151-87985151,hs3:101344872-101344872;hs3:88091502-88091502,hs11:21352052-21352052;hs3:88128719-88128719,hs3:124384849-124384849;hs3:88154800-88154800,hs3:190737289-190737289;hs3:88206091-88206091,hs3:158472569-158472569;hs3:88230465-88230465,hs11:93642563-93642563;hs3:88235140-88235140,hs3:105393093-105393093;hs3:88252799-88252799,hs11:111122059-111122059;hs3:88365882-88365882,hs11:39085913-39085913;hs3:88448889-88448889,hs11:39878594-39878594;hs3:88649911-88649911,hs11:59412352-59412352;hs3:88692594-88692594,hs3:183584919-183584919;hs3:88722653-88722653,hs3:111406807-111406807;hs3:88757291-88757291,hs3:129270809-129270809;hs3:88811714-88811714,hs3:156151436-156151436;hs3:88840397-88840397,hs11:102285130-102285130;hs3:88861217-88861217,hs3:109942992-109942992;hs3:88890100-88890100,hs3:109744074-109744074;hs3:89045241-89045241,hs3:182433557-182433557;hs3:89051884-89051884,hs3:125725039-125725039;hs3:89106278-89106278,hs11:9538560-9538560;hs3:89232417-89232417,hs3:140976539-140976539;hs3:89242879-89242879,hs3:105908438-105908438;hs3:89256331-89256331,hs3:179715429-179715429;hs3:89373427-89373427,hs11:88593642-88593642;hs3:89706945-89706945,hs11:41476668-41476668;hs3:90003060-90003060,hs11:113721706-113721706;hs3:90048656-90048656,hs11:64428934-64428934;hs3:90104106-90104106,hs11:60779831-60779831;hs3:90143299-90143299,hs3:130518520-130518520;hs3:90145592-90145592,hs11:7803507-7803507;hs3:90233591-90233591,hs3:154294999-154294999;hs3:90407621-90407621,hs11:27244666-27244666;hs3:93528601-93528601,hs11:2624976-2624976;hs3:93529414-93529414,hs3:177005136-177005136;hs3:93557894-93557894,hs11:65935424-65935424;hs3:93574683-93574683,hs11:3372457-3372457;hs3:93639724-93639724,hs11:88574578-88574578;hs3:93668010-93668010,hs11:83803232-83803232;hs3:93746535-93746535,hs3:122026907-122026907;hs3:93770860-93770860,hs11:47391026-47391026;hs3:93778933-93778933,hs3:191954855-191954855;hs3:93819843-93819843,hs11:116366985-116366985;hs3:93863756-93863756,hs3:142802041-142802041;hs3:93991571-93991571,hs11:111017364-111017364;hs3:94004476-94004476,hs3:145393025-145393025;hs3:94028561-94028561,hs11:121085145-121085145;hs3:94058850-94058850,hs3:184581025-184581025;hs3:94108191-94108191,hs11:118511282-118511282;hs3:94115456-94115456,hs11:21019365-21019365;hs3:94118568-94118568,hs11:1678184-1678184;hs3:94208571-94208571,hs11:23304483-23304483;hs3:94259378-94259378,hs3:112301844-112301844;hs3:94265870-94265870,hs11:24660417-24660417;hs3:94305549-94305549,hs21:11043994-11043994;hs3:94363069-94363069,hs3:194978417-194978417;hs3:94394684-94394684,hs3:170505662-170505662;hs3:94630107-94630107,hs11:121565037-121565037;hs3:94644513-94644513,hs3:182327590-182327590;hs3:94741222-94741222,hs11:113824223-113824223;hs3:94821484-94821484,hs11:12091598-12091598;hs3:94954305-94954305,hs11:114155710-114155710;hs3:95091706-95091706,hs3:115394079-115394079;hs3:95289851-95289851,hs3:108797192-108797192;hs3:95431238-95431238,hs11:25243609-25243609;hs3:95500246-95500246,hs3:129229848-129229848;hs3:95562627-95562627,hs11:68716366-68716366;hs3:95731390-95731390,hs3:197675795-197675795;hs3:95767159-95767159,hs3:146607280-146607280;hs3:95776704-95776704,hs11:84246642-84246642;hs3:95792836-95792836,hs3:103068515-103068515;hs3:95797291-95797291,hs3:189191737-189191737;hs3:95849186-95849186,hs11:55939330-55939330;hs3:95882352-95882352,hs11:26940184-26940184;hs3:95903847-95903847,hs11:86818200-86818200;hs3:95906219-95906219,hs11:40835219-40835219;hs3:95967137-95967137,hs3:187033733-187033733;hs3:96027668-96027668,hs11:87746195-87746195;hs3:96039496-96039496,hs3:139362112-139362112;hs3:96039737-96039737,hs11:119072176-119072176;hs3:96041865-96041865,hs3:180830440-180830440;hs3:96053903-96053903,hs11:14630228-14630228;hs3:96073445-96073445,hs3:180452302-180452302;hs3:96104500-96104500,hs11:97549735-97549735;hs3:96231089-96231089,hs11:38602215-38602215;hs3:96665307-96665307,hs3:152069261-152069261;hs3:96709097-96709097,hs4:67058-67058;hs3:96719134-96719134,hs3:107966914-107966914;hs3:96856057-96856057,hs11:119292803-119292803;hs3:96880897-96880897,hs11:39124322-39124322;hs3:96915308-96915308,hs3:197365017-197365017;hs3:96933900-96933900,hs3:99773586-99773586;hs3:97005617-97005617,hs11:36699555-36699555;hs3:97013591-97013591,hs11:8204698-8204698;hs3:97033939-97033939,hs11:47365366-47365366;hs3:97041356-97041356,hs3:157812499-157812499;hs3:97064199-97064199,hs11:20739460-20739460;hs3:97178292-97178292,hs11:118215439-118215439;hs3:97242324-97242324,hs11:58199700-58199700;hs3:97375767-97375767,hs11:100792260-100792260;hs3:97510748-97510748,hs11:46588448-46588448;hs3:97539624-97539624,hs11:61973685-61973685;hs3:97781256-97781256,hs11:32989278-32989278;hs3:97785715-97785715,hs11:44117555-44117555;hs3:97837892-97837892,hs11:79444254-79444254;hs3:97889910-97889910,hs11:111910734-111910734;hs3:97898644-97898644,hs3:146386397-146386397;hs3:97900326-97900326,hs3:180586417-180586417;hs3:98143306-98143306,hs11:86829749-86829749;hs3:98198013-98198013,hs3:103979457-103979457;hs3:98360998-98360998,hs3:104913963-104913963;hs3:98367603-98367603,hs11:128508957-128508957;hs3:98404350-98404350,hs11:3577465-3577465;hs3:98574552-98574552,hs11:50519074-50519074;hs3:98588036-98588036,hs11:43440790-43440790;hs3:98691644-98691644,hs11:97948133-97948133;hs3:98729515-98729515,hs3:138539356-138539356;hs3:98940584-98940584,hs3:164926699-164926699;hs3:98962332-98962332,hs11:131886351-131886351;hs3:98982697-98982697,hs11:87649546-87649546;hs3:98999594-98999594,hs3:180506145-180506145;hs3:99035507-99035507,hs11:4095537-4095537;hs3:99041259-99041259,hs3:186618565-186618565;hs3:99118013-99118013,hs11:39307318-39307318;hs3:99122968-99122968,hs11:102328149-102328149;hs3:99343847-99343847,hs3:109491522-109491522;hs3:99371675-99371675,hs3:101308327-101308327;hs3:99432545-99432545,hs3:142000789-142000789;hs3:99487317-99487317,hs11:100678739-100678739;hs3:99489085-99489085,hs11:27147478-27147478;hs3:99518492-99518492,hs11:22161336-22161336;hs3:99570165-99570165,hs11:2604263-2604263;hs3:99801817-99801817,hs3:127349042-127349042;hs3:99819924-99819924,hs11:36234669-36234669;hs3:99845359-99845359,hs11:27280448-27280448;hs3:99894242-99894242,hs11:110932536-110932536;hs3:100050511-100050511,hs11:126011739-126011739;hs3:100058284-100058284,hs3:196342274-196342274;hs3:100202957-100202957,hs3:100203675-100203675;hs3:100204350-100204350,hs11:84117230-84117230;hs3:100219212-100219212,hs3:158570613-158570613;hs3:100296185-100296185,hs3:173907167-173907167;hs3:100304629-100304629,hs11:87585369-87585369;hs3:100306203-100306203,hs11:28859962-28859962;hs3:100496573-100496573,hs3:136996978-136996978;hs3:100512676-100512676,hs11:67859876-67859876;hs3:100680240-100680240,hs11:120466538-120466538;hs3:100711369-100711369,hs3:168195044-168195044;hs3:100721574-100721574,hs11:25327023-25327023;hs3:100906162-100906162,hs11:60496512-60496512;hs3:100922800-100922800,hs11:32470320-32470320;hs3:101053987-101053987,hs11:218511-218511;hs3:101070834-101070834,hs11:39679005-39679005;hs3:101088666-101088666,hs3:159649698-159649698;hs3:101092882-101092882,hs11:114683284-114683284;hs3:101207022-101207022,hs11:118702095-118702095;hs3:101250377-101250377,hs11:116471326-116471326;hs3:101253216-101253216,hs11:22473276-22473276;hs3:101276872-101276872,hs3:159412170-159412170;hs3:101297808-101297808,hs3:125960474-125960474;hs3:101407219-101407219,hs11:20819016-20819016;hs3:101440389-101440389,hs3:105115285-105115285;hs3:101490591-101490591,hs11:61896062-61896062;hs3:101608149-101608149,hs3:149598594-149598594;hs3:101673037-101673037,hs3:112165292-112165292;hs3:101678576-101678576,hs3:109201722-109201722;hs3:101872017-101872017,hs11:21839450-21839450;hs3:102120064-102120064,hs3:114602188-114602188;hs3:102331184-102331184,hs11:2938708-2938708;hs3:102353284-102353284,hs3:102379132-102379132;hs3:102369633-102369633,hs11:63402750-63402750;hs3:102440310-102440310,hs11:109609065-109609065;hs3:102505551-102505551,hs11:61240011-61240011;hs3:102624614-102624614,hs3:172144210-172144210;hs3:102644996-102644996,hs3:106212305-106212305;hs3:102801752-102801752,hs3:138390628-138390628;hs3:102822958-102822958,hs11:119247762-119247762;hs3:102917740-102917740,hs11:13749702-13749702;hs3:102966317-102966317,hs11:123275914-123275914;hs3:102966316-102966316,hs11:123275913-123275913;hs3:103027440-103027440,hs3:183339700-183339700;hs3:103035826-103035826,hs11:87555014-87555014;hs3:103316917-103316917,hs11:45257372-45257372;hs3:103370991-103370991,hs3:161377867-161377867;hs3:103534504-103534504,hs3:158674270-158674270;hs3:103538712-103538712,hs11:6963936-6963936;hs3:103598492-103598492,hs11:26600118-26600118;hs3:103726962-103726962,hs3:167690497-167690497;hs3:103857176-103857176,hs3:152611150-152611150;hs3:103900280-103900280,hs11:99688175-99688175;hs3:103954506-103954506,hs3:115416227-115416227;hs3:103957614-103957614,hs3:108085931-108085931;hs3:103974858-103974858,hs3:185330652-185330652;hs3:104211109-104211109,hs11:94513937-94513937;hs3:104264141-104264141,hs11:34567439-34567439;hs3:104402620-104402620,hs11:113461135-113461135;hs3:104596802-104596802,hs11:131421663-131421663;hs3:104599211-104599211,hs3:153258517-153258517;hs3:104631445-104631445,hs11:25301085-25301085;hs3:104706224-104706224,hs11:129125706-129125706;hs3:104814706-104814706,hs11:101657533-101657533;hs3:104893908-104893908,hs3:177708182-177708182;hs3:104903711-104903711,hs11:112673520-112673520;hs3:104910266-104910266,hs11:114524087-114524087;hs3:104919082-104919082,hs11:68053768-68053768;hs3:104936628-104936628,hs3:140787623-140787623;hs3:104945328-104945328,hs3:169160064-169160064;hs3:104988326-104988326,hs3:122075922-122075922;hs3:104995394-104995394,hs11:105738678-105738678;hs3:105051473-105051473,hs3:154086782-154086782;hs3:105379563-105379563,hs3:189954431-189954431;hs3:105404871-105404871,hs11:114564864-114564864;hs3:105431883-105431883,hs11:123990079-123990079;hs3:105652855-105652855,hs3:153437553-153437553;hs3:105705460-105705460,hs3:183295072-183295072;hs3:105772137-105772137,hs3:140790788-140790788;hs3:105936354-105936354,hs11:119842701-119842701;hs3:105941113-105941113,hs3:193987924-193987924;hs3:106091201-106091201,hs11:98376240-98376240;hs3:106091201-106091201,hs11:98376240-98376240;hs3:106122509-106122509,hs11:12343627-12343627;hs3:106139411-106139411,hs11:48071536-48071536;hs3:106154242-106154242,hs11:132798574-132798574;hs3:106167575-106167575,hs11:20092319-20092319;hs3:106169732-106169732,hs3:169354636-169354636;hs3:106172096-106172096,hs11:35239026-35239026;hs3:106221211-106221211,hs3:142898604-142898604;hs3:106231641-106231641,hs3:121004979-121004979;hs3:106310413-106310413,hs3:123644006-123644006;hs3:106321005-106321005,hs3:159152919-159152919;hs3:106334880-106334880,hs11:4592109-4592109;hs3:106402713-106402713,hs3:168899774-168899774;hs3:106428655-106428655,hs11:103913630-103913630;hs3:106481772-106481772,hs11:48142117-48142117;hs3:106485062-106485062,hs3:159748739-159748739;hs3:106598568-106598568,hs3:191069743-191069743;hs3:106658668-106658668,hs11:1724551-1724551;hs3:106687596-106687596,hs11:57976777-57976777;hs3:106717964-106717964,hs3:152091399-152091399;hs3:106833815-106833815,hs3:132582004-132582004;hs3:106841208-106841208,hs3:157425800-157425800;hs3:106841913-106841913,hs3:108334772-108334772;hs3:107053195-107053195,hs11:9906909-9906909;hs3:107111082-107111082,hs3:168498175-168498175;hs3:107407225-107407225,hs11:12494705-12494705;hs3:107484871-107484871,hs3:127672561-127672561;hs3:107493236-107493236,hs11:26166929-26166929;hs3:107553894-107553894,hs11:42762823-42762823;hs3:107555900-107555900,hs3:151203537-151203537;hs3:107561566-107561566,hs3:144851541-144851541;hs3:107711539-107711539,hs3:189143171-189143171;hs3:107903131-107903131,hs3:152428603-152428603;hs3:107941610-107941610,hs11:103595779-103595779;hs3:108011952-108011952,hs3:134847923-134847923;hs3:108045174-108045174,hs11:57237001-57237001;hs3:108055732-108055732,hs11:22121106-22121106;hs3:108108261-108108261,hs11:128243451-128243451;hs3:108225619-108225619,hs11:123044778-123044778;hs3:108267219-108267219,hs11:115348059-115348059;hs3:108431532-108431532,hs3:124117961-124117961;hs3:108439185-108439185,hs11:100102910-100102910;hs3:108483613-108483613,hs3:138372450-138372450;hs3:108530161-108530161,hs3:183676085-183676085;hs3:108578149-108578149,hs3:116299907-116299907;hs3:108642329-108642329,hs3:134428587-134428587;hs3:108683891-108683891,hs11:98149725-98149725;hs3:108761699-108761699,hs11:133439517-133439517;hs3:108781759-108781759,hs3:111261379-111261379;hs3:108852664-108852664,hs11:1721404-1721404;hs3:108878505-108878505,hs11:33129262-33129262;hs3:108879499-108879499,hs3:178853585-178853585;hs3:108888561-108888561,hs3:156776887-156776887;hs3:108946596-108946596,hs11:103179317-103179317;hs3:109140772-109140772,hs3:148847251-148847251;hs3:109183102-109183102,hs11:96743553-96743553;hs3:109183943-109183943,hs11:61733465-61733465;hs3:109183944-109183944,hs11:61733466-61733466;hs3:109198971-109198971,hs11:51462347-51462347;hs3:109220380-109220380,hs11:117781020-117781020;hs3:109301280-109301280,hs3:183336697-183336697;hs3:109304795-109304795,hs3:110412253-110412253;hs3:109365835-109365835,hs11:61786638-61786638;hs3:109419665-109419665,hs3:128609024-128609024;hs3:109511437-109511437,hs11:124911196-124911196;hs3:109579560-109579560,hs11:79082764-79082764;hs3:109597872-109597872,hs3:164354204-164354204;hs3:109616259-109616259,hs3:183114763-183114763;hs3:109658330-109658330,hs11:80368741-80368741;hs3:109658728-109658728,hs11:125142607-125142607;hs3:109662673-109662673,hs3:128214451-128214451;hs3:109788421-109788421,hs11:80878260-80878260;hs3:109871728-109871728,hs3:142835748-142835748;hs3:109976350-109976350,hs11:120741155-120741155;hs3:110159236-110159236,hs11:79928602-79928602;hs3:110207075-110207075,hs3:155788144-155788144;hs3:110213736-110213736,hs3:176344519-176344519;hs3:110415276-110415276,hs11:50423324-50423324;hs3:110503756-110503756,hs11:92400577-92400577;hs3:110576308-110576308,hs3:172940403-172940403;hs3:110673197-110673197,hs3:178588493-178588493;hs3:110770016-110770016,hs11:7601482-7601482;hs3:110771370-110771370,hs11:61432916-61432916;hs3:110791320-110791320,hs3:193831222-193831222;hs3:110845850-110845850,hs11:7341028-7341028;hs3:110849861-110849861,hs11:41150573-41150573;hs3:110923017-110923017,hs3:131372580-131372580;hs3:110943825-110943825,hs11:80431491-80431491;hs3:110978278-110978278,hs3:182883750-182883750;hs3:111085781-111085781,hs11:17227656-17227656;hs3:111208082-111208082,hs11:4994776-4994776;hs3:111212054-111212054,hs3:162886891-162886891;hs3:111212971-111212971,hs11:104769863-104769863;hs3:111244021-111244021,hs11:89535360-89535360;hs3:111272943-111272943,hs3:138110021-138110021;hs3:111336554-111336554,hs3:145515389-145515389;hs3:111400509-111400509,hs11:23236751-23236751;hs3:111469248-111469248,hs3:124032491-124032491;hs3:111495808-111495808,hs11:78807340-78807340;hs3:111503793-111503793,hs3:164442738-164442738;hs3:111513314-111513314,hs11:97034343-97034343;hs3:111531796-111531796,hs11:1616885-1616885;hs3:111545215-111545215,hs11:42879650-42879650;hs3:111680135-111680135,hs11:21286415-21286415;hs3:111688292-111688292,hs3:182179150-182179150;hs3:111707654-111707654,hs3:140735718-140735718;hs3:111744066-111744066,hs11:26490778-26490778;hs3:111850659-111850659,hs11:89415675-89415675;hs3:111974183-111974183,hs3:139117027-139117027;hs3:111990242-111990242,hs3:120426171-120426171;hs3:112037606-112037606,hs11:98928371-98928371;hs3:112129033-112129033,hs11:119662622-119662622;hs3:112230826-112230826,hs3:175824643-175824643;hs3:112235947-112235947,hs11:39160482-39160482;hs3:112253267-112253267,hs11:41479809-41479809;hs3:112491186-112491186,hs11:4956944-4956944;hs3:112500348-112500348,hs11:120516913-120516913;hs3:112527135-112527135,hs3:188334984-188334984;hs3:112563110-112563110,hs6:57391709-57391709;hs3:112619816-112619816,hs3:164515078-164515078;hs3:112621228-112621228,hs3:173326799-173326799;hs3:112710502-112710502,hs11:47332433-47332433;hs3:112712239-112712239,hs11:60500171-60500171;hs3:112789342-112789342,hs11:38998567-38998567;hs3:112819355-112819355,hs11:46243801-46243801;hs3:112831145-112831145,hs11:63727459-63727459;hs3:112837018-112837018,hs3:121000668-121000668;hs3:112847690-112847690,hs11:57170079-57170079;hs3:112945725-112945725,hs11:11637083-11637083;hs3:112954746-112954746,hs11:124758728-124758728;hs3:112958381-112958381,hs11:8944344-8944344;hs3:113060494-113060494,hs11:62471963-62471963;hs3:113076671-113076671,hs3:114660235-114660235;hs3:113082964-113082964,hs11:107393205-107393205;hs3:113237825-113237825,hs3:158083388-158083388;hs3:113253465-113253465,hs11:100565306-100565306;hs3:113286247-113286247,hs11:27457030-27457030;hs3:113290070-113290070,hs3:182172816-182172816;hs3:113339645-113339645,hs11:13986313-13986313;hs3:114020729-114020729,hs3:160047552-160047552;hs3:114029684-114029684,hs3:135869275-135869275;hs3:114066323-114066323,hs3:193905430-193905430;hs3:114129200-114129200,hs11:47073077-47073077;hs3:114168245-114168245,hs3:188260712-188260712;hs3:114196287-114196287,hs3:172192599-172192599;hs3:114204001-114204001,hs11:111846180-111846180;hs3:114216293-114216293,hs3:136259262-136259262;hs3:114227716-114227716,hs11:77077366-77077366;hs3:114235493-114235493,hs11:17295450-17295450;hs3:114331882-114331882,hs11:3272179-3272179;hs3:114347147-114347147,hs3:130730800-130730800;hs3:114349254-114349254,hs3:175251274-175251274;hs3:114455306-114455306,hs11:49422284-49422284;hs3:114645062-114645062,hs3:196799299-196799299;hs3:114668402-114668402,hs11:6367585-6367585;hs3:114674132-114674132,hs11:116335954-116335954;hs3:114696577-114696577,hs11:57435084-57435084;hs3:114747302-114747302,hs11:10210911-10210911;hs3:114767837-114767837,hs11:96823616-96823616;hs3:115100168-115100168,hs3:184871909-184871909;hs3:115302966-115302966,hs11:4367749-4367749;hs3:115398421-115398421,hs11:117460816-117460816;hs3:115452122-115452122,hs11:85344753-85344753;hs3:115474374-115474374,hs11:40610519-40610519;hs3:115532193-115532193,hs3:164481341-164481341;hs3:115548770-115548770,hs11:47878333-47878333;hs3:115557304-115557304,hs11:114807169-114807169;hs3:115661447-115661447,hs11:119338208-119338208;hs3:115739168-115739168,hs3:127920293-127920293;hs3:115757875-115757875,hs11:80368073-80368073;hs3:115995027-115995027,hs11:21327559-21327559;hs3:116031011-116031011,hs3:128172170-128172170;hs3:116104773-116104773,hs11:97585871-97585871;hs3:116108662-116108662,hs3:191214281-191214281;hs3:116110921-116110921,hs3:197411575-197411575;hs3:116227186-116227186,hs11:118955311-118955311;hs3:116266202-116266202,hs3:195580926-195580926;hs3:116293955-116293955,hs11:81576843-81576843;hs3:116342077-116342077,hs11:30101170-30101170;hs3:116386199-116386199,hs11:26882089-26882089;hs3:116397686-116397686,hs3:168447948-168447948;hs3:116567673-116567673,hs3:150494696-150494696;hs3:116750449-116750449,hs3:141815273-141815273;hs3:116756811-116756811,hs3:178244800-178244800;hs3:116766720-116766720,hs11:116490031-116490031;hs3:116770147-116770147,hs11:61566179-61566179;hs3:116784004-116784004,hs11:13714225-13714225;hs3:116790115-116790115,hs21:10960359-10960359;hs3:116794109-116794109,hs11:126235229-126235229;hs3:116823297-116823297,hs3:166575626-166575626;hs3:116850819-116850819,hs11:80914549-80914549;hs3:116878793-116878793,hs3:161338614-161338614;hs3:116893345-116893345,hs3:166544550-166544550;hs3:116909198-116909198,hs3:161455758-161455758;hs3:117072545-117072545,hs3:163002406-163002406;hs3:117102175-117102175,hs11:121728105-121728105;hs3:117108468-117108468,hs3:165207904-165207904;hs3:117152682-117152682,hs11:95245605-95245605;hs3:117160260-117160260,hs11:125488500-125488500;hs3:117184228-117184228,hs11:11166094-11166094;hs3:117301515-117301515,hs3:138479313-138479313;hs3:117344867-117344867,hs11:126153205-126153205;hs3:117368092-117368092,hs11:21822375-21822375;hs3:117442334-117442334,hs11:130323563-130323563;hs3:117650631-117650631,hs11:99986775-99986775;hs3:117684742-117684742,hs11:62797488-62797488;hs3:117703609-117703609,hs3:188900386-188900386;hs3:117728969-117728969,hs3:147205544-147205544;hs3:117948310-117948310,hs11:33590347-33590347;hs3:117956228-117956228,hs3:120376796-120376796;hs3:118195285-118195285,hs11:114108351-114108351;hs3:118201358-118201358,hs3:186818105-186818105;hs3:118236611-118236611,hs11:103609881-103609881;hs3:118293055-118293055,hs11:89441497-89441497;hs3:118527609-118527609,hs11:24042349-24042349;hs3:118546691-118546691,hs11:66424348-66424348;hs3:118590385-118590385,hs11:113664062-113664062;hs3:118654977-118654977,hs11:99504958-99504958;hs3:118674640-118674640,hs3:143130721-143130721;hs3:118909187-118909187,hs3:120389955-120389955;hs3:118952019-118952019,hs3:155123122-155123122;hs3:118953888-118953888,hs11:122078453-122078453;hs3:118978097-118978097,hs11:12277899-12277899;hs3:118981061-118981061,hs11:132643914-132643914;hs3:118991829-118991829,hs11:101595879-101595879;hs3:119066981-119066981,hs11:31055624-31055624;hs3:119335806-119335806,hs11:78028479-78028479;hs3:119336918-119336918,hs3:191578749-191578749;hs3:119422440-119422440,hs11:127525329-127525329;hs3:119460727-119460727,hs3:154319008-154319008;hs3:119487509-119487509,hs11:92207753-92207753;hs3:119588142-119588142,hs11:107843822-107843822;hs3:119631739-119631739,hs15:102452286-102452286;hs3:119662663-119662663,hs11:87370347-87370347;hs3:119735538-119735538,hs3:137667466-137667466;hs3:119779611-119779611,hs11:96828562-96828562;hs3:119870137-119870137,hs11:47049515-47049515;hs3:119874573-119874573,hs11:46562258-46562258;hs3:119939315-119939315,hs11:98872209-98872209;hs3:120046868-120046868,hs11:61544576-61544576;hs3:120049819-120049819,hs3:191877771-191877771;hs3:120160253-120160253,hs11:33012963-33012963;hs3:120182867-120182867,hs3:189996382-189996382;hs3:120205905-120205905,hs11:122237377-122237377;hs3:120348506-120348506,hs11:61519949-61519949;hs3:120438774-120438774,hs11:68025938-68025938;hs3:120461570-120461570,hs11:120198919-120198919;hs3:120512377-120512377,hs11:83226069-83226069;hs3:120512474-120512474,hs3:193906657-193906657;hs3:120522870-120522870,hs3:194825192-194825192;hs3:120546694-120546694,hs3:133021080-133021080;hs3:120611340-120611340,hs11:122600630-122600630;hs3:120622434-120622434,hs11:111982085-111982085;hs3:120629526-120629526,hs3:146146085-146146085;hs3:120642819-120642819,hs21:10429107-10429107;hs3:120657928-120657928,hs11:17545839-17545839;hs3:120696651-120696651,hs11:575893-575893;hs3:120700460-120700460,hs3:170965226-170965226;hs3:120717549-120717549,hs11:63577223-63577223;hs3:120825628-120825628,hs3:161491054-161491054;hs3:120985139-120985139,hs11:40451708-40451708;hs3:120997593-120997593,hs11:39173120-39173120;hs3:121056189-121056189,hs3:126732248-126732248;hs3:121115691-121115691,hs11:12195085-12195085;hs3:121149840-121149840,hs11:98924875-98924875;hs3:121459821-121459821,hs3:125411773-125411773;hs3:121490576-121490576,hs3:168531692-168531692;hs3:121497176-121497176,hs11:37959663-37959663;hs3:121610906-121610906,hs3:167526620-167526620;hs3:121646854-121646854,hs11:114625318-114625318;hs3:121671761-121671761,hs3:177841712-177841712;hs3:121768534-121768534,hs3:178619308-178619308;hs3:121811263-121811263,hs3:191403317-191403317;hs3:121837878-121837878,hs3:171274485-171274485;hs3:121841092-121841092,hs11:134035706-134035706;hs3:121868119-121868119,hs11:47190010-47190010;hs3:121894351-121894351,hs11:128972822-128972822;hs3:121967765-121967765,hs3:160216156-160216156;hs3:121971225-121971225,hs11:38938995-38938995;hs3:122047503-122047503,hs3:195393266-195393266;hs3:122418763-122418763,hs11:67343190-67343190;hs3:122453298-122453298,hs11:29243568-29243568;hs3:122461281-122461281,hs11:113074002-113074002;hs3:122470520-122470520,hs11:35061766-35061766;hs3:122488879-122488879,hs11:113080429-113080429;hs3:122501534-122501534,hs3:177614850-177614850;hs3:122517854-122517854,hs3:148872950-148872950;hs3:122535708-122535708,hs3:192057465-192057465;hs3:122548226-122548226,hs3:191154861-191154861;hs3:122673440-122673440,hs3:123538306-123538306;hs3:122700526-122700526,hs3:136551326-136551326;hs3:122747584-122747584,hs3:169577465-169577465;hs3:122749530-122749530,hs11:17510987-17510987;hs3:122937698-122937698,hs3:189431913-189431913;hs3:122946309-122946309,hs11:27494346-27494346;hs3:123096924-123096924,hs11:97700672-97700672;hs3:123153889-123153889,hs11:45103227-45103227;hs3:123168099-123168099,hs3:186866048-186866048;hs3:123188983-123188983,hs3:155569580-155569580;hs3:123214441-123214441,hs11:134663126-134663126;hs3:123364480-123364480,hs3:154664748-154664748;hs3:123515747-123515747,hs11:60929346-60929346;hs3:123521494-123521494,hs11:25632426-25632426;hs3:123559196-123559196,hs3:147933656-147933656;hs3:123662679-123662679,hs3:164978593-164978593;hs3:123762624-123762624,hs11:67766947-67766947;hs3:123912386-123912386,hs11:57993037-57993037;hs3:123923664-123923664,hs3:173367151-173367151;hs3:124039373-124039373,hs11:97714043-97714043;hs3:124051733-124051733,hs3:124099385-124099385;hs3:124069863-124069863,hs3:155797622-155797622;hs3:124147935-124147935,hs3:180408555-180408555;hs3:124221422-124221422,hs11:12019812-12019812;hs3:124270910-124270910,hs11:92965824-92965824;hs3:124377142-124377142,hs11:44218894-44218894;hs3:124520142-124520142,hs3:169133233-169133233;hs3:124532712-124532712,hs11:92812140-92812140;hs3:124640248-124640248,hs11:115126235-115126235;hs3:124824509-124824509,hs3:181375908-181375908;hs3:124835502-124835502,hs3:140309712-140309712;hs3:125057289-125057289,hs11:81908922-81908922;hs3:125099951-125099951,hs3:187474166-187474166;hs3:125126771-125126771,hs11:121572066-121572066;hs3:125168964-125168964,hs11:63285792-63285792;hs3:125223464-125223464,hs11:47569595-47569595;hs3:125320407-125320407,hs11:7269245-7269245;hs3:125329643-125329643,hs11:17462883-17462883;hs3:125341309-125341309,hs11:81067669-81067669;hs3:125465770-125465770,hs11:110624448-110624448;hs3:125626596-125626596,hs11:23645934-23645934;hs3:125726988-125726988,hs3:153196970-153196970;hs3:125838919-125838919,hs11:92850784-92850784;hs3:125880326-125880326,hs3:191084962-191084962;hs3:126014070-126014070,hs11:128772894-128772894;hs3:126014750-126014750,hs11:31586743-31586743;hs3:126048638-126048638,hs11:8564881-8564881;hs3:126188834-126188834,hs11:16506354-16506354;hs3:126215227-126215227,hs11:63393682-63393682;hs3:126306758-126306758,hs3:160060436-160060436;hs3:126408355-126408355,hs11:96747536-96747536;hs3:126531725-126531725,hs11:78947476-78947476;hs3:126538992-126538992,hs11:129843574-129843574;hs3:126560517-126560517,hs3:170529146-170529146;hs3:126620076-126620076,hs3:181651878-181651878;hs3:126700852-126700852,hs11:4759319-4759319;hs3:126871665-126871665,hs11:32552287-32552287;hs3:126985492-126985492,hs11:35293324-35293324;hs3:127011922-127011922,hs3:164721381-164721381;hs3:127132711-127132711,hs3:141529568-141529568;hs3:127143459-127143459,hs3:189436266-189436266;hs3:127292159-127292159,hs3:183431037-183431037;hs3:127327741-127327741,hs11:106797927-106797927;hs3:127329104-127329104,hs11:17891091-17891091;hs3:127358106-127358106,hs3:141504129-141504129;hs3:127363711-127363711,hs3:129753277-129753277;hs3:127370463-127370463,hs11:17979241-17979241;hs3:127405688-127405688,hs11:33110838-33110838;hs3:127405687-127405687,hs11:33110839-33110839;hs3:127537724-127537724,hs11:87064679-87064679;hs3:127538695-127538695,hs3:163513564-163513564;hs3:127737004-127737004,hs3:193261217-193261217;hs3:127771001-127771001,hs11:7315413-7315413;hs3:127845993-127845993,hs11:37768022-37768022;hs3:127875453-127875453,hs3:146430461-146430461;hs3:128050291-128050291,hs11:11391145-11391145;hs3:128378287-128378287,hs11:25619013-25619013;hs3:128390904-128390904,hs3:189598738-189598738;hs3:128394102-128394102,hs11:64698136-64698136;hs3:128454489-128454489,hs3:166351580-166351580;hs3:128563005-128563005,hs3:170623179-170623179;hs3:128579927-128579927,hs11:130664215-130664215;hs3:128585119-128585119,hs11:13369110-13369110;hs3:128589484-128589484,hs3:155597584-155597584;hs3:128638642-128638642,hs11:39279136-39279136;hs3:128648078-128648078,hs3:183423559-183423559;hs3:128680449-128680449,hs11:51411421-51411421;hs3:128715050-128715050,hs3:171316965-171316965;hs3:128869239-128869239,hs11:62717768-62717768;hs3:129003409-129003409,hs11:783177-783177;hs3:129024311-129024311,hs11:15712246-15712246;hs3:129045995-129045995,hs11:95688640-95688640;hs3:129224662-129224662,hs3:196068088-196068088;hs3:129285665-129285665,hs11:23423212-23423212;hs3:129301129-129301129,hs11:8030144-8030144;hs3:129303933-129303933,hs11:119876471-119876471;hs3:129409636-129409636,hs11:91620427-91620427;hs3:129437811-129437811,hs11:26455126-26455126;hs3:129551019-129551019,hs11:19066053-19066053;hs3:129570923-129570923,hs3:177718153-177718153;hs3:129618502-129618502,hs3:145908353-145908353;hs3:129644585-129644585,hs3:194649548-194649548;hs3:129752307-129752307,hs11:118984565-118984565;hs3:129830574-129830574,hs11:15559840-15559840;hs3:129973178-129973178,hs11:129411561-129411561;hs3:130020034-130020034,hs3:136707620-136707620;hs3:130062356-130062356,hs3:163660891-163660891;hs3:130169433-130169433,hs11:16954955-16954955;hs3:130202114-130202114,hs11:83153314-83153314;hs3:130246714-130246714,hs11:63488753-63488753;hs3:130409230-130409230,hs11:5160519-5160519;hs3:130410226-130410226,hs11:107852241-107852241;hs3:130528633-130528633,hs11:31596634-31596634;hs3:130578369-130578369,hs11:99629771-99629771;hs3:130614368-130614368,hs11:87208330-87208330;hs3:130647519-130647519,hs3:153729355-153729355;hs3:130659588-130659588,hs3:160589655-160589655;hs3:130713670-130713670,hs3:166308730-166308730;hs3:130874472-130874472,hs3:163629218-163629218;hs3:130918579-130918579,hs11:131198267-131198267;hs3:130957247-130957247,hs3:133027633-133027633;hs3:130992417-130992417,hs11:14710827-14710827;hs3:131003241-131003241,hs3:171230624-171230624;hs3:131064837-131064837,hs11:41413330-41413330;hs3:131203717-131203717,hs3:196353019-196353019;hs3:131281650-131281650,hs11:22159831-22159831;hs3:131284714-131284714,hs11:127321617-127321617;hs3:131295659-131295659,hs3:158556071-158556071;hs3:131311853-131311853,hs11:90905979-90905979;hs3:131344150-131344150,hs3:156079398-156079398;hs3:131395742-131395742,hs3:150888342-150888342;hs3:131397940-131397940,hs3:164961488-164961488;hs3:131456880-131456880,hs11:55928989-55928989;hs3:131469422-131469422,hs3:150305362-150305362;hs3:131663281-131663281,hs3:171015060-171015060;hs3:131700240-131700240,hs11:87990986-87990986;hs3:131786475-131786475,hs3:195571224-195571224;hs3:131791584-131791584,hs3:189046296-189046296;hs3:131837065-131837065,hs11:131691516-131691516;hs3:131933479-131933479,hs11:129561396-129561396;hs3:131946645-131946645,hs3:142381647-142381647;hs3:132156859-132156859,hs11:90431129-90431129;hs3:132172571-132172571,hs11:129676749-129676749;hs3:132194086-132194086,hs11:25331673-25331673;hs3:132205250-132205250,hs3:161884023-161884023;hs3:132552168-132552168,hs11:35320129-35320129;hs3:132963951-132963951,hs11:104625792-104625792;hs3:133245894-133245894,hs11:114585860-114585860;hs3:133312855-133312855,hs3:186750644-186750644;hs3:133431468-133431468,hs11:86786315-86786315;hs3:133556853-133556853,hs11:40963413-40963413;hs3:133559473-133559473,hs11:36434653-36434653;hs3:133695882-133695882,hs11:39693873-39693873;hs3:133742249-133742249,hs3:184068825-184068825;hs3:133775828-133775828,hs11:94489534-94489534;hs3:133822025-133822025,hs11:41682353-41682353;hs3:133826092-133826092,hs11:105941167-105941167;hs3:133936492-133936492,hs11:108972633-108972633;hs3:133960828-133960828,hs11:125310305-125310305;hs3:134002711-134002711,hs11:97763583-97763583;hs3:134032245-134032245,hs11:58767448-58767448;hs3:134146036-134146036,hs11:99841966-99841966;hs3:134179353-134179353,hs11:111473278-111473278;hs3:134332332-134332332,hs3:134929419-134929419;hs3:134346956-134346956,hs11:46732939-46732939;hs3:134432822-134432822,hs3:179573156-179573156;hs3:134458703-134458703,hs3:182188253-182188253;hs3:134631799-134631799,hs11:101557719-101557719;hs3:134669838-134669838,hs11:110182337-110182337;hs3:134690432-134690432,hs11:103802013-103802013;hs3:134703238-134703238,hs11:56179190-56179190;hs3:134887665-134887665,hs3:172354602-172354602;hs3:134901137-134901137,hs3:195911849-195911849;hs3:134940458-134940458,hs3:176236359-176236359;hs3:135042568-135042568,hs11:57016824-57016824;hs3:135164249-135164249,hs11:125877752-125877752;hs3:135169636-135169636,hs3:160946961-160946961;hs3:135179225-135179225,hs3:186874018-186874018;hs3:135179945-135179945,hs11:110630255-110630255;hs3:135235798-135235798,hs11:79147478-79147478;hs3:135348578-135348578,hs3:139123317-139123317;hs3:135387844-135387844,hs11:110743859-110743859;hs3:135404395-135404395,hs11:26709720-26709720;hs3:135448585-135448585,hs11:38788673-38788673;hs3:135452953-135452953,hs11:63272550-63272550;hs3:135455946-135455946,hs3:139092100-139092100;hs3:135469979-135469979,hs11:109436077-109436077;hs3:135510301-135510301,hs3:135603581-135603581;hs3:135594783-135594783,hs3:135595893-135595893;hs3:135711345-135711345,hs11:120544882-120544882;hs3:135818658-135818658,hs11:120425502-120425502;hs3:135835926-135835926,hs11:79942311-79942311;hs3:135854189-135854189,hs11:67174184-67174184;hs3:136028327-136028327,hs3:168363086-168363086;hs3:136132105-136132105,hs11:128780845-128780845;hs3:136218712-136218712,hs11:103067245-103067245;hs3:136466799-136466799,hs11:102901577-102901577;hs3:136467761-136467761,hs11:40242513-40242513;hs3:136530954-136530954,hs11:82282684-82282684;hs3:136587874-136587874,hs11:34900008-34900008;hs3:136621620-136621620,hs11:130677300-130677300;hs3:136700650-136700650,hs11:124763837-124763837;hs3:136780031-136780031,hs3:162268738-162268738;hs3:136998522-136998522,hs3:189758618-189758618;hs3:137010808-137010808,hs3:148907169-148907169;hs3:137015580-137015580,hs11:42595344-42595344;hs3:137016384-137016384,hs11:44536486-44536486;hs3:137016384-137016384,hs11:44536487-44536487;hs3:137018545-137018545,hs3:193908285-193908285;hs3:137074603-137074603,hs11:47851051-47851051;hs3:137091767-137091767,hs3:164493823-164493823;hs3:137290111-137290111,hs11:30032787-30032787;hs3:137342886-137342886,hs3:143808888-143808888;hs3:137429534-137429534,hs11:21398566-21398566;hs3:137526102-137526102,hs11:16740183-16740183;hs3:137619894-137619894,hs11:112797749-112797749;hs3:137965774-137965774,hs11:8185951-8185951;hs3:137997623-137997623,hs11:77264757-77264757;hs3:138011088-138011088,hs11:7813418-7813418;hs3:138062832-138062832,hs3:163718380-163718380;hs3:138174279-138174279,hs3:196486081-196486081;hs3:138246968-138246968,hs11:21891268-21891268;hs3:138273337-138273337,hs11:50697987-50697987;hs3:138278523-138278523,hs11:27161232-27161232;hs3:138365291-138365291,hs3:184315386-184315386;hs3:138378248-138378248,hs11:16599092-16599092;hs3:138411779-138411779,hs11:94684324-94684324;hs3:138590383-138590383,hs3:158323733-158323733;hs3:138602388-138602388,hs11:132971717-132971717;hs3:138604595-138604595,hs11:84253088-84253088;hs3:138824014-138824014,hs3:150101013-150101013;hs3:138975458-138975458,hs11:10201241-10201241;hs3:138977040-138977040,hs11:124753340-124753340;hs3:139036578-139036578,hs3:172129599-172129599;hs3:139037896-139037896,hs11:129792747-129792747;hs3:139042227-139042227,hs11:4997027-4997027;hs3:139073540-139073540,hs11:68519994-68519994;hs3:139402234-139402234,hs11:6627310-6627310;hs3:139450403-139450403,hs11:123554952-123554952;hs3:139501105-139501105,hs11:105730775-105730775;hs3:139503383-139503383,hs11:78678339-78678339;hs3:139802960-139802960,hs11:113255257-113255257;hs3:139812784-139812784,hs11:60698610-60698610;hs3:139853279-139853279,hs11:28265111-28265111;hs3:139928323-139928323,hs3:179843335-179843335;hs3:139956363-139956363,hs11:77657323-77657323;hs3:140174220-140174220,hs3:174790861-174790861;hs3:140189700-140189700,hs11:126371631-126371631;hs3:140190064-140190064,hs11:86226574-86226574;hs3:140197436-140197436,hs3:163750193-163750193;hs3:140231927-140231927,hs11:90862065-90862065;hs3:140565547-140565547,hs11:48462423-48462423;hs3:140567601-140567601,hs11:23154754-23154754;hs3:140587102-140587102,hs11:66178662-66178662;hs3:140588472-140588472,hs11:64392135-64392135;hs3:140591108-140591108,hs11:9108973-9108973;hs3:140670481-140670481,hs11:9535149-9535149;hs3:140712003-140712003,hs11:113610073-113610073;hs3:140800948-140800948,hs11:113248099-113248099;hs3:140809179-140809179,hs11:126174662-126174662;hs3:141032747-141032747,hs11:10819583-10819583;hs3:141053368-141053368,hs11:122985201-122985201;hs3:141213116-141213116,hs11:94751330-94751330;hs3:141275350-141275350,hs11:33415039-33415039;hs3:141304186-141304186,hs3:166367538-166367538;hs3:141308417-141308417,hs11:22405684-22405684;hs3:141350274-141350274,hs11:113633885-113633885;hs3:141361990-141361990,hs11:98697971-98697971;hs3:141379580-141379580,hs21:10705592-10705592;hs3:141415096-141415096,hs11:68008138-68008138;hs3:141524225-141524225,hs11:89413374-89413374;hs3:141554476-141554476,hs3:152675215-152675215;hs3:141577183-141577183,hs11:27403819-27403819;hs3:141681051-141681051,hs11:28634895-28634895;hs3:141853565-141853565,hs11:121624831-121624831;hs3:141984436-141984436,hs3:181097710-181097710;hs3:142186033-142186033,hs3:182245958-182245958;hs3:142251005-142251005,hs11:96573924-96573924;hs3:142287172-142287172,hs11:2914110-2914110;hs3:142302883-142302883,hs11:113469487-113469487;hs3:142309128-142309128,hs3:176682709-176682709;hs3:142448843-142448843,hs11:93114133-93114133;hs3:142470082-142470082,hs11:46752001-46752001;hs3:142476496-142476496,hs3:168128429-168128429;hs3:142713714-142713714,hs3:146226302-146226302;hs3:142815489-142815489,hs11:89818442-89818442;hs3:142892835-142892835,hs11:87562075-87562075;hs3:142959104-142959104,hs11:30081979-30081979;hs3:143000986-143000986,hs11:17905912-17905912;hs3:143004321-143004321,hs11:91108283-91108283;hs3:143120707-143120707,hs11:125712556-125712556;hs3:143279790-143279790,hs11:22213189-22213189;hs3:143296344-143296344,hs3:152363013-152363013;hs3:143346675-143346675,hs11:41791029-41791029;hs3:143479313-143479313,hs11:64325721-64325721;hs3:143480793-143480793,hs3:195015333-195015333;hs3:143818363-143818363,hs11:9195175-9195175;hs3:144230435-144230435,hs3:157827332-157827332;hs3:144255754-144255754,hs11:122368396-122368396;hs3:144631747-144631747,hs11:3401290-3401290;hs3:144847967-144847967,hs11:12809757-12809757;hs3:144989631-144989631,hs11:55234705-55234705;hs3:145081248-145081248,hs3:185361343-185361343;hs3:145099990-145099990,hs3:156995350-156995350;hs3:145434154-145434154,hs3:186144435-186144435;hs3:145442367-145442367,hs11:21133687-21133687;hs3:145511079-145511079,hs11:14701425-14701425;hs3:145517070-145517070,hs11:56713804-56713804;hs3:145538569-145538569,hs3:167994147-167994147;hs3:145623058-145623058,hs11:128503429-128503429;hs3:145630180-145630180,hs11:40904313-40904313;hs3:145658435-145658435,hs11:125577345-125577345;hs3:145771878-145771878,hs3:166967023-166967023;hs3:145837402-145837402,hs3:160315915-160315915;hs3:145864284-145864284,hs3:184789149-184789149;hs3:145899111-145899111,hs3:185357084-185357084;hs3:146162741-146162741,hs11:3335730-3335730;hs3:146194525-146194525,hs11:101180794-101180794;hs3:146210084-146210084,hs3:190696051-190696051;hs3:146294202-146294202,hs3:162729628-162729628;hs3:146411164-146411164,hs11:8945161-8945161;hs3:146468907-146468907,hs11:123275665-123275665;hs3:146490632-146490632,hs11:59868748-59868748;hs3:146559591-146559591,hs11:79237029-79237029;hs3:146597110-146597110,hs11:27330546-27330546;hs3:146624644-146624644,hs11:94040387-94040387;hs3:146628633-146628633,hs11:5600565-5600565;hs3:146661818-146661818,hs11:124509590-124509590;hs3:146673189-146673189,hs11:66251330-66251330;hs3:146687963-146687963,hs11:84583252-84583252;hs3:146732056-146732056,hs11:131891401-131891401;hs3:146855410-146855410,hs11:85095481-85095481;hs3:146858502-146858502,hs3:176897392-176897392;hs3:147187140-147187140,hs11:1444804-1444804;hs3:147261883-147261883,hs11:86197147-86197147;hs3:147458349-147458349,hs3:184247312-184247312;hs3:147510116-147510116,hs11:87748443-87748443;hs3:147595548-147595548,hs3:147906665-147906665;hs3:147599050-147599050,hs11:111735916-111735916;hs3:147785785-147785785,hs11:7667323-7667323;hs3:147826293-147826293,hs3:182948381-182948381;hs3:147899992-147899992,hs11:20428090-20428090;hs3:147943893-147943893,hs11:91622202-91622202;hs3:147968298-147968298,hs11:6556520-6556520;hs3:148027814-148027814,hs3:185143394-185143394;hs3:148116095-148116095,hs11:23827351-23827351;hs3:148223256-148223256,hs3:164321664-164321664;hs3:148248464-148248464,hs3:196791190-196791190;hs3:148291624-148291624,hs11:38126245-38126245;hs3:148306867-148306867,hs3:160335704-160335704;hs3:148363820-148363820,hs3:196404794-196404794;hs3:148393212-148393212,hs11:23993802-23993802;hs3:148457547-148457547,hs3:191028680-191028680;hs3:148459082-148459082,hs3:196457583-196457583;hs3:148496443-148496443,hs11:117710744-117710744;hs3:148507909-148507909,hs11:125771729-125771729;hs3:148874502-148874502,hs11:81189862-81189862;hs3:148928299-148928299,hs3:180864870-180864870;hs3:148994580-148994580,hs3:154902008-154902008;hs3:149006211-149006211,hs11:112024156-112024156;hs3:149037433-149037433,hs11:56086110-56086110;hs3:149077395-149077395,hs11:102939818-102939818;hs3:149096006-149096006,hs11:113383883-113383883;hs3:149180865-149180865,hs11:92238171-92238171;hs3:149290425-149290425,hs11:1725148-1725148;hs3:149482122-149482122,hs11:5746668-5746668;hs3:149537532-149537532,hs11:117619177-117619177;hs3:149548605-149548605,hs11:124854563-124854563;hs3:149607164-149607164,hs11:11889502-11889502;hs3:149635950-149635950,hs11:78102638-78102638;hs3:149747170-149747170,hs3:191940603-191940603;hs3:149974099-149974099,hs3:180774271-180774271;hs3:150211511-150211511,hs11:39209711-39209711;hs3:150309520-150309520,hs3:151832747-151832747;hs3:150316546-150316546,hs11:125268610-125268610;hs3:150549030-150549030,hs11:94457132-94457132;hs3:150554467-150554467,hs11:90720401-90720401;hs3:150581403-150581403,hs3:162262372-162262372;hs3:150635633-150635633,hs3:188519765-188519765;hs3:150656426-150656426,hs11:28616208-28616208;hs3:150850816-150850816,hs3:173862455-173862455;hs3:150873437-150873437,hs11:129935772-129935772;hs3:150910036-150910036,hs3:173299321-173299321;hs3:150957222-150957222,hs11:65931930-65931930;hs3:151044200-151044200,hs11:3150733-3150733;hs3:151057705-151057705,hs11:3694504-3694504;hs3:151084684-151084684,hs11:107974691-107974691;hs3:151188713-151188713,hs11:98910570-98910570;hs3:151221527-151221527,hs3:180841355-180841355;hs3:151275915-151275915,hs3:174469382-174469382;hs3:151308803-151308803,hs11:95220807-95220807;hs3:151571037-151571037,hs11:132624355-132624355;hs3:151732975-151732975,hs11:5290012-5290012;hs3:151747961-151747961,hs11:101149858-101149858;hs3:151749034-151749034,hs11:101138284-101138284;hs3:151768728-151768728,hs11:15872933-15872933;hs3:152001866-152001866,hs11:34188067-34188067;hs3:152044384-152044384,hs11:94653931-94653931;hs3:152044384-152044384,hs11:94653932-94653932;hs3:152055350-152055350,hs11:84641676-84641676;hs3:152125320-152125320,hs11:6454951-6454951;hs3:152131621-152131621,hs3:177044317-177044317;hs3:152146663-152146663,hs3:194753041-194753041;hs3:152269806-152269806,hs11:131149495-131149495;hs3:152359871-152359871,hs11:34778964-34778964;hs3:152447485-152447485,hs11:67154144-67154144;hs3:152453846-152453846,hs3:185215323-185215323;hs3:152526109-152526109,hs11:88708016-88708016;hs3:152544560-152544560,hs3:182261572-182261572;hs3:152573700-152573700,hs3:190583877-190583877;hs3:152668318-152668318,hs3:155034723-155034723;hs3:152681813-152681813,hs11:36472553-36472553;hs3:152688685-152688685,hs11:125036698-125036698;hs3:153012928-153012928,hs11:89153460-89153460;hs3:153126780-153126780,hs11:67304634-67304634;hs3:153165412-153165412,hs11:134824984-134824984;hs3:153411281-153411281,hs11:39464447-39464447;hs3:153647002-153647002,hs11:47027587-47027587;hs3:153651374-153651374,hs11:60712766-60712766;hs3:153818709-153818709,hs11:11906899-11906899;hs3:153821434-153821434,hs3:193274644-193274644;hs3:153851400-153851400,hs11:118408095-118408095;hs3:154141214-154141214,hs11:85465524-85465524;hs3:154294258-154294258,hs11:79407667-79407667;hs3:154336180-154336180,hs11:38557038-38557038;hs3:154341837-154341837,hs11:128841682-128841682;hs3:154535907-154535907,hs3:161331529-161331529;hs3:154544724-154544724,hs11:65248997-65248997;hs3:154564355-154564355,hs11:60241010-60241010;hs3:154601826-154601826,hs11:127224171-127224171;hs3:154658341-154658341,hs11:108858363-108858363;hs3:154687660-154687660,hs3:156682049-156682049;hs3:154692119-154692119,hs11:31600261-31600261;hs3:154748767-154748767,hs11:21219328-21219328;hs3:154749588-154749588,hs11:120241930-120241930;hs3:154881906-154881906,hs11:120548819-120548819;hs3:154908186-154908186,hs11:122905483-122905483;hs3:155088850-155088850,hs11:106479232-106479232;hs3:155103023-155103023,hs11:16753099-16753099;hs3:155164162-155164162,hs11:56896269-56896269;hs3:155216658-155216658,hs21:11109148-11109148;hs3:155286814-155286814,hs11:3136589-3136589;hs3:155297010-155297010,hs11:49637094-49637094;hs3:155363160-155363160,hs11:87225950-87225950;hs3:155461703-155461703,hs11:31461800-31461800;hs3:155476653-155476653,hs11:55804986-55804986;hs3:155574691-155574691,hs3:156612366-156612366;hs3:155699644-155699644,hs11:26535372-26535372;hs3:155770391-155770391,hs11:41328504-41328504;hs3:155804048-155804048,hs11:108494516-108494516;hs3:155837263-155837263,hs3:179222184-179222184;hs3:155840242-155840242,hs11:65817198-65817198;hs3:155869603-155869603,hs3:170805657-170805657;hs3:155971215-155971215,hs11:21934196-21934196;hs3:156077914-156077914,hs11:96067699-96067699;hs3:156115254-156115254,hs11:41344496-41344496;hs3:156128342-156128342,hs11:45568334-45568334;hs3:156144430-156144430,hs11:85389077-85389077;hs3:156277495-156277495,hs11:28084872-28084872;hs3:156303686-156303686,hs3:170347061-170347061;hs3:156485362-156485362,hs3:175132895-175132895;hs3:156494628-156494628,hs11:109107904-109107904;hs3:156552463-156552463,hs11:60159541-60159541;hs3:156602390-156602390,hs11:103432520-103432520;hs3:156779718-156779718,hs3:189478451-189478451;hs3:156793320-156793320,hs11:55671563-55671563;hs3:156836054-156836054,hs11:2372517-2372517;hs3:156836423-156836423,hs11:102055224-102055224;hs3:156907120-156907120,hs3:157814540-157814540;hs3:157130246-157130246,hs3:181465462-181465462;hs3:157228111-157228111,hs11:21694692-21694692;hs3:157252694-157252694,hs3:161329262-161329262;hs3:157270622-157270622,hs3:179063385-179063385;hs3:157378346-157378346,hs11:101026171-101026171;hs3:157468786-157468786,hs11:14127190-14127190;hs3:157571011-157571011,hs3:181141861-181141861;hs3:157601830-157601830,hs11:8458193-8458193;hs3:158291808-158291808,hs11:110918141-110918141;hs3:158346259-158346259,hs11:123810119-123810119;hs3:158400284-158400284,hs11:97754582-97754582;hs3:158455616-158455616,hs11:10935894-10935894;hs3:158572378-158572378,hs3:195336882-195336882;hs3:158657621-158657621,hs11:12973108-12973108;hs3:158775488-158775488,hs11:42783325-42783325;hs3:158950309-158950309,hs3:181075849-181075849;hs3:158977550-158977550,hs3:192072582-192072582;hs3:159026811-159026811,hs11:15952329-15952329;hs3:159139553-159139553,hs3:177988265-177988265;hs3:159183816-159183816,hs11:58458700-58458700;hs3:159194689-159194689,hs3:166235508-166235508;hs3:159263548-159263548,hs11:29487501-29487501;hs3:159275333-159275333,hs11:15965127-15965127;hs3:159359705-159359705,hs3:189163554-189163554;hs3:159364918-159364918,hs11:108189641-108189641;hs3:159370585-159370585,hs11:26786726-26786726;hs3:159383204-159383204,hs3:195277686-195277686;hs3:159418614-159418614,hs11:81888387-81888387;hs3:159595626-159595626,hs11:95928079-95928079;hs3:159611484-159611484,hs3:163526381-163526381;hs3:159798849-159798849,hs3:182943658-182943658;hs3:159844024-159844024,hs11:34013115-34013115;hs3:159847933-159847933,hs11:15449058-15449058;hs3:159854977-159854977,hs11:90260862-90260862;hs3:159868058-159868058,hs11:24465802-24465802;hs3:160026333-160026333,hs3:172737461-172737461;hs3:160090318-160090318,hs3:179989920-179989920;hs3:160299598-160299598,hs11:4259187-4259187;hs3:160299597-160299597,hs11:4259187-4259187;hs3:160364360-160364360,hs11:31073414-31073414;hs3:160385186-160385186,hs11:3381050-3381050;hs3:160410893-160410893,hs11:112989515-112989515;hs3:160740038-160740038,hs11:110960967-110960967;hs3:160757756-160757756,hs11:127217376-127217376;hs3:160815410-160815410,hs11:37566614-37566614;hs3:160921801-160921801,hs11:133874532-133874532;hs3:161100485-161100485,hs11:40173786-40173786;hs3:161166825-161166825,hs11:106998940-106998940;hs3:161275658-161275658,hs11:106522982-106522982;hs3:161394011-161394011,hs11:128251451-128251451;hs3:161465923-161465923,hs11:55918397-55918397;hs3:161488994-161488994,hs3:173543058-173543058;hs3:161528799-161528799,hs11:22816628-22816628;hs3:161542293-161542293,hs11:128866180-128866180;hs3:161562638-161562638,hs11:24729095-24729095;hs3:161590526-161590526,hs3:177716425-177716425;hs3:161722140-161722140,hs11:119048730-119048730;hs3:161785653-161785653,hs11:125206344-125206344;hs3:161845103-161845103,hs3:169041811-169041811;hs3:161854614-161854614,hs3:162211708-162211708;hs3:161898608-161898608,hs11:63642835-63642835;hs3:161943688-161943688,hs11:81261188-81261188;hs3:161995697-161995697,hs11:12187390-12187390;hs3:161998601-161998601,hs3:167403992-167403992;hs3:162061213-162061213,hs11:118911419-118911419;hs3:162093440-162093440,hs11:55329099-55329099;hs3:162220560-162220560,hs11:28805158-28805158;hs3:162317207-162317207,hs11:62609193-62609193;hs3:162742298-162742298,hs3:179523191-179523191;hs3:162888628-162888628,hs11:34481949-34481949;hs3:163081189-163081189,hs3:171538484-171538484;hs3:163117415-163117415,hs11:60381177-60381177;hs3:163151332-163151332,hs11:78649285-78649285;hs3:163216460-163216460,hs3:193679757-193679757;hs3:163233973-163233973,hs3:181082362-181082362;hs3:163244800-163244800,hs3:176333965-176333965;hs3:163263616-163263616,hs11:27756813-27756813;hs3:163709350-163709350,hs11:4931796-4931796;hs3:163805782-163805782,hs3:184549862-184549862;hs3:163945343-163945343,hs11:95803002-95803002;hs3:164086689-164086689,hs11:91930169-91930169;hs3:164104851-164104851,hs11:95011395-95011395;hs3:164334161-164334161,hs3:194676220-194676220;hs3:164360716-164360716,hs11:131757252-131757252;hs3:164423046-164423046,hs3:167952197-167952197;hs3:164437951-164437951,hs11:45867300-45867300;hs3:164468113-164468113,hs11:90984430-90984430;hs3:164663545-164663545,hs11:101581891-101581891;hs3:164679331-164679331,hs11:9568243-9568243;hs3:164749676-164749676,hs3:164773911-164773911;hs3:164766878-164766878,hs11:10506683-10506683;hs3:164775316-164775316,hs11:47531226-47531226;hs3:164777046-164777046,hs11:48614129-48614129;hs3:164922986-164922986,hs3:170656116-170656116;hs3:164965638-164965638,hs11:31254052-31254052;hs3:165006729-165006729,hs11:757082-757082;hs3:165154049-165154049,hs11:111459326-111459326;hs3:165182331-165182331,hs3:169639243-169639243;hs3:165521926-165521926,hs11:128482538-128482538;hs3:165604937-165604937,hs11:80026589-80026589;hs3:165883026-165883026,hs3:175485399-175485399;hs3:165909408-165909408,hs3:174753053-174753053;hs3:166085855-166085855,hs11:81334471-81334471;hs3:166163076-166163076,hs3:192172793-192172793;hs3:166205205-166205205,hs3:177446625-177446625;hs3:166218030-166218030,hs11:105527471-105527471;hs3:166228539-166228539,hs11:33000448-33000448;hs3:166252814-166252814,hs11:116890913-116890913;hs3:166307066-166307066,hs3:169268115-169268115;hs3:166542406-166542406,hs3:181190979-181190979;hs3:166657510-166657510,hs11:132617665-132617665;hs3:166797370-166797370,hs3:174814984-174814984;hs3:166964341-166964341,hs11:95534783-95534783;hs3:167125985-167125985,hs11:133025965-133025965;hs3:167208472-167208472,hs11:34661634-34661634;hs3:167220424-167220424,hs11:39698982-39698982;hs3:167427713-167427713,hs11:98384814-98384814;hs3:167501857-167501857,hs11:10312854-10312854;hs3:167514467-167514467,hs11:77650198-77650198;hs3:167553890-167553890,hs11:77055275-77055275;hs3:167949178-167949178,hs11:64861597-64861597;hs3:168055078-168055078,hs11:20891560-20891560;hs3:168160851-168160851,hs3:182838980-182838980;hs3:168200836-168200836,hs11:67284140-67284140;hs3:168314619-168314619,hs11:126029650-126029650;hs3:168345726-168345726,hs11:30523789-30523789;hs3:168437987-168437987,hs3:176561182-176561182;hs3:168629392-168629392,hs11:95426324-95426324;hs3:168638299-168638299,hs11:38535214-38535214;hs3:168705826-168705826,hs3:180032323-180032323;hs3:168903199-168903199,hs11:34550236-34550236;hs3:168998045-168998045,hs11:6271811-6271811;hs3:169034668-169034668,hs3:171094541-171094541;hs3:169198882-169198882,hs3:175972764-175972764;hs3:169281864-169281864,hs3:191798314-191798314;hs3:169357824-169357824,hs11:18234291-18234291;hs3:169376271-169376271,hs3:187419035-187419035;hs3:169378292-169378292,hs11:100426941-100426941;hs3:169433617-169433617,hs11:130188385-130188385;hs3:169521723-169521723,hs11:124120715-124120715;hs3:169532052-169532052,hs11:49631989-49631989;hs3:169585352-169585352,hs11:59880847-59880847;hs3:169626703-169626703,hs3:191919640-191919640;hs3:169659126-169659126,hs3:186592620-186592620;hs3:169685756-169685756,hs11:46410714-46410714;hs3:169739113-169739113,hs11:3360077-3360077;hs3:169802670-169802670,hs3:182359849-182359849;hs3:170068602-170068602,hs11:8111256-8111256;hs3:170083369-170083369,hs11:119339220-119339220;hs3:170103016-170103016,hs11:100868418-100868418;hs3:170328874-170328874,hs11:59720045-59720045;hs3:170430862-170430862,hs11:3474708-3474708;hs3:170613022-170613022,hs11:78025935-78025935;hs3:170809878-170809878,hs11:19392758-19392758;hs3:171100372-171100372,hs3:187805941-187805941;hs3:171538876-171538876,hs11:133866937-133866937;hs3:171715007-171715007,hs11:48030721-48030721;hs3:172093772-172093772,hs11:113777698-113777698;hs3:172257204-172257204,hs11:15198424-15198424;hs3:172338347-172338347,hs11:121841215-121841215;hs3:172368195-172368195,hs11:38596103-38596103;hs3:172501609-172501609,hs11:108114116-108114116;hs3:172647660-172647660,hs11:109205841-109205841;hs3:172702198-172702198,hs11:82522890-82522890;hs3:172711841-172711841,hs11:18977082-18977082;hs3:172714956-172714956,hs3:196477485-196477485;hs3:172878301-172878301,hs11:118761588-118761588;hs3:172976295-172976295,hs11:109457161-109457161;hs3:172991596-172991596,hs3:177588443-177588443;hs3:173557432-173557432,hs11:2920499-2920499;hs3:173631935-173631935,hs11:84570264-84570264;hs3:173781550-173781550,hs11:42914818-42914818;hs3:173860376-173860376,hs11:134362712-134362712;hs3:173923276-173923276,hs11:105331932-105331932;hs3:173939108-173939108,hs3:192487685-192487685;hs3:173977562-173977562,hs11:104629397-104629397;hs3:174039023-174039023,hs11:63632590-63632590;hs3:174107746-174107746,hs11:108151237-108151237;hs3:174368081-174368081,hs11:113104300-113104300;hs3:174697566-174697566,hs11:62937616-62937616;hs3:174730757-174730757,hs11:3200713-3200713;hs3:174777207-174777207,hs11:130687075-130687075;hs3:174847166-174847166,hs11:125367389-125367389;hs3:174891577-174891577,hs11:87338591-87338591;hs3:174918005-174918005,hs11:62151345-62151345;hs3:175048744-175048744,hs11:122212189-122212189;hs3:175096150-175096150,hs11:68574257-68574257;hs3:175142500-175142500,hs11:16410898-16410898;hs3:175152277-175152277,hs11:86206132-86206132;hs3:175519741-175519741,hs11:132175119-132175119;hs3:175558126-175558126,hs3:183037909-183037909;hs3:175762780-175762780,hs11:46137941-46137941;hs3:175832424-175832424,hs11:94849056-94849056;hs3:176132948-176132948,hs11:56282322-56282322;hs3:176192696-176192696,hs3:180593432-180593432;hs3:176227708-176227708,hs11:100963532-100963532;hs3:176258767-176258767,hs11:35159982-35159982;hs3:176449438-176449438,hs11:105900515-105900515;hs3:176648664-176648664,hs11:84701817-84701817;hs3:176666740-176666740,hs11:37983847-37983847;hs3:176676871-176676871,hs11:109365673-109365673;hs3:176776929-176776929,hs11:80287720-80287720;hs3:176886492-176886492,hs11:100141459-100141459;hs3:176993197-176993197,hs11:109656139-109656139;hs3:176993906-176993906,hs11:20685254-20685254;hs3:177072172-177072172,hs11:25757475-25757475;hs3:177096146-177096146,hs11:63114919-63114919;hs3:177099270-177099270,hs11:4840090-4840090;hs3:177104263-177104263,hs11:88894991-88894991;hs3:177147333-177147333,hs11:10943543-10943543;hs3:177476782-177476782,hs11:101410203-101410203;hs3:177492452-177492452,hs11:63948787-63948787;hs3:177565441-177565441,hs11:9519864-9519864;hs3:177621565-177621565,hs3:190858522-190858522;hs3:177721984-177721984,hs11:49307899-49307899;hs3:177866830-177866830,hs11:95310963-95310963;hs3:177893213-177893213,hs11:84143560-84143560;hs3:177931876-177931876,hs11:63479710-63479710;hs3:178115633-178115633,hs11:3364515-3364515;hs3:178136868-178136868,hs3:181565832-181565832;hs3:178394800-178394800,hs11:43456068-43456068;hs3:178595454-178595454,hs11:86141701-86141701;hs3:178626306-178626306,hs11:57411089-57411089;hs3:178637772-178637772,hs11:90317620-90317620;hs3:179010995-179010995,hs3:195109518-195109518;hs3:179540969-179540969,hs11:63389375-63389375;hs3:179666493-179666493,hs11:38211357-38211357;hs3:179708777-179708777,hs11:40872977-40872977;hs3:179753057-179753057,hs11:37443443-37443443;hs3:179765672-179765672,hs11:133649099-133649099;hs3:179996434-179996434,hs11:17280622-17280622;hs3:180532814-180532814,hs11:4263985-4263985;hs3:180547769-180547769,hs11:21371360-21371360;hs3:180891505-180891505,hs11:128976293-128976293;hs3:181071313-181071313,hs11:14259942-14259942;hs3:181093810-181093810,hs11:115456038-115456038;hs3:181135805-181135805,hs3:189212944-189212944;hs3:181143869-181143869,hs11:6918405-6918405;hs3:181196468-181196468,hs11:122605199-122605199;hs3:181498633-181498633,hs11:21406311-21406311;hs3:181599778-181599778,hs11:117999439-117999439;hs3:181607157-181607157,hs11:15925465-15925465;hs3:181610346-181610346,hs11:84804620-84804620;hs3:181746618-181746618,hs11:60881256-60881256;hs3:181810201-181810201,hs11:125262253-125262253;hs3:181840305-181840305,hs11:8178433-8178433;hs3:181908487-181908487,hs3:194013069-194013069;hs3:182079262-182079262,hs11:706883-706883;hs3:182161969-182161969,hs11:115545096-115545096;hs3:182184992-182184992,hs11:39339228-39339228;hs3:182394843-182394843,hs11:60940210-60940210;hs3:182403781-182403781,hs11:98202612-98202612;hs3:182812433-182812433,hs11:89347873-89347873;hs3:182842694-182842694,hs11:116493554-116493554;hs3:183010560-183010560,hs11:121942862-121942862;hs3:183154623-183154623,hs11:68020553-68020553;hs3:183197411-183197411,hs11:16832845-16832845;hs3:183683297-183683297,hs11:28277498-28277498;hs3:183893213-183893213,hs3:185057903-185057903;hs3:183925440-183925440,hs11:2651309-2651309;hs3:184115530-184115530,hs11:59988250-59988250;hs3:184125004-184125004,hs11:17774691-17774691;hs3:184312363-184312363,hs3:197429518-197429518;hs3:184593956-184593956,hs11:62073928-62073928;hs3:184903839-184903839,hs11:66459150-66459150;hs3:184920289-184920289,hs11:117940505-117940505;hs3:184992813-184992813,hs11:95876174-95876174;hs3:185019064-185019064,hs11:2458776-2458776;hs3:185153154-185153154,hs11:121566777-121566777;hs3:185485090-185485090,hs11:93021255-93021255;hs3:185492943-185492943,hs11:101126583-101126583;hs3:185506034-185506034,hs11:59559997-59559997;hs3:185585294-185585294,hs11:41145334-41145334;hs3:185593373-185593373,hs11:117420914-117420914;hs3:185731693-185731693,hs11:58803376-58803376;hs3:185779615-185779615,hs11:133773869-133773869;hs3:185818187-185818187,hs11:102168828-102168828;hs3:185843076-185843076,hs11:63688473-63688473;hs3:185853681-185853681,hs11:36077549-36077549;hs3:185869285-185869285,hs11:131794871-131794871;hs3:185986248-185986248,hs11:64931869-64931869;hs3:186005464-186005464,hs3:189542169-189542169;hs3:186159939-186159939,hs11:33511676-33511676;hs3:186628124-186628124,hs11:39487173-39487173;hs3:186642986-186642986,hs11:15207313-15207313;hs3:186740884-186740884,hs11:92117162-92117162;hs3:186786351-186786351,hs11:3202867-3202867;hs3:187388924-187388924,hs3:193332448-193332448;hs3:187411931-187411931,hs11:80892339-80892339;hs3:187617075-187617075,hs11:59892189-59892189;hs3:187619773-187619773,hs11:98733613-98733613;hs3:187726875-187726875,hs11:97867035-97867035;hs3:187752688-187752688,hs11:43772239-43772239;hs3:187760832-187760832,hs11:45422305-45422305;hs3:187775518-187775518,hs3:195424757-195424757;hs3:187961007-187961007,hs11:100775152-100775152;hs3:188055686-188055686,hs11:132625251-132625251;hs3:188124004-188124004,hs11:65521087-65521087;hs3:188419945-188419945,hs11:39537020-39537020;hs3:188478680-188478680,hs11:28600072-28600072;hs3:188488966-188488966,hs11:126922436-126922436;hs3:188630345-188630345,hs11:96078016-96078016;hs3:188846728-188846728,hs11:61568679-61568679;hs3:188891676-188891676,hs11:34925892-34925892;hs3:188974041-188974041,hs11:115437412-115437412;hs3:188981829-188981829,hs11:118661887-118661887;hs3:189398440-189398440,hs11:11325733-11325733;hs3:189585513-189585513,hs11:32449111-32449111;hs3:189730753-189730753,hs3:194605359-194605359;hs3:189850480-189850480,hs11:126240863-126240863;hs3:189913490-189913490,hs11:36499765-36499765;hs3:190189730-190189730,hs11:86121145-86121145;hs3:190207310-190207310,hs11:3172998-3172998;hs3:190580678-190580678,hs11:12834336-12834336;hs3:190845863-190845863,hs11:107617889-107617889;hs3:190972878-190972878,hs11:4725016-4725016;hs3:191036674-191036674,hs11:105124759-105124759;hs3:191047424-191047424,hs11:32835045-32835045;hs3:191096841-191096841,hs11:87628894-87628894;hs3:191278980-191278980,hs11:58455967-58455967;hs3:191368975-191368975,hs11:22668959-22668959;hs3:191466783-191466783,hs11:103658047-103658047;hs3:191469758-191469758,hs11:28099985-28099985;hs3:191586302-191586302,hs11:43542138-43542138;hs3:191649389-191649389,hs11:89840300-89840300;hs3:192098022-192098022,hs11:9619238-9619238;hs3:192104761-192104761,hs11:88713978-88713978;hs3:192137735-192137735,hs11:67811772-67811772;hs3:192163638-192163638,hs11:65351437-65351437;hs3:192348193-192348193,hs11:19558454-19558454;hs3:192382736-192382736,hs11:120017022-120017022;hs3:192443582-192443582,hs11:29083478-29083478;hs3:192552243-192552243,hs3:194063917-194063917;hs3:192852746-192852746,hs11:55942001-55942001;hs3:192932284-192932284,hs11:9706538-9706538;hs3:192934234-192934234,hs3:193150146-193150146;hs3:193006752-193006752,hs11:33874066-33874066;hs3:193048152-193048152,hs11:66516442-66516442;hs3:193155163-193155163,hs11:28855061-28855061;hs3:193177888-193177888,hs11:97016073-97016073;hs3:193253008-193253008,hs11:95679912-95679912;hs3:193381239-193381239,hs11:118002404-118002404;hs3:193542053-193542053,hs11:133732832-133732832;hs3:194005903-194005903,hs11:122788075-122788075;hs3:194068175-194068175,hs11:97160019-97160019;hs3:194180519-194180519,hs11:78013689-78013689;hs3:194300818-194300818,hs11:38160994-38160994;hs3:194643160-194643160,hs11:90852517-90852517;hs3:194756214-194756214,hs11:10315989-10315989;hs3:194805034-194805034,hs11:120529360-120529360;hs3:195000630-195000630,hs11:13680948-13680948;hs3:195041729-195041729,hs11:88718332-88718332;hs3:195079801-195079801,hs11:46953140-46953140;hs3:195124478-195124478,hs11:68095785-68095785;hs3:195272220-195272220,hs11:31532812-31532812;hs3:195606789-195606789,hs11:110078516-110078516;hs3:195899183-195899183,hs11:10565045-10565045;hs3:196137592-196137592,hs11:2438439-2438439;hs3:196156276-196156276,hs11:76907780-76907780;hs3:196289257-196289257,hs11:115089392-115089392;hs3:196317110-196317110,hs11:57324195-57324195;hs3:196340521-196340521,hs11:43465749-43465749;hs3:196385510-196385510,hs11:42626970-42626970;hs3:196464638-196464638,hs11:6163412-6163412;hs3:196663342-196663342,hs11:98784398-98784398;hs3:196770537-196770537,hs11:87189586-87189586;hs3:196810574-196810574,hs11:28808190-28808190;hs3:196819414-196819414,hs11:98701898-98701898;hs3:196972237-196972237,hs11:46132596-46132596;hs3:197121502-197121502,hs11:120216147-120216147;hs3:197594076-197594076,hs11:1445785-1445785;hs3:197667209-197667209,hs11:19507785-19507785;hs3:197729088-197729088,hs11:113550691-113550691;hs3:197768855-197768855,hs11:10573378-10573378;hs3:197768856-197768856,hs11:10573377-10573377;hs3:197900117-197900117,hs11:102309516-102309516;hs4:41719417-41719417,hs8:130652019-130652019;hs4:49513183-49513183,hs11:60249413-60249413;hs4:49558494-49558494,hs11:45855692-45855692;hs4:49562940-49562940,hs11:55127162-55127162;hs5:164233798-164233798,hs5:164234737-164234737;hs7:81048454-81048454,hs11:33261794-33261794;hs7:151932983-151932983,hs11:5730768-5730768;hs7:152074268-152074268,hs11:87228443-87228443;hs10:53978547-53978547,hs10:53988250-53988250;hs10:118722884-118722884,hsX:34242453-34242453;hs11:268913-268913,hs11:5965452-5965452;hs11:330081-330081,hs11:57021420-57021420;hs11:392247-392247,hs11:36127177-36127177;hs11:507215-507215,hs11:60539636-60539636;hs11:562781-562781,hs11:60581145-60581145;hs11:638763-638763,hs11:125306014-125306014;hs11:676761-676761,hs11:66024737-66024737;hs11:733522-733522,hs11:62883589-62883589;hs11:786071-786071,hs11:64807223-64807223;hs11:793171-793171,hs11:125586341-125586341;hs11:1078151-1078151,hs11:66667842-66667842;hs11:1279061-1279061,hs11:126640246-126640246;hs11:1289493-1289493,hs11:47574726-47574726;hs11:1293686-1293686,hs11:32695959-32695959;hs11:1343695-1343695,hs11:57969118-57969118;hs11:1529516-1529516,hs11:9825833-9825833;hs11:1565801-1565801,hs11:107619199-107619199;hs11:1584725-1584725,hs11:69064275-69064275;hs11:1786242-1786242,hs11:99968427-99968427;hs11:1877812-1877812,hs11:7097029-7097029;hs11:1967919-1967919,hs11:123964751-123964751;hs11:1981324-1981324,hs11:68170813-68170813;hs11:2323420-2323420,hs11:67291757-67291757;hs11:2325890-2325890,hs11:2327145-2327145;hs11:2331485-2331485,hs11:116249779-116249779;hs11:2338433-2338433,hs11:123971182-123971182;hs11:2589010-2589010,hs11:99235781-99235781;hs11:2605983-2605983,hs11:28279238-28279238;hs11:2680048-2680048,hs11:40574188-40574188;hs11:2775034-2775034,hs11:96442366-96442366;hs11:2993305-2993305,hs11:112318346-112318346;hs11:3060838-3060838,hs11:7277544-7277544;hs11:3137810-3137810,hs11:121941303-121941303;hs11:3149720-3149720,hs11:11357855-11357855;hs11:3164642-3164642,hs11:6976088-6976088;hs11:3232066-3232066,hs11:49423516-49423516;hs11:3249958-3249958,hs11:80086081-80086081;hs11:3393662-3393662,hs11:12597831-12597831;hs11:3832722-3832722,hs11:113984070-113984070;hs11:3895372-3895372,hs11:80028034-80028034;hs11:4282061-4282061,hs11:82599111-82599111;hs11:4476225-4476225,hs11:68708936-68708936;hs11:4523478-4523478,hs11:108729522-108729522;hs11:4628446-4628446,hs11:63478021-63478021;hs11:4632851-4632851,hs11:113293833-113293833;hs11:4636849-4636849,hs11:44175874-44175874;hs11:4720665-4720665,hs11:94517230-94517230;hs11:4735753-4735753,hs21:10972421-10972421;hs11:4798218-4798218,hs11:51523788-51523788;hs11:4804304-4804304,hs11:106999511-106999511;hs11:4853729-4853729,hs11:92394974-92394974;hs11:4970857-4970857,hs21:10598292-10598292;hs11:5152184-5152184,hs11:111537614-111537614;hs11:5326142-5326142,hs11:25066155-25066155;hs11:5357275-5357275,hs11:118699989-118699989;hs11:5396999-5396999,hs11:42483656-42483656;hs11:5441685-5441685,hs11:15368146-15368146;hs11:5452271-5452271,hs11:16837521-16837521;hs11:5541917-5541917,hs11:127445552-127445552;hs11:5542196-5542196,hs11:107148092-107148092;hs11:5565548-5565548,hs11:115757473-115757473;hs11:5747684-5747684,hs11:130480105-130480105;hs11:6434837-6434837,hs11:111850136-111850136;hs11:6444924-6444924,hs11:115754905-115754905;hs11:6456390-6456390,hs11:22263854-22263854;hs11:6634951-6634951,hs11:48469282-48469282;hs11:6721648-6721648,hs11:48719849-48719849;hs11:6815403-6815403,hs11:125484895-125484895;hs11:6840244-6840244,hs11:47869983-47869983;hs11:6851255-6851255,hs11:100891810-100891810;hs11:6852549-6852549,hs11:94736712-94736712;hs11:6860815-6860815,hs11:81466319-81466319;hs11:6936796-6936796,hs11:63504659-63504659;hs11:7097793-7097793,hs11:60427195-60427195;hs11:7330062-7330062,hs11:129886616-129886616;hs11:7372595-7372595,hs11:35014334-35014334;hs11:7379063-7379063,hs11:124091418-124091418;hs11:7571804-7571804,hs11:38308932-38308932;hs11:7603495-7603495,hs11:107770881-107770881;hs11:7647548-7647548,hs11:100147072-100147072;hs11:7806685-7806685,hs11:61620066-61620066;hs11:8001847-8001847,hs11:93957122-93957122;hs11:8223613-8223613,hs11:95138072-95138072;hs11:8341146-8341146,hs11:110445489-110445489;hs11:8464457-8464457,hs11:87927827-87927827;hs11:8712112-8712112,hs11:127416913-127416913;hs11:9127364-9127364,hs11:59823491-59823491;hs11:9224285-9224285,hs11:125688139-125688139;hs11:9431209-9431209,hs11:93591330-93591330;hs11:9459818-9459818,hs21:9663974-9663974;hs11:9624455-9624455,hs11:92119591-92119591;hs11:9627801-9627801,hs11:132160740-132160740;hs11:9837835-9837835,hs11:120168330-120168330;hs11:9918722-9918722,hs11:94787190-94787190;hs11:10146807-10146807,hs11:93569205-93569205;hs11:10355124-10355124,hs11:20916868-20916868;hs11:10658718-10658718,hs11:30878577-30878577;hs11:10675874-10675874,hs11:17305513-17305513;hs11:10813598-10813598,hs11:45581685-45581685;hs11:10852036-10852036,hs11:83327016-83327016;hs11:11193334-11193334,hs11:25988074-25988074;hs11:11242944-11242944,hs11:30079468-30079468;hs11:11269022-11269022,hs11:79526065-79526065;hs11:11458362-11458362,hs11:34535650-34535650;hs11:11662662-11662662,hs11:118946997-118946997;hs11:11777004-11777004,hs11:36912767-36912767;hs11:11842442-11842442,hs11:130191482-130191482;hs11:11871512-11871512,hs11:16466953-16466953;hs11:12273489-12273489,hs11:111155506-111155506;hs11:12291819-12291819,hs11:55562055-55562055;hs11:12293998-12293998,hs11:110956186-110956186;hs11:12310017-12310017,hs11:98960190-98960190;hs11:12507814-12507814,hs11:94224356-94224356;hs11:12760598-12760598,hs11:37918755-37918755;hs11:12882669-12882669,hs11:118278729-118278729;hs11:13104077-13104077,hs11:102109864-102109864;hs11:13319396-13319396,hs11:116018850-116018850;hs11:13348769-13348769,hs11:29841055-29841055;hs11:13442301-13442301,hs11:68562633-68562633;hs11:13590553-13590553,hs11:21309242-21309242;hs11:13607486-13607486,hs11:91041375-91041375;hs11:14013843-14013843,hs11:80183202-80183202;hs11:14026411-14026411,hs11:50766053-50766053;hs11:14187783-14187783,hs11:56239485-56239485;hs11:14348921-14348921,hs11:130027596-130027596;hs11:14421844-14421844,hs11:50703975-50703975;hs11:14426542-14426542,hs11:61203825-61203825;hs11:14777932-14777932,hs11:87780047-87780047;hs11:14785553-14785553,hs11:55799771-55799771;hs11:14825739-14825739,hs11:132231113-132231113;hs11:15090652-15090652,hs11:57952723-57952723;hs11:15126833-15126833,hs11:85832317-85832317;hs11:15151014-15151014,hs11:78923614-78923614;hs11:15266164-15266164,hs11:105872909-105872909;hs11:15543324-15543324,hs11:121228946-121228946;hs11:15633551-15633551,hs11:80703825-80703825;hs11:15715517-15715517,hs11:46954108-46954108;hs11:15773902-15773902,hs11:43702493-43702493;hs11:15856880-15856880,hs11:27765123-27765123;hs11:15974425-15974425,hs11:85108362-85108362;hs11:15983959-15983959,hs11:46416992-46416992;hs11:16235542-16235542,hs11:24225675-24225675;hs11:16365737-16365737,hs11:29944151-29944151;hs11:16486131-16486131,hs11:43380525-43380525;hs11:16585885-16585885,hs11:84369346-84369346;hs11:16663188-16663188,hs11:129507539-129507539;hs11:16785932-16785932,hs11:40577771-40577771;hs11:16895266-16895266,hs11:31289289-31289289;hs11:17088543-17088543,hs11:83241772-83241772;hs11:17234169-17234169,hs11:79665103-79665103;hs11:17240899-17240899,hs11:98293945-98293945;hs11:17277044-17277044,hs11:92539641-92539641;hs11:17440814-17440814,hs11:111531045-111531045;hs11:18019997-18019997,hs11:101227853-101227853;hs11:18472887-18472887,hs11:83853717-83853717;hs11:18637170-18637170,hs11:111942795-111942795;hs11:19131208-19131208,hs11:80627173-80627173;hs11:19211452-19211452,hs11:64119842-64119842;hs11:19218047-19218047,hs11:56530905-56530905;hs11:19906753-19906753,hs11:100917235-100917235;hs11:20020036-20020036,hs11:28795757-28795757;hs11:20140673-20140673,hs11:89315091-89315091;hs11:20274059-20274059,hs11:31877955-31877955;hs11:20283256-20283256,hs11:28912666-28912666;hs11:20456276-20456276,hs11:42140808-42140808;hs11:20595270-20595270,hs11:124785321-124785321;hs11:20629501-20629501,hs11:82311645-82311645;hs11:20707626-20707626,hs11:110940854-110940854;hs11:20769894-20769894,hs11:122542064-122542064;hs11:20971271-20971271,hs11:90267461-90267461;hs11:21010885-21010885,hs11:32618417-32618417;hs11:21153374-21153374,hs11:44538008-44538008;hs11:21377033-21377033,hs11:34870919-34870919;hs11:21884319-21884319,hs11:127022115-127022115;hs11:21915434-21915434,hs11:25494420-25494420;hs11:22145995-22145995,hs11:35161445-35161445;hs11:22247366-22247366,hs11:128486591-128486591;hs11:22506840-22506840,hs11:29077476-29077476;hs11:22608544-22608544,hs11:36318665-36318665;hs11:22861760-22861760,hs11:39194848-39194848;hs11:23411838-23411838,hs11:63663041-63663041;hs11:23610488-23610488,hs11:103786277-103786277;hs11:23619261-23619261,hs11:25626950-25626950;hs11:23620228-23620228,hs11:119529956-119529956;hs11:23623440-23623440,hs11:82526918-82526918;hs11:23771998-23771998,hs11:99610986-99610986;hs11:23831819-23831819,hs11:92415012-92415012;hs11:23869006-23869006,hs11:35110411-35110411;hs11:23875139-23875139,hs11:35256636-35256636;hs11:24120979-24120979,hs11:115722477-115722477;hs11:24493575-24493575,hs11:28916815-28916815;hs11:24533530-24533530,hs11:33080981-33080981;hs11:24667488-24667488,hs11:29416612-29416612;hs11:24692267-24692267,hs11:77879199-77879199;hs11:24697532-24697532,hs11:43955409-43955409;hs11:24704367-24704367,hs11:50246796-50246796;hs11:24770982-24770982,hs11:25290625-25290625;hs11:24893495-24893495,hs11:91495915-91495915;hs11:25077881-25077881,hs11:37149709-37149709;hs11:25147920-25147920,hs11:86433109-86433109;hs11:25180757-25180757,hs11:84751902-84751902;hs11:25214855-25214855,hs11:82519525-82519525;hs11:25253395-25253395,hs11:38622851-38622851;hs11:25362861-25362861,hs11:45510543-45510543;hs11:25529130-25529130,hs11:129567316-129567316;hs11:25763107-25763107,hs11:27748241-27748241;hs11:25766324-25766324,hs11:99260875-99260875;hs11:25845760-25845760,hs11:67844035-67844035;hs11:25883601-25883601,hs11:124473881-124473881;hs11:25918303-25918303,hs11:93831756-93831756;hs11:25925394-25925394,hs11:130478664-130478664;hs11:25967999-25967999,hs11:124066251-124066251;hs11:26279745-26279745,hs11:37561284-37561284;hs11:26608492-26608492,hs11:134025799-134025799;hs11:26947461-26947461,hs11:79718016-79718016;hs11:27265204-27265204,hs11:50009740-50009740;hs11:27329167-27329167,hs11:84047671-84047671;hs11:27465296-27465296,hs11:66343141-66343141;hs11:27471684-27471684,hs11:132801495-132801495;hs11:27583350-27583350,hs11:50764708-50764708;hs11:27608082-27608082,hs11:63405080-63405080;hs11:27856533-27856533,hs11:44821693-44821693;hs11:28026586-28026586,hs11:115136939-115136939;hs11:28058373-28058373,hs11:42026718-42026718;hs11:28313835-28313835,hs11:120506010-120506010;hs11:29262378-29262378,hs11:118072614-118072614;hs11:29752385-29752385,hs11:96266765-96266765;hs11:30082976-30082976,hs11:80075753-80075753;hs11:30186947-30186947,hs11:77237744-77237744;hs11:30333449-30333449,hs11:92438727-92438727;hs11:30737169-30737169,hs11:123061280-123061280;hs11:30876066-30876066,hs11:132648047-132648047;hs11:31251194-31251194,hs11:33861169-33861169;hs11:31326855-31326855,hs11:107769431-107769431;hs11:31606851-31606851,hs11:43042410-43042410;hs11:31629768-31629768,hs11:37661428-37661428;hs11:31714551-31714551,hs11:42855424-42855424;hs11:31780439-31780439,hs11:63013938-63013938;hs11:31781491-31781491,hs11:108176470-108176470;hs11:31832177-31832177,hs11:77115283-77115283;hs11:32498496-32498496,hs11:99679369-99679369;hs11:32680037-32680037,hs11:43095667-43095667;hs11:32887194-32887194,hs11:130195972-130195972;hs11:32893714-32893714,hs11:81145278-81145278;hs11:33342209-33342209,hs11:48337027-48337027;hs11:33743463-33743463,hs11:120170834-120170834;hs11:33803075-33803075,hs11:109416916-109416916;hs11:33947607-33947607,hs11:131979279-131979279;hs11:33976469-33976469,hs11:120524824-120524824;hs11:34073495-34073495,hs11:77087340-77087340;hs11:34187340-34187340,hs11:105156177-105156177;hs11:34194649-34194649,hs11:63121707-63121707;hs11:34314524-34314524,hs11:46422957-46422957;hs11:34928531-34928531,hs11:65398376-65398376;hs11:35069693-35069693,hs11:132172427-132172427;hs11:35273095-35273095,hs11:82971059-82971059;hs11:35383828-35383828,hs11:67293140-67293140;hs11:35405298-35405298,hs11:42687251-42687251;hs11:35757349-35757349,hs11:131761235-131761235;hs11:35880939-35880939,hs11:87996198-87996198;hs11:36177330-36177330,hs11:94014579-94014579;hs11:36236584-36236584,hs11:84575995-84575995;hs11:36670381-36670381,hs11:106939255-106939255;hs11:36918418-36918418,hs11:94944382-94944382;hs11:37222622-37222622,hs11:117188922-117188922;hs11:37241962-37241962,hs11:37636116-37636116;hs11:37489609-37489609,hs21:10985388-10985388;hs11:37677114-37677114,hs11:82163637-82163637;hs11:38132522-38132522,hs11:44607562-44607562;hs11:38140588-38140588,hs11:134368194-134368194;hs11:38190995-38190995,hs11:39210521-39210521;hs11:38206849-38206849,hs11:56642432-56642432;hs11:38288192-38288192,hs11:99198512-99198512;hs11:38791473-38791473,hs11:80016587-80016587;hs11:39184727-39184727,hs11:102990848-102990848;hs11:39210364-39210364,hs11:107013946-107013946;hs11:39266952-39266952,hs11:93778289-93778289;hs11:39344121-39344121,hs11:41065913-41065913;hs11:40584055-40584055,hs11:79580603-79580603;hs11:40644422-40644422,hs11:87456520-87456520;hs11:40742012-40742012,hs11:123895335-123895335;hs11:41533087-41533087,hs11:118667501-118667501;hs11:41809790-41809790,hs11:41883115-41883115;hs11:41845194-41845194,hs11:104601413-104601413;hs11:41901840-41901840,hs11:78567102-78567102;hs11:42013270-42013270,hs11:65047775-65047775;hs11:42062034-42062034,hs11:92118761-92118761;hs11:42062299-42062299,hs11:113153746-113153746;hs11:42082625-42082625,hs11:95108291-95108291;hs11:42103883-42103883,hs11:120360677-120360677;hs11:42425913-42425913,hs11:90103032-90103032;hs11:42588666-42588666,hs11:108855441-108855441;hs11:42828388-42828388,hs11:51492327-51492327;hs11:43096497-43096497,hs11:107205251-107205251;hs11:43306735-43306735,hs11:134286123-134286123;hs11:43860989-43860989,hs11:76903317-76903317;hs11:43934083-43934083,hs11:67815607-67815607;hs11:44403838-44403838,hs11:65581002-65581002;hs11:44600852-44600852,hs11:117200461-117200461;hs11:44784654-44784654,hs11:109695951-109695951;hs11:44975746-44975746,hs11:125042051-125042051;hs11:45220821-45220821,hs11:113678795-113678795;hs11:45402943-45402943,hs11:134723748-134723748;hs11:45412688-45412688,hs11:102562641-102562641;hs11:45459884-45459884,hs11:62842935-62842935;hs11:45466815-45466815,hs11:99977309-99977309;hs11:45512828-45512828,hs11:119372638-119372638;hs11:45558291-45558291,hs11:106895188-106895188;hs11:46739499-46739499,hs11:103809371-103809371;hs11:46796046-46796046,hs11:110142626-110142626;hs11:47200784-47200784,hs11:86215207-86215207;hs11:47530011-47530011,hs11:87824744-87824744;hs11:47578480-47578480,hs11:125055195-125055195;hs11:47599917-47599917,hs11:94779202-94779202;hs11:47621746-47621746,hs11:49501557-49501557;hs11:47622864-47622864,hs11:104719278-104719278;hs11:47632392-47632392,hs11:108286609-108286609;hs11:48015227-48015227,hs11:80472874-80472874;hs11:48067271-48067271,hs11:80436373-80436373;hs11:48462094-48462094,hs11:84057819-84057819;hs11:48558703-48558703,hs11:132705345-132705345;hs11:48708533-48708533,hs11:62305815-62305815;hs11:48819122-48819122,hs11:111334751-111334751;hs11:49581298-49581298,hs11:131621156-131621156;hs11:49652473-49652473,hs11:56525252-56525252;hs11:50028057-50028057,hs11:87384734-87384734;hs11:50097754-50097754,hs11:104937564-104937564;hs11:50182970-50182970,hs11:81581669-81581669;hs11:50238662-50238662,hs11:130020765-130020765;hs11:50433159-50433159,hs11:59667411-59667411;hs11:50511488-50511488,hs11:105320747-105320747;hs11:51299642-51299642,hs11:124476499-124476499;hs11:51521306-51521306,hs11:128478405-128478405;hs11:54959876-54959876,hs11:67017661-67017661;hs11:54961337-54961337,hs11:65914141-65914141;hs11:55168636-55168636,hs11:123481278-123481278;hs11:55334165-55334165,hs11:122853607-122853607;hs11:55576982-55576982,hs11:93810967-93810967;hs11:55716545-55716545,hs11:111158995-111158995;hs11:55743285-55743285,hs11:90324006-90324006;hs11:55834916-55834916,hs11:78426973-78426973;hs11:56248665-56248665,hs11:66868368-66868368;hs11:56354512-56354512,hs11:112891707-112891707;hs11:56409866-56409866,hs11:118883667-118883667;hs11:56422679-56422679,hs11:100796895-100796895;hs11:56471995-56471995,hs11:121116798-121116798;hs11:56657656-56657656,hs21:10603614-10603614;hs11:56671781-56671781,hs11:81998847-81998847;hs11:56690797-56690797,hs11:79520842-79520842;hs11:56709395-56709395,hs11:127262495-127262495;hs11:57119361-57119361,hs11:124347063-124347063;hs11:57271436-57271436,hs11:107202216-107202216;hs11:57339431-57339431,hs11:118595140-118595140;hs11:58769148-58769148,hs11:61292314-61292314;hs11:58772914-58772914,hs11:94612977-94612977;hs11:58804978-58804978,hs11:127635984-127635984;hs11:59404355-59404355,hs11:61887332-61887332;hs11:59566583-59566583,hs11:94984466-94984466;hs11:59620260-59620260,hs11:121488358-121488358;hs11:59819948-59819948,hs11:118515758-118515758;hs11:60237063-60237063,hs11:122395034-122395034;hs11:60780141-60780141,hs11:79811368-79811368;hs11:60870134-60870134,hs11:95861050-95861050;hs11:60881062-60881062,hs11:89111545-89111545;hs11:60964757-60964757,hs11:112889414-112889414;hs11:61381381-61381381,hs11:115054506-115054506;hs11:61502883-61502883,hs11:104614402-104614402;hs11:61543903-61543903,hs11:68530300-68530300;hs11:61591649-61591649,hs11:106706920-106706920;hs11:61688917-61688917,hs11:121087866-121087866;hs11:61767987-61767987,hs11:100393099-100393099;hs11:61782370-61782370,hs11:105030547-105030547;hs11:61886050-61886050,hs11:94890296-94890296;hs11:61986956-61986956,hs11:91073913-91073913;hs11:62100282-62100282,hs11:68682343-68682343;hs11:62232474-62232474,hs11:78081956-78081956;hs11:62308309-62308309,hs11:98290076-98290076;hs11:62577529-62577529,hs11:133790977-133790977;hs11:62613765-62613765,hs11:114040217-114040217;hs11:63032638-63032638,hs11:107576150-107576150;hs11:63168736-63168736,hs11:100195130-100195130;hs11:63367698-63367698,hs11:117331120-117331120;hs11:63406701-63406701,hs11:107368265-107368265;hs11:64082368-64082368,hs11:132833249-132833249;hs11:64106063-64106063,hs11:131118091-131118091;hs11:64390217-64390217,hs11:65687191-65687191;hs11:64849695-64849695,hs11:95796717-95796717;hs11:64892357-64892357,hs11:65140343-65140343;hs11:64974544-64974544,hs11:81117066-81117066;hs11:65162942-65162942,hs11:77594479-77594479;hs11:65493637-65493637,hs11:85772683-85772683;hs11:65766422-65766422,hs11:116932804-116932804;hs11:65980785-65980785,hs11:124830949-124830949;hs11:66035083-66035083,hs11:112345043-112345043;hs11:66180577-66180577,hs11:123543114-123543114;hs11:66401205-66401205,hs11:133825492-133825492;hs11:67004296-67004296,hs11:68577666-68577666;hs11:67172445-67172445,hs11:121501133-121501133;hs11:67871676-67871676,hs11:118011877-118011877;hs11:68050803-68050803,hs11:111812062-111812062;hs11:68196637-68196637,hs11:127418074-127418074;hs11:68310573-68310573,hs11:111310374-111310374;hs11:68317875-68317875,hs11:113778860-113778860;hs11:69010572-69010572,hs11:83695950-83695950;hs11:76801614-76801614,hs11:132330384-132330384;hs11:77015750-77015750,hs11:94652988-94652988;hs11:77122508-77122508,hs11:92495103-92495103;hs11:77353675-77353675,hs11:100930422-100930422;hs11:77463541-77463541,hs11:133730172-133730172;hs11:77736200-77736200,hs11:91918890-91918890;hs11:78179585-78179585,hs11:78489569-78489569;hs11:78800056-78800056,hs11:101337756-101337756;hs11:78966659-78966659,hs11:94480213-94480213;hs11:79040184-79040184,hs11:85833302-85833302;hs11:79222719-79222719,hs11:102813632-102813632;hs11:79396998-79396998,hs11:105787164-105787164;hs11:79419342-79419342,hs11:111832925-111832925;hs11:79463936-79463936,hs11:98763191-98763191;hs11:79613713-79613713,hs11:118873529-118873529;hs11:79702962-79702962,hs11:81157602-81157602;hs11:80139145-80139145,hs11:90647427-90647427;hs11:80233126-80233126,hs11:88691559-88691559;hs11:80605463-80605463,hs11:104451127-104451127;hs11:80904121-80904121,hs11:119776463-119776463;hs11:81181611-81181611,hs11:119339755-119339755;hs11:81192867-81192867,hs11:101812872-101812872;hs11:81265583-81265583,hs11:86327999-86327999;hs11:81750323-81750323,hs11:110494413-110494413;hs11:82063253-82063253,hs11:110660175-110660175;hs11:82153430-82153430,hs11:87815197-87815197;hs11:82184200-82184200,hs11:130702510-130702510;hs11:82404794-82404794,hs11:113296300-113296300;hs11:83363512-83363512,hs11:111163229-111163229;hs11:83605854-83605854,hs11:90203528-90203528;hs11:83699589-83699589,hs11:100543274-100543274;hs11:83916631-83916631,hs11:86648781-86648781;hs11:84002863-84002863,hs11:134653221-134653221;hs11:84669295-84669295,hs11:125417055-125417055;hs11:85914954-85914954,hs11:92406126-92406126;hs11:87184184-87184184,hs11:106566955-106566955;hs11:87387629-87387629,hs11:130545128-130545128;hs11:87475388-87475388,hs11:92063589-92063589;hs11:87759726-87759726,hs11:106494437-106494437;hs11:87898916-87898916,hs11:99004096-99004096;hs11:88229057-88229057,hs11:107656219-107656219;hs11:88575070-88575070,hs11:102930019-102930019;hs11:89003575-89003575,hs11:117335437-117335437;hs11:89837850-89837850,hs11:115974214-115974214;hs11:90019665-90019665,hs11:113146230-113146230;hs11:90190500-90190500,hs11:119913147-119913147;hs11:90721141-90721141,hs11:99532562-99532562;hs11:90823061-90823061,hs11:131227344-131227344;hs11:91123606-91123606,hs11:111509495-111509495;hs11:92066081-92066081,hs11:95737606-95737606;hs11:92966962-92966962,hs11:125066695-125066695;hs11:93043127-93043127,hs11:132996998-132996998;hs11:93474506-93474506,hs11:95558272-95558272;hs11:93505246-93505246,hs11:117690320-117690320;hs11:94519917-94519917,hs11:101147249-101147249;hs11:94832980-94832980,hs11:108076264-108076264;hs11:94998965-94998965,hs11:108957334-108957334;hs11:95243896-95243896,hs11:115737086-115737086;hs11:95758432-95758432,hs11:97554517-97554517;hs11:95759614-95759614,hs11:111227338-111227338;hs11:95845552-95845552,hs11:106736117-106736117;hs11:96186162-96186162,hs11:105585145-105585145;hs11:96458661-96458661,hs11:132721776-132721776;hs11:96667880-96667880,hs11:96733291-96733291;hs11:96720351-96720351,hs11:111524857-111524857;hs11:97336621-97336621,hs11:101103545-101103545;hs11:97717552-97717552,hs11:100541534-100541534;hs11:97910892-97910892,hs11:115629376-115629376;hs11:98524026-98524026,hs11:106280902-106280902;hs11:98667845-98667845,hs11:125562659-125562659;hs11:98781209-98781209,hs11:131427074-131427074;hs11:99259879-99259879,hs11:131209011-131209011;hs11:99355369-99355369,hs11:105303490-105303490;hs11:99530651-99530651,hs11:113062216-113062216;hs11:99617194-99617194,hs11:133979142-133979142;hs11:99733916-99733916,hs11:99735108-99735108;hs11:99901815-99901815,hs11:126608396-126608396;hs11:99929410-99929410,hs11:118814725-118814725;hs11:101068710-101068710,hs11:128968564-128968564;hs11:101318861-101318861,hs11:102824454-102824454;hs11:101343073-101343073,hs11:104662270-104662270;hs11:101406564-101406564,hs11:129669213-129669213;hs11:101558263-101558263,hs11:127599347-127599347;hs11:101558580-101558580,hs11:130090019-130090019;hs11:101818627-101818627,hs11:126126545-126126545;hs11:101826699-101826699,hs11:112560956-112560956;hs11:103011271-103011271,hs11:121459213-121459213;hs11:104155864-104155864,hs11:108395685-108395685;hs11:104190027-104190027,hs11:122201198-122201198;hs11:104517355-104517355,hs11:126770283-126770283;hs11:104659107-104659107,hs11:124883086-124883086;hs11:105530427-105530427,hs11:114937254-114937254;hs11:105910540-105910540,hs11:115476025-115476025;hs11:106554360-106554360,hs11:121449226-121449226;hs11:106899019-106899019,hs11:129339637-129339637;hs11:107376218-107376218,hs11:126604022-126604022;hs11:108511919-108511919,hs11:116215150-116215150;hs11:109220708-109220708,hs11:111230212-111230212;hs11:110250858-110250858,hs11:117137157-117137157;hs11:111380755-111380755,hs11:129374682-129374682;hs11:111915251-111915251,hs11:127568029-127568029;hs11:112020423-112020423,hs11:125954805-125954805;hs11:112077192-112077192,hs11:126238013-126238013;hs11:112922753-112922753,hs11:119186434-119186434;hs11:113001809-113001809,hs11:134315320-134315320;hs11:113476193-113476193,hs11:134847984-134847984;hs11:114648072-114648072,hs11:131131661-131131661;hs11:114723892-114723892,hs11:129506023-129506023;hs11:114732952-114732952,hs11:125027469-125027469;hs11:115746469-115746469,hs11:121245576-121245576;hs11:116052663-116052663,hs11:126057747-126057747;hs11:116212755-116212755,hs11:119071634-119071634;hs11:116261911-116261911,hs11:119105456-119105456;hs11:116295415-116295415,hs11:126636053-126636053;hs11:118009020-118009020,hs11:122086577-122086577;hs11:118403855-118403855,hs11:133665894-133665894;hs11:118403856-118403856,hs11:133665894-133665894;hs11:119065985-119065985,hs11:129855008-129855008;hs11:122399606-122399606,hs11:123891501-123891501;hs11:122768923-122768923,hs11:133073476-133073476;hs11:123515157-123515157,hs11:132418934-132418934;hs11:124548254-124548254,hs21:9591834-9591834;hs11:125806689-125806689,hs11:128133673-128133673;hs11:126013467-126013467,hs11:134943537-134943537;hs11:126852514-126852514,hs11:128905331-128905331;hs11:128982637-128982637,hs11:133677455-133677455;hs14:53778126-53778126,hs15:95055625-95055625 We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73DeltaEx2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer. GRCh37/hg19 ABI3BP,CAT;ABTB2,CNTN5;ABTB2,TPCN2;ACER3,DLG2;ACOX2,PTDSS2;ACPP,KLHL24;ADAMTS9,FXR1;ADCY5,CPB1;ADCY5,DYNC2H1;ALCAM,FCHSD2;ALDH1L1,FGF12;ANKRD28,NELL1;ANO10,NEK11;ANO10,PIK3CA;ARHGAP31,PLEKHA7;ARHGEF26,CPT1A;ARHGEF26,DKK3;ARHGEF3,AP2M1;ARHGEF3,CAPRIN1;ARHGEF3,GTF2H1;ARHGEF3,MB21D2;ARHGEF3,TOPBP1;ARID1A,TECTA;ARIH2,PACS1;ARL8B,LRRC2;ARL8B,PTPRJ;ARNTL,SIK3;ATG3,CPSF7;ATP1B3,FXYD2;ATP2C1,PTPRJ;B4GALT4,FOXRED1;BBX,PLEKHA7;BSN,RNF13;BTD,PLD1;C11orf49,EML3;C11orf49,PRCP;C11orf80,KIAA1731;C11orf80,MAML2;C3orf20,LMLN;C3orf26,ARAP1;C3orf26,ARNTL;C3orf26,IFT80;C3orf26,SLC17A6;C3orf26;FILIP1L,GPR156;C3orf37,TOPBP1;C3orf67,C11orf30;C3orf67,DLG2;CACNA1D,ACP2;CACNA1D,ARHGAP32;CACNA1D,C11orf30;CACNA1D,CADPS;CACNA1D,CSTF3;CACNA1D,EEF1G;CACNA2D3,ARHGAP31;CACNA2D3,C3orf26;CACNA2D3,CADM2;CACNA2D3,DLG2;CACNA2D3,DYNC2H1;CACNA2D3,GSTP1;CACNA2D3,HYOU1;CACNA2D3,LDLRAD3;CACNA2D3,MAGI1;CACNA2D3,MAML2;CACNA2D3,NUP98;CACNA2D3,RTN3;CADM2,C11orf73;CADM2,EPHB1;CADM2,PHC3;CADM2,POU2F3;CADM2,PTPRJ;CADM2,RIC3;CADPS,EPHA6;CADPS,MYNN;CADPS,TMEM132A;CADPS,VWCE;CAND2,ATP2C1;CAPN5,INTS4;CAPRIN1,FADS2;CBLB,TMEM126A;CBLB,TMEM135;CBLB,TP63;CCDC37,MGLL;CD6,LRP5;CD86,VSTM5;CELSR3,TOMM70A;CHCHD6,ARHGAP32;CHDH,FAM131A;CHEK1,FAM118B;CLPB,DLG2;CLSTN2,APLP2;CMC1,FHIT;CMTM8,FGF12;CNTN4,ARIH2;CNTN4,MTNR1B;CNTN5,C11orf57;CNTN5,NPAT;CNTN5,ZBTB16;CNTN6,ADAMTS9;CNTN6,EPHA3;CNTN6,SLC12A8;CNTN6,TRIM44;COL6A6,NELL1;COLQ,PLXNB1;CPNE4,DDB2;CPNE4,PACS1;CPNE4,POLA2;CSRP3,EEF1G;CTSW,DSCAML1;CTSW,OPCML;DDX10,OPCML;DEAF1,PVRL1;DGKG,ALX4;DIRC2,RNF214;DLG1,TNFRSF21;DLG2,AMOTL1;DNAH1,LSAMP;DNAH1,PTDSS2;DNHD1,LTBP3;DOCK3,CLSTN2;DOCK3,FAM43A;DOCK3,MPPED2;DOCK3,PARP15;DOCK3,PLD1;DOCK3,PLEKHA7;DOCK3,TFDP2;DOCK3,VPS8;DRD3,ROPN1;DSCAML1,NTM;ECT2,C11orf30;EDEM1,MACROD1;EEFSEC,CHKA;EIF4E3,TECTA;EIF4E3,TMEM108;ELP4,ABTB2;EPHA3,TNIK;EPHA3,VEPH1;EPHA6,SOX6;EPHA6,ZW10;EPHB1,ALG8;EPHB1,KIRREL3;EPHB1,SLC1A2;EPHB1,TP63;ERC2,ACY3;ERC2,CADPS;ERC2,GPR156;ERC2,HSD17B12;ERC2,LDLRAD3;ERC2,LUZP2;ERC2,MYLK;ERC2,NELL1;ERC2,PAMR1;ETV5,TEAD1;EXOSC7,CADPS;FAM107A,ALG8;FAM19A1,CSTF3;FAM19A1,PGAP2;FAM19A4,KCNMB2;FAM19A4,RNF13;FANCD2,TSEN2;FBLN2,LRP5;FBXL2,LPP;FBXL2,PARL;FHIT,AMBRA1;FHIT,FXR1;FHIT,GAB2;FLNB,CLPB;FLNB,OPCML;FLNB,SLC43A1;FRMD4B,ALCAM;FRMD4B,ROBO2;FXYD2,POU2F3;FYCO1,ZDHHC5;FYCO1,ZNF148;GADL1,F2;GALNTL4,CCDC73;GALNTL4,CPT1A;GAS2,FAM118B;GBE1,C3orf26;GOLGA4,CACNA1D;GOLGA4,TRAK1;GPR128,ATP13A5;GPR128,CNTN5;GPR128,DLG1;GPR156,TNIK;GRM2,GNB4;GRM7,MFN1;GRM7,POLQ;GRM7,PXK;GRM7,TMEM135;GSK3B,DLG2;GSK3B,TEAD1;HACL1,LMLN;HEG1,STIM1;HHATL,NAV2;HPS3,NOX4;HRASLS5,DDX10;HSD17B12,KIRREL3;IFT122,ABTB2;IFT122,DLG2;IGF2BP2,AP2A2;IGSF11,NLGN1;IL20RA,GRM1;IQCJ,MPPED2;IQSEC1,PVRL1;ITGA9,EPHA6;ITIH1,USP13;ITPR1,PLEKHB1;KALRN,DLG2;KALRN,FADS2;KALRN,GNB4;KALRN,SLC9A9;KAT2B,CADPS;KCNH8,C11orf70;KCNH8,CTR9;KCNH8,FHIT;KCNH8,MYLK;KCNH8,RAB6A;KCNH8,RNF13;KCNH8,SBF2;KCNH8,SLC9A9;KCNQ1,PVRL1;KDM2A,GLB1L2;KIF15,CACNA2D3;KIF9,MAGI1;KIF9,TMEM9B;KLHL18,NEK11;KLHL6,OPCML;KY,APLP2;LAMA2,ODZ1;LARS2,CHMP2B;LARS2,LPP;LDHA,APLP2;LDLRAD3,NTM;LHFPL4,SHISA5;LPP,GALNTL4;LPP,LGR4;LRIG1,SUV420H1;LRIG1,TRA2B;LRP5,MAML2;LRRC2,LEPREL1;LRRC34,NARS2;LRRFIP2,KCNQ1;LSAMP,POLA2;MAGI1,EHBP1L1;MAGI1,IGHMBP2;MAGI1,RNF121;MAGI1,SLC3A2;MAP4,MB21D2;MARK2,DCPS;MCM2,LGR4;MINA,MAP3K11;MITF,MCF2L2;MLF1,ARAP1;MLL,JAM3;MME,DLG2;MYRIP,EPHA6;NAA50,NAV2;NAALADL2,EXT2;NAALADL2,ZNF214;NAV2,CSTF3;NAV2,TTC17;NELL1,NPAT;NELL1,PDGFD;NISCH,PRDM11;NLGN1,CDC42BPG;NLGN1,HSD17B12;NLGN1,SYT9;NLGN1,VPS8;NMD3,USP28;NR1I2,PDE3B;NRXN2,KIRREL3;NRXN2,VPS26B;NUP210,DLG2;NUP210,FBXO3;OGG1,PLEKHA7;OPA1,DLG2;OSBPL10,EIF4G2;OSBPL10,ULK4;OXSR1,RAB6A;P4HTM,PANX1;PACS1,SESN3;PAK2,ELP4;PARVA,BTBD10;PBRM1,CCDC67;PBRM1,PPFIA1;PDDC1,SNX19;PDIA5,MAML2;PDIA5,NDUFB5;PDZRN3,MED12L;PDZRN3,ROBO2;PDZRN3,TBL1XR1;PEX5L,MAML2;PHC3,MACROD1;PHF21A,MAML2;PHF21A,NRXN2;PIK3CB,NAALADL2;PIK3CB,PANX1;PIK3R4,PAK2;PLCD1,CORO1B;PLCH1,PACS1;PLCXD2,NAALADL2;PLEKHA7,PHLDB1;POLR2L,CFL1;PRDM11,MTA2;PRKAR2A,MYH15;PRKAR2A,NAALADL2;PRKAR2A,TMEM135;PRKRIR,PGR;PRMT3,NTM;PRRG4,TM7SF2;PRSS42,CD86;PSMC3,MYO7A;PTPLB,ALDH1L1;PTPLB,POU2F3;PTPRG,ABI3BP;PTPRG,ARRB1;PTPRG,CLPB;PTPRG,EXT2;PTPRG,PARP15;PTPRG,SDHAF2;PTPRG,SLC25A26;PTPRG,TNIK;PTPRJ,DAGLA;PTPRJ,GRIA4;RAB43,SIK3;RAB6B,AP2A2;RAB6B,TEAD1;RASA2,CDHR5;RASA2,LDLRAD3;RBM6,CPA3;RBM6,GUCY1A2;RFTN1,UBP1;RHOA,PPFIA1;RIC3,OPCML;RNF13,APLP2;RNF13,POLA2;RNF169,ZBTB16;ROBO1,TSPAN18;ROBO2,CADM1;ROBO2,CD200R1;ROBO2,DLG2;ROBO2,FAM118B;ROBO2,MAML2;ROBO2,NSUN3;ROBO2,PGM2L1;ROBO2,PLS1;ROBO2,SIDT1;ROBO2,ZBTB16;RSRC1,C11orf49;RSRC1,NELL1;SACM1L,DLG2;SACM1L,PTPRG;SBF2,LRP4;SBF2,NAV2;SCN10A,NARS2;SCN11A,AHNAK;SCN11A,PRDM11;SCN5A,TNK2;SEC22A,NRIP3;SEC61A1,LPP;SEMA3G,PTPLB;SETD2,AHNAK;SETD2,ATP11B;SETD2,SKIL;SETD5,STXBP5L;SIGIRR,SLCO2B1;SIRT3,DSCAML1;SLC12A8,CKAP5;SLC1A2,GRIK4;SLC22A25,C11orf85;SLC25A26,ZW10;SLC33A1,DLG2;SLC3A2,ARHGAP32;SLC3A2,PVRL1;SLC43A1,NTM;SLC4A7,CPNE4;SLC6A11,DSCAML1;SLC6A11,NAV2;SLC9A9,CCDC50;SLC9A9,LDLRAD3;SLCO2A1,SBF2;SLMAP,CPNE4;SLMAP,PARP15;SMARCC1,TFDP2;SPATA16,DLG2;SRGAP3,EPHA3;SRGAP3,SOX6;ST6GAL1,GRM1;ST6GAL1,IL20RA;STAB1,TNIK;STAC,FLNB;STARD10,PKNOX2;STIM1,DLG2;STT3B,CCDC81;STT3B,MAP3K11;STT3B,MYRIP;STXBP5L,GANAB;STXBP5L,IQCJ;STXBP5L,RDX;STXBP5L,VPS8;SUCLG2,MS4A4A;SUMF1,GRIA4;SUMF1,ITIH1;SUMF1,KCNAB1;SUMF1,LMLN;TBC1D5,VPS8;TEAD1,PTPRJ;TGFBR2,AP2A2;TGFBR2,TNK2;THRB,NLGN1;TMEM108,APOC3;TMEM216,BSCL2;TMEM89,SLC22A18;TNIK,DSCAML1;TNIK,LDLRAD3;TOMM70A,DLG2;TOPBP1,NTM;TP63,GRM5;TRANK1,CPNE4;TRANK1,EPHA3;TRANK1,FRMD4B;TRANK1,GRIK4;TRIM44,RDX;TSEN2,NAALADL2;TSPAN18,C11orf49;TSPAN4,SIDT2;U2SURP,SHOX2;UBE2E1,TMEM135;UBE2E2,STXBP5L;ULK4,SIRT3;UMPS,MAML2;VPS8,DLG2;VSTM5,ACSL4;VWA5B2,KIRREL3;WDR53,MPPED2;WDR74,FAM55B;WNT7A,VSTM5;XXYLT1,PGAP2;XXYLT1,TEAD1;ZBTB11,ILDR1;ZDHHC13,KIRREL3;ZMAT3,LUZP2;ZNF148,AHNAK;ZNF589,LSAMP;ZNF589,SLMAP CTDB0434 Methodology 26415501 Mardin BR, Drainas AP, Waszak SM, Weischenfeldt J, Isokane M, Stutz AM, Raeder B, Efthymiopoulos T, Buccitelli C, Segura-Wang M, Northcott P, Pfister SM, Lichter P, Ellenberg J, Korbel JO A cell-based model system links chromothripsis with hyperploidy Molecular Systems Biology 2015 Sep 12,22 hTERT RPE-1 cell line Next Generation Sequencing Homo sapiens BM178 Illumina HiSeq 2000, MiSeq or NextSeq RASSF3;RASSF9 European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed complex alterations after selection and transformation (CAST), enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular in hyperploid cells. Analysis of primary medulloblastoma cancer genomes verified the link between hyperploidy and chromothripsis in vivo. CAST provides the foundation for mechanistic dissection of complex DNA rearrangement processes. GRCh37/hg19 PRJEB8037 No NA CTDB0435 Methodology 26415501 Mardin BR, Drainas AP, Waszak SM, Weischenfeldt J, Isokane M, Stutz AM, Raeder B, Efthymiopoulos T, Buccitelli C, Segura-Wang M, Northcott P, Pfister SM, Lichter P, Ellenberg J, Korbel JO A cell-based model system links chromothripsis with hyperploidy Molecular Systems Biology 2015 Sep 8,15 hTERT RPE-1 cell line Next Generation Sequencing Homo sapiens BM175 Illumina HiSeq 2000, MiSeq or NextSeq BUBR1;CASC5 European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed complex alterations after selection and transformation (CAST), enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular in hyperploid cells. Analysis of primary medulloblastoma cancer genomes verified the link between hyperploidy and chromothripsis in vivo. CAST provides the foundation for mechanistic dissection of complex DNA rearrangement processes. GRCh37/hg19 PRJEB8037 No NA CTDB0436 Methodology 26415501 Mardin BR, Drainas AP, Waszak SM, Weischenfeldt J, Isokane M, Stutz AM, Raeder B, Efthymiopoulos T, Buccitelli C, Segura-Wang M, Northcott P, Pfister SM, Lichter P, Ellenberg J, Korbel JO A cell-based model system links chromothripsis with hyperploidy Molecular Systems Biology 2015 Sep 12 hTERT RPE-1 cell line Next Generation Sequencing Homo sapiens BM237 Illumina HiSeq 2000, MiSeq or NextSeq European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed complex alterations after selection and transformation (CAST), enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular in hyperploid cells. Analysis of primary medulloblastoma cancer genomes verified the link between hyperploidy and chromothripsis in vivo. CAST provides the foundation for mechanistic dissection of complex DNA rearrangement processes. GRCh37/hg19 PRJEB8037 No NA CTDB0437 Methodology 26415501 Mardin BR, Drainas AP, Waszak SM, Weischenfeldt J, Isokane M, Stutz AM, Raeder B, Efthymiopoulos T, Buccitelli C, Segura-Wang M, Northcott P, Pfister SM, Lichter P, Ellenberg J, Korbel JO A cell-based model system links chromothripsis with hyperploidy Molecular Systems Biology 2015 Sep 14 medulloblastoma Next Generation Sequencing Homo sapiens MB34 European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed complex alterations after selection and transformation (CAST), enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular in hyperploid cells. Analysis of primary medulloblastoma cancer genomes verified the link between hyperploidy and chromothripsis in vivo. CAST provides the foundation for mechanistic dissection of complex DNA rearrangement processes. GRCh37/hg19 Yes NA CTDB0438 Methodology 26415501 Mardin BR, Drainas AP, Waszak SM, Weischenfeldt J, Isokane M, Stutz AM, Raeder B, Efthymiopoulos T, Buccitelli C, Segura-Wang M, Northcott P, Pfister SM, Lichter P, Ellenberg J, Korbel JO A cell-based model system links chromothripsis with hyperploidy Molecular Systems Biology 2015 Sep 15 medulloblastoma Next Generation Sequencing Homo sapiens MB243 European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed complex alterations after selection and transformation (CAST), enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular in hyperploid cells. Analysis of primary medulloblastoma cancer genomes verified the link between hyperploidy and chromothripsis in vivo. CAST provides the foundation for mechanistic dissection of complex DNA rearrangement processes. GRCh37/hg19 Yes NA CTDB0439 Methodology 26415501 Mardin BR, Drainas AP, Waszak SM, Weischenfeldt J, Isokane M, Stutz AM, Raeder B, Efthymiopoulos T, Buccitelli C, Segura-Wang M, Northcott P, Pfister SM, Lichter P, Ellenberg J, Korbel JO A cell-based model system links chromothripsis with hyperploidy Molecular Systems Biology 2015 Sep 14 hTERT RPE-1 cell line Next Generation Sequencing Homo sapiens BM694 Illumina HiSeq 2000, MiSeq or NextSeq European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed complex alterations after selection and transformation (CAST), enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular in hyperploid cells. Analysis of primary medulloblastoma cancer genomes verified the link between hyperploidy and chromothripsis in vivo. CAST provides the foundation for mechanistic dissection of complex DNA rearrangement processes. GRCh37/hg19 PRJEB8037 No NA CTDB0440 Methodology 26415501 Mardin BR, Drainas AP, Waszak SM, Weischenfeldt J, Isokane M, Stutz AM, Raeder B, Efthymiopoulos T, Buccitelli C, Segura-Wang M, Northcott P, Pfister SM, Lichter P, Ellenberg J, Korbel JO A cell-based model system links chromothripsis with hyperploidy Molecular Systems Biology 2015 Sep 17 hTERT RPE-1 cell line Next Generation Sequencing Homo sapiens BM173 Illumina HiSeq 2000, MiSeq or NextSeq European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed complex alterations after selection and transformation (CAST), enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular in hyperploid cells. Analysis of primary medulloblastoma cancer genomes verified the link between hyperploidy and chromothripsis in vivo. CAST provides the foundation for mechanistic dissection of complex DNA rearrangement processes. GRCh37/hg19 PRJEB8037 No NA CTDB0441 Methodology 26415501 Mardin BR, Drainas AP, Waszak SM, Weischenfeldt J, Isokane M, Stutz AM, Raeder B, Efthymiopoulos T, Buccitelli C, Segura-Wang M, Northcott P, Pfister SM, Lichter P, Ellenberg J, Korbel JO A cell-based model system links chromothripsis with hyperploidy Molecular Systems Biology 2015 Sep 10,X hTERT RPE-1 cell line Next Generation Sequencing Homo sapiens BM1142 Illumina HiSeq 2000, MiSeq or NextSeq European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed complex alterations after selection and transformation (CAST), enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular in hyperploid cells. Analysis of primary medulloblastoma cancer genomes verified the link between hyperploidy and chromothripsis in vivo. CAST provides the foundation for mechanistic dissection of complex DNA rearrangement processes. GRCh37/hg19 PRJEB8037 No NA CTDB0442 Methodology 26415501 Mardin BR, Drainas AP, Waszak SM, Weischenfeldt J, Isokane M, Stutz AM, Raeder B, Efthymiopoulos T, Buccitelli C, Segura-Wang M, Northcott P, Pfister SM, Lichter P, Ellenberg J, Korbel JO A cell-based model system links chromothripsis with hyperploidy Molecular Systems Biology 2015 Sep 6 hTERT RPE-1 cell line Next Generation Sequencing Homo sapiens BM780 Illumina HiSeq 2000, MiSeq or NextSeq European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed complex alterations after selection and transformation (CAST), enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular in hyperploid cells. Analysis of primary medulloblastoma cancer genomes verified the link between hyperploidy and chromothripsis in vivo. CAST provides the foundation for mechanistic dissection of complex DNA rearrangement processes. GRCh37/hg19 PRJEB8037 No NA CTDB0443 Methodology 26415501 Mardin BR, Drainas AP, Waszak SM, Weischenfeldt J, Isokane M, Stutz AM, Raeder B, Efthymiopoulos T, Buccitelli C, Segura-Wang M, Northcott P, Pfister SM, Lichter P, Ellenberg J, Korbel JO A cell-based model system links chromothripsis with hyperploidy Molecular Systems Biology 2015 Sep 6 hTERT RPE-1 cell line Next Generation Sequencing Homo sapiens BM605 Illumina HiSeq 2000, MiSeq or NextSeq European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed complex alterations after selection and transformation (CAST), enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular in hyperploid cells. Analysis of primary medulloblastoma cancer genomes verified the link between hyperploidy and chromothripsis in vivo. CAST provides the foundation for mechanistic dissection of complex DNA rearrangement processes. GRCh37/hg19 PRJEB8037 No NA CTDB0444 Research 26328271 Furgason JM, Koncar RF, Michelhaugh SK, Sarkar FH, Mittal S, Sloan AE, Barnholtz-Sloan JS, Bahassi el M Whole genome sequence analysis links chromothripsis to EGFR, MDM2, MDM4, and CDK4 amplification in glioblastoma Oncoscience 2015 Jul 6,7,12 Glioblastoma Next Generation Sequencing Homo sapiens TCGA-06-0686 MDM2;CDK4;VEGFA Department of Internal Medicine, Division of Hematology/Oncology and UC Brain Tumor Center, University of Cincinnati, Cincinnati OH, USA BACKGROUND: Findings based on recent advances in next-generation sequence analysis suggest that, in some tumors, a single catastrophic event, termed chromothripsis, results in several simultaneous tumorigenic alterations. Previous studies have suggested that glioblastoma (GBM) may exhibit chromothripsis at a higher rate (39%) than other tumors (9%). Primary glioblastoma is an aggressive form of brain cancer that typically appears suddenly in older adults. With aggressive treatment, the median survival time is only 15 months. Their acute onset and widespread genomic instability indicates that chromothripsis may play a key role in their initiation and progression. GBMs are often characterized by EGFR amplification, CDKN2A and PTEN deletion, although approximately 20% of GBMs harbor additional amplifications in MDM2 or MDM4 with CDK4. METHODS: We used the chromothripsis prediction tool, Shatterproof, in conjunction with a custom whole genome sequence analysis pipeline in order to generate putative regions of chromothripsis. The data derived from this study was further expanded on using fluorescence in situ hybridization (FISH) analysis and susceptibility studies with colony formation assays. RESULTS: We show that primary GBMs are associated with higher chromothripsis scores and establish a link between chromothripsis and gene amplification of receptor tyrosine kinases (RTKs), as well as modulators of the TP53 and RB1 pathways. CONCLUSIONS: Utilizing a newly introduced bioinformatic tool, we provide evidence that chromothripsis is associated with the formation of amplicons containing several oncogenes involved in key pathways that are likely essential for post-chromothriptic cell survival. Yes NA CTDB0445 Research 26328271 Furgason JM, Koncar RF, Michelhaugh SK, Sarkar FH, Mittal S, Sloan AE, Barnholtz-Sloan JS, Bahassi el M Whole genome sequence analysis links chromothripsis to EGFR, MDM2, MDM4, and CDK4 amplification in glioblastoma Oncoscience 2015 Jul 1,4,12 Glioblastoma Next Generation Sequencing Homo sapiens TCGA-02-2485 CDK4;PDGFRA Department of Internal Medicine, Division of Hematology/Oncology and UC Brain Tumor Center, University of Cincinnati, Cincinnati OH, USA BACKGROUND: Findings based on recent advances in next-generation sequence analysis suggest that, in some tumors, a single catastrophic event, termed chromothripsis, results in several simultaneous tumorigenic alterations. Previous studies have suggested that glioblastoma (GBM) may exhibit chromothripsis at a higher rate (39%) than other tumors (9%). Primary glioblastoma is an aggressive form of brain cancer that typically appears suddenly in older adults. With aggressive treatment, the median survival time is only 15 months. Their acute onset and widespread genomic instability indicates that chromothripsis may play a key role in their initiation and progression. GBMs are often characterized by EGFR amplification, CDKN2A and PTEN deletion, although approximately 20% of GBMs harbor additional amplifications in MDM2 or MDM4 with CDK4. METHODS: We used the chromothripsis prediction tool, Shatterproof, in conjunction with a custom whole genome sequence analysis pipeline in order to generate putative regions of chromothripsis. The data derived from this study was further expanded on using fluorescence in situ hybridization (FISH) analysis and susceptibility studies with colony formation assays. RESULTS: We show that primary GBMs are associated with higher chromothripsis scores and establish a link between chromothripsis and gene amplification of receptor tyrosine kinases (RTKs), as well as modulators of the TP53 and RB1 pathways. CONCLUSIONS: Utilizing a newly introduced bioinformatic tool, we provide evidence that chromothripsis is associated with the formation of amplicons containing several oncogenes involved in key pathways that are likely essential for post-chromothriptic cell survival. Yes NA CTDB0446 Research 26328271 Furgason JM, Koncar RF, Michelhaugh SK, Sarkar FH, Mittal S, Sloan AE, Barnholtz-Sloan JS, Bahassi el M Whole genome sequence analysis links chromothripsis to EGFR, MDM2, MDM4, and CDK4 amplification in glioblastoma Oncoscience 2015 Jul 7,12 Glioblastoma Next Generation Sequencing Homo sapiens TCGA-19-2624 EGFR;MDM2;CDK4 Department of Internal Medicine, Division of Hematology/Oncology and UC Brain Tumor Center, University of Cincinnati, Cincinnati OH, USA BACKGROUND: Findings based on recent advances in next-generation sequence analysis suggest that, in some tumors, a single catastrophic event, termed chromothripsis, results in several simultaneous tumorigenic alterations. Previous studies have suggested that glioblastoma (GBM) may exhibit chromothripsis at a higher rate (39%) than other tumors (9%). Primary glioblastoma is an aggressive form of brain cancer that typically appears suddenly in older adults. With aggressive treatment, the median survival time is only 15 months. Their acute onset and widespread genomic instability indicates that chromothripsis may play a key role in their initiation and progression. GBMs are often characterized by EGFR amplification, CDKN2A and PTEN deletion, although approximately 20% of GBMs harbor additional amplifications in MDM2 or MDM4 with CDK4. METHODS: We used the chromothripsis prediction tool, Shatterproof, in conjunction with a custom whole genome sequence analysis pipeline in order to generate putative regions of chromothripsis. The data derived from this study was further expanded on using fluorescence in situ hybridization (FISH) analysis and susceptibility studies with colony formation assays. RESULTS: We show that primary GBMs are associated with higher chromothripsis scores and establish a link between chromothripsis and gene amplification of receptor tyrosine kinases (RTKs), as well as modulators of the TP53 and RB1 pathways. CONCLUSIONS: Utilizing a newly introduced bioinformatic tool, we provide evidence that chromothripsis is associated with the formation of amplicons containing several oncogenes involved in key pathways that are likely essential for post-chromothriptic cell survival. Yes NA CTDB0448 Research 26993771 Schutze DM, Krijgsman O, Snijders PJ, Ylstra B, Weischenfeldt J, Mardin BR, Stutz AM, Korbel JO, de Winter JP, Meijer CJ, Quint WG, Bosch L, Wilting SM, Steenbergen RD Immortalization capacity of HPV types is inversely related to chromosomal instability Oncotarget 2016 Mar 8 HPV transducted human foreskin keratinocytes cell line Next Generation Sequencing Homo sapiens donorI_HPV16_passage40 Illumina HiSeq MYC Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands High-risk human papillomavirus (hrHPV) types induce immortalization of primary human epithelial cells. Previously we demonstrated that immortalization of human foreskin keratinocytes (HFKs) is HPV type dependent, as reflected by the presence or absence of a crisis period before reaching immortality. This study determined how the immortalization capacity of ten hrHPV types relates to DNA damage induction and overall genomic instability in HFKs.Twenty five cell cultures obtained by transduction of ten hrHPV types (i.e. HPV16/18/31/33/35/45/51/59/66/70 E6E7) in two or three HFK donors each were studied.All hrHPV-transduced HFKs showed an increased number of double strand DNA breaks compared to controls, without exhibiting significant differences between types. However, immortal descendants of HPV-transduced HFKs that underwent a prior crisis period (HPV45/51/59/66/70-transduced HFKs) showed significantly more chromosomal aberrations compared to those without crisis (HPV16/18/31/33/35-transduced HFKs). Notably, the hTERT locus at 5p was exclusively gained in cells with a history of crisis and coincided with increased expression. Chromothripsis was detected in one cell line in which multiple rearrangements within chromosome 8 resulted in a gain of MYC.Together we demonstrated that upon HPV-induced immortalization, the number of chromosomal aberrations is inversely related to the viral immortalization capacity. We propose that hrHPV types with reduced immortalization capacity in vitro, reflected by a crisis period, require more genetic host cell aberrations to facilitate immortalization than types that can immortalize without crisis. This may in part explain the observed differences in HPV-type prevalence in cervical cancers and emphasizes that changes in the host cell genome contribute to HPV-induced carcinogenesis. PRJEB9176 No NA CTDB0450 Research 26929209 Nazaryan-Petersen L, Bertelsen B, Bak M, Jonson L, Tommerup N, Hancks DC, Tumer Z Germline Chromothripsis Driven by L1-Mediated Retrotransposition and Alu/Alu Homologous Recombination Hum Mutat 2016 Apr 3,5 Congenital abnormality Next Generation Sequencing Homo sapiens 26929209_1 Illumina HiSeq 2500 Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Glostrup, 2600, Denmark Chromothripsis (CTH) is a phenomenon where multiple localized double-stranded DNA breaks result in complex genomic rearrangements. Although the DNA-repair mechanisms involved in CTH have been described, the mechanisms driving the localized "shattering" process remain unclear. High-throughput sequence analysis of a familial germline CTH revealed an inserted SVAE retrotransposon associated with a 110-kb deletion displaying hallmarks of L1-mediated retrotransposition. Our analysis suggests that the SVAE insertion did not occur prior to or after, but concurrent with the CTH event. We also observed L1-endonuclease potential target sites in other breakpoints. In addition, we found four Alu elements flanking the 110-kb deletion and associated with an inversion. We suggest that chromatin looping mediated by homologous Alu elements may have brought distal DNA regions into close proximity facilitating DNA cleavage by catalytically active L1-endonuclease. Our data provide the first evidence that active and inactive human retrotransposons can serve as endogenous mutagens driving CTH in the germline. GRCh37/hg19 No NA CTDB0458 Research 26862731 Morishita M, Muramatsu T, Suto Y, Hirai M, Konishi T, Hayashi S, Shigemizu D, Tsunoda T, Moriyama K, Inazawa J Chromothripsis-like chromosomal rearrangements induced by ionizing radiation using proton microbeam irradiation system Oncotarget 2016 Mar 2,5,7,20 Irradiated oral squamous cell carcinoma cell line Next Generation Sequencing Homo sapiens LM200-#25 Illumina HiSeq2500 chr2:0-16112058:0;chr2:16112059-16374530:1;chr2:16374531-48874200:0;chr2:48874201-83960470:1;chr2:83960471-243199373:0;chr5:0-60181451:0;chr5:180693129-180915260:0;chr5:60181452-95997250:-1;chr5:95997251-96133484:0;chr5:96133485-180693128:-1;chr7:0-26267810:0;chr7:117737888-127700972:0;chr7:127700973-159119487:-1;chr7:159119488-159138663:0;chr7:26267811-56070567:-1;chr7:56070568-90400491:0;chr7:90400492-91667757:-1;chr7:91667758-93403512:0;chr7:93403513-117737887:-1 hs1:71158954-71158954,hs7:62926589-62926589;hs1:188668262-188668262,hs7:97211292-97211292;hs2:15742427-15742427,hs2:16708647-16708647;hs2:48744071-48744071,hs2:48747466-48747466;hs2:48937460-48937460,hs2:81807493-81807493;hs2:53106376-53106376,hs2:53252067-53252067;hs2:56565085-56565085,hs2:56567839-56567839;hs2:65827048-65827048,hs22:35021325-35021325;hs2:76773545-76773545,hs2:76775446-76775446;hs2:80900266-80900266,hs2:80902393-80902393;hs2:163267921-163267921,hs13:21026190-21026190;hs2:184164179-184164179,hs6:53249177-53249177;hs2:219807376-219807376,hs12:55980975-55980975;hs3:51204229-51204229,hs7:136312283-136312283;hs3:151238360-151238360,hs5:101050301-101050301;hs5:6330715-6330715,hs5:6378446-6378446;hs5:12037575-12037575,hsX:54658517-54658517;hs5:12734098-12734098,hs5:12772396-12772396;hs5:17285317-17285317,hs15:34587946-34587946;hs5:19854136-19854136,hs5:89613574-89613574;hs5:26699124-26699124,hsX:70598444-70598444;hs5:35097012-35097012,hs5:35100018-35100018;hs5:39026838-39026838,hs5:39028538-39028538;hs5:75087709-75087709,hs5:75098716-75098716;hs5:89613939-89613939,hs20:14453979-14453979;hs5:95994648-95994648,hs5:96157386-96157386;hs5:117106928-117106928,hs11:98419831-98419831;hs5:130420471-130420471,hs15:24577473-24577473;hs7:26274040-26274040,hs7:123601514-123601514;hs7:51228105-51228105,hs7:51281767-51281767;hs7:54282791-54282791,hs15:48978914-48978914;hs7:61968855-61968855,hs8:43607720-43607720;hs7:62252943-62252943,hs9:66855983-66855983;hs7:84778168-84778168,hs7:84780433-84780433;hs7:103591420-103591420,hs7:103594627-103594627;hs7:127757865-127757865,hs7:127820843-127820843;hs7:127757919-127757919,hs11:23404608-23404608;hs7:157089773-157089773,hs7:157091014-157091014;hs9:75394745-75394745,hs20:16772828-16772828;hs12:53845486-53845486,hs20:5707706-5707706;hs20:7144623-7144623,hs20:7157143-7157143;hs20:46422302-46422302,hs20:46423898-46423898;hs20:57562332-57562332,hs20:57708381-57708381 Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan Chromothripsis is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event, rather than an accumulation of a series of subsequent and random alterations. Chromothripsis occurs commonly in various human cancers and is thought to be associated with increased malignancy and carcinogenesis. However, the causes and consequences of chromothripsis remain unclear. Therefore, to identify the mechanism underlying the generation of chromothripsis, we investigated whether chromothripsis could be artificially induced by ionizing radiation. We first elicited DNA double-strand breaks in an oral squamous cell carcinoma cell line HOC313-P and its highly metastatic subline HOC313-LM, using Single Particle Irradiation system to Cell (SPICE), a focused vertical microbeam system designed to irradiate a spot within the nuclei of adhesive cells, and then established irradiated monoclonal sublines from them, respectively. SNP array analysis detected a number of chromosomal copy number alterations (CNAs) in these sublines, and one HOC313-LM-derived monoclonal subline irradiated with 200 protons by the microbeam displayed multiple CNAs involved locally in chromosome 7. Multi-color FISH showed a complex translocation of chromosome 7 involving chromosomes 11 and 12. Furthermore, whole genome sequencing analysis revealed multiple de novo complex chromosomal rearrangements localized in chromosomes 2, 5, 7, and 20, resembling chromothripsis. These findings suggested that localized ionizing irradiation within the nucleus may induce chromothripsis-like complex chromosomal alterations via local DNA damage in the nucleus. GRCh37/hg19 No NA CTDB0459 Research 26856307 Ernst A, Jones DT, Maass KK, Rode A, Deeg KI, Jebaraj BM, Korshunov A, Hovestadt V, Tainsky MA, Pajtler KW, Bender S, Brabetz S, Grobner S, Kool M, Devens F, Edelmann J, Zhang C, Castelo-Branco P, Tabori U, Malkin D, Rippe K, Stilgenbauer S, Pfister SM, Zapatka M, Lichter P Telomere dysfunction and chromothripsis Int J Cancer 2016 Jun 15 Li-Fraumeni syndrome Next Generation Sequencing Homo sapiens LFS MDAH087 p145 Illumina MiSeq Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany Chromothripsis is a recently discovered form of genomic instability, characterized by tens to hundreds of clustered DNA rearrangements resulting from a single dramatic event. Telomere dysfunction has been suggested to play a role in the initiation of this phenomenon, which occurs in a large number of tumor entities. Here, we show that telomere attrition can indeed lead to catastrophic genomic events, and that telomere patterns differ between cells analyzed before and after such genomic catastrophes. Telomere length and telomere stabilization mechanisms diverge between samples with and without chromothripsis in a given tumor subtype. Longitudinal analyses of the evolution of chromothriptic patterns identify either stable patterns between matched primary and relapsed tumors, or loss of the chromothriptic clone in the relapsed specimen. The absence of additional chromothriptic events occurring between the initial tumor and the relapsed tumor sample points to telomere stabilization after the initial chromothriptic event which prevents further shattering of the genome. GRCh37/hg19 Yes NA CTDB0460 Research 26856307 Ernst A, Jones DT, Maass KK, Rode A, Deeg KI, Jebaraj BM, Korshunov A, Hovestadt V, Tainsky MA, Pajtler KW, Bender S, Brabetz S, Grobner S, Kool M, Devens F, Edelmann J, Zhang C, Castelo-Branco P, Tabori U, Malkin D, Rippe K, Stilgenbauer S, Pfister SM, Zapatka M, Lichter P Telomere dysfunction and chromothripsis Int J Cancer 2016 Jun 8 Li-Fraumeni syndrome Next Generation Sequencing Homo sapiens LFS MDAH172 p170 Illumina MiSeq Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany Chromothripsis is a recently discovered form of genomic instability, characterized by tens to hundreds of clustered DNA rearrangements resulting from a single dramatic event. Telomere dysfunction has been suggested to play a role in the initiation of this phenomenon, which occurs in a large number of tumor entities. Here, we show that telomere attrition can indeed lead to catastrophic genomic events, and that telomere patterns differ between cells analyzed before and after such genomic catastrophes. Telomere length and telomere stabilization mechanisms diverge between samples with and without chromothripsis in a given tumor subtype. Longitudinal analyses of the evolution of chromothriptic patterns identify either stable patterns between matched primary and relapsed tumors, or loss of the chromothriptic clone in the relapsed specimen. The absence of additional chromothriptic events occurring between the initial tumor and the relapsed tumor sample points to telomere stabilization after the initial chromothriptic event which prevents further shattering of the genome. GRCh37/hg19 Yes NA CTDB0461 Research 26856307 Ernst A, Jones DT, Maass KK, Rode A, Deeg KI, Jebaraj BM, Korshunov A, Hovestadt V, Tainsky MA, Pajtler KW, Bender S, Brabetz S, Grobner S, Kool M, Devens F, Edelmann J, Zhang C, Castelo-Branco P, Tabori U, Malkin D, Rippe K, Stilgenbauer S, Pfister SM, Zapatka M, Lichter P Telomere dysfunction and chromothripsis Int J Cancer 2016 Jun 1 Li-Fraumeni syndrome Next Generation Sequencing Homo sapiens LFS MDAH174 p84 Illumina MiSeq Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany Chromothripsis is a recently discovered form of genomic instability, characterized by tens to hundreds of clustered DNA rearrangements resulting from a single dramatic event. Telomere dysfunction has been suggested to play a role in the initiation of this phenomenon, which occurs in a large number of tumor entities. Here, we show that telomere attrition can indeed lead to catastrophic genomic events, and that telomere patterns differ between cells analyzed before and after such genomic catastrophes. Telomere length and telomere stabilization mechanisms diverge between samples with and without chromothripsis in a given tumor subtype. Longitudinal analyses of the evolution of chromothriptic patterns identify either stable patterns between matched primary and relapsed tumors, or loss of the chromothriptic clone in the relapsed specimen. The absence of additional chromothriptic events occurring between the initial tumor and the relapsed tumor sample points to telomere stabilization after the initial chromothriptic event which prevents further shattering of the genome. GRCh37/hg19 Yes NA CTDB0462 Research 26856307 Ernst A, Jones DT, Maass KK, Rode A, Deeg KI, Jebaraj BM, Korshunov A, Hovestadt V, Tainsky MA, Pajtler KW, Bender S, Brabetz S, Grobner S, Kool M, Devens F, Edelmann J, Zhang C, Castelo-Branco P, Tabori U, Malkin D, Rippe K, Stilgenbauer S, Pfister SM, Zapatka M, Lichter P Telomere dysfunction and chromothripsis Int J Cancer 2016 Jun 15 Li-Fraumeni syndrome Next Generation Sequencing Homo sapiens LFS MDAH041 p308 Illumina MiSeq Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany Chromothripsis is a recently discovered form of genomic instability, characterized by tens to hundreds of clustered DNA rearrangements resulting from a single dramatic event. Telomere dysfunction has been suggested to play a role in the initiation of this phenomenon, which occurs in a large number of tumor entities. Here, we show that telomere attrition can indeed lead to catastrophic genomic events, and that telomere patterns differ between cells analyzed before and after such genomic catastrophes. Telomere length and telomere stabilization mechanisms diverge between samples with and without chromothripsis in a given tumor subtype. Longitudinal analyses of the evolution of chromothriptic patterns identify either stable patterns between matched primary and relapsed tumors, or loss of the chromothriptic clone in the relapsed specimen. The absence of additional chromothriptic events occurring between the initial tumor and the relapsed tumor sample points to telomere stabilization after the initial chromothriptic event which prevents further shattering of the genome. GRCh37/hg19 Yes NA CTDB0463 Research 26833333 Cheng C, Zhou Y, Li H, Xiong T, Li S, Bi Y, Kong P, Wang F, Cui H, Li Y, Fang X, Yan T, Li Y, Wang J, Yang B, Zhang L, Jia Z, Song B, Hu X, Yang J, Qiu H, Zhang G, Liu J, Xu E, Shi R, Zhang Y, Liu H, He C, Zhao Z, Qian Y, Rong R, Han Z, Zhang Y, Luo W, Wang J, Peng S, Yang X, Li X, Li L, Fang H, Liu X, Ma L, Chen Y, Guo S, Chen X, Xi Y, Li G, Liang J, Yang X, Guo J, Jia J, Li Q, Cheng X, Zhan Q, Cui Y Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma Am J Hum Genet 2016 Feb 3,8,10 Esophageal Squamous Cell Carcinoma Next Generation Sequencing Homo sapiens ESCC-16T chr10:0-18799686:0;chr10:107295464-107524429:-1;chr10:109152318-109161696:1;chr10:129314910-130150677:1;chr10:131665143-131805976:1;chr10:132021472-132043752:1;chr10:132608501-135534747:0;chr10:18799687-132608500:-1;chr10:36567859-37354034:-1;chr10:59338920-113561260:-1;chr10:64152636-85727158:-1;chr10:77889913-119683337:-1;chr10:86894560-87123885:-1;chr10:91938941-116723370:1;chr10:95986188-96920838:-1;chr10:97665896-97713580:-1;chr10:97716486-100342350:1;chr3:0-16233013:0;chr3:101580883-101630647:-1;chr3:101630648-102491180:0;chr3:102491181-102493196:-1;chr3:102493197-102497507:0;chr3:102497508-102498064:-1;chr3:102498065-113357003:0;chr3:113357004-113431917:-1;chr3:113431918-150469539:0;chr3:150469540-150471823:-1;chr3:150471824-195892079:0;chr3:16233014-16916643:-1;chr3:16916078-18001210:-1;chr3:18001211-25114479:0;chr3:195892080-195892363:1;chr3:195892364-198022430:0;chr3:25114480-25525392:1;chr3:25525393-36590902:0;chr3:36590903-63520366:1;chr3:41141612-63517257:-1;chr3:41428504-63288749:-1;chr3:44029942-44156406:-1;chr3:63510324-64078201:1;chr3:64078202-101580882:0;chr8:0-2511118:0;chr8:113632773-113669250:0;chr8:113669251-141013010:-1;chr8:115564476-115632269:-1;chr8:141013011-143600971:0;chr8:143600972-143601425:1;chr8:143601426-146364022:0;chr8:2511119-100010158:1;chr8:2534604-38155351:-1;chr8:3118861-3134815:-1;chr8:38223598-38541430:1;chr8:38328480-113632772:1;chr8:38556565-47790553:-1;chr8:38570827-38613056:-1;chr8:63003083-109359733:-1;chr8:84025443-113629666:-1;chr8:94392450-97126855:1;chr8:97479690-105063301:1 hs10:18799687-18799687,hs10:132608500-132608500;hs10:64152636-64152636,hs10:85727158-85727158;hs10:77889913-77889913,hs10:119683337-119683337;hs10:86894560-86894560,hs10:87123885-87123885;hs10:95986188-95986188,hs10:96920838-96920838;hs10:97665896-97665896,hs10:97713580-97713580;hs3:101580883-101580883,hs3:101630647-101630647;hs3:113357004-113357004,hs3:113431917-113431917;hs8:2534604-2534604,hs8:38155351-38155351;hs8:63003083-63003083,hs8:109359733-109359733;hs8:84025443-84025443,hs8:113629666-113629666;hs8:115564476-115564476,hs8:115632269-115632269;hs10:107295464-107295464,hs10:107524429-107524429;hs3:41428504-41428504,hs3:63288749-63288749;hs3:44029942-44029942,hs3:44156406-44156406;hs3:102491181-102491181,hs3:102493196-102493196;hs3:102497508-102497508,hs3:102498064-102498064;hs3:150469540-150469540,hs3:150471823-150471823;hs8:3118861-3118861,hs8:3134815-3134815;hs10:22788853-22788853,hs10:25446672-25446672;hs10:31335227-31335227,hs10:127456844-127456844;hs10:51114263-51114263,hs10:107644289-107644289;hs10:56257329-56257329,hs10:58800207-58800207;hs10:57931391-57931391,hs10:59669581-59669581;hs10:70162216-70162216,hs10:85727435-85727435;hs3:93655186-93655186,hs3:93656757-93656757;hs8:38528682-38528682,hs8:38545835-38545835;hs8:50553129-50553129,hs8:60712307-60712307;hs8:38186885-38186885,hs8:100009977-100009977;hs10:38408429-38408429,hs10:38409339-38409339;hs10:54735824-54735824,hs10:54740580-54740580;hs10:63494715-63494715,hs10:65127791-65127791;hs8:38327526-38327526,hs8:38365764-38365764;hs8:70871734-70871734,hs8:80980343-80980343;hs3:16916078-18001210,hs13:97656007-114591288;hs3:41141612-63517257,hs13:75527349-80875718;hs10:36567859-37354034,hs10:111273520-113129551;hs8:38570827-38613056,hs8:2525371-38505175;hs8:113669251-141013010,hs8:62349687-113632785;hs8:38556565-47790553,hs8:2516754-38344139;hs10:59338920-113561260,hs10:86796758-97716318;hs3:16233014-16916643,hs3:16233557-16818503;hs10:22610610-22610610,hs11:49907500-49907500;hs10:128157670-128157670,hs4:129909276-129909276;hs10:128157767-128157767,hs2:179505467-179505467;hs10:128158158-128158158,hs12:40431733-40431733;hs10:128158714-128158714,hs8:65121951-65121951;hs3:57460418-57460418,hs6:32459056-32459056;hs8:93409789-93409789,hsY:23951604-23951604 C10orf107;C10orf90;CLVS1;FGFR1;JMJD1C;LETM2;SLC2A13;TRAPPC9;WHSC1L1 Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Department of Pathology, the First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, China Comprehensive identification of somatic structural variations (SVs) and understanding their mutational mechanisms in cancer might contribute to understanding biological differences and help to identify new therapeutic targets. Unfortunately, characterization of complex SVs across the whole genome and the mutational mechanisms underlying esophageal squamous cell carcinoma (ESCC) is largely unclear. To define a comprehensive catalog of somatic SVs, affected target genes, and their underlying mechanisms in ESCC, we re-analyzed whole-genome sequencing (WGS) data from 31 ESCCs using Meerkat algorithm to predict somatic SVs and Patchwork to determine copy-number changes. We found deletions and translocations with NHEJ and alt-EJ signature as the dominant SV types, and 16% of deletions were complex deletions. SVs frequently led to disruption of cancer-associated genes (e.g., CDKN2A and NOTCH1) with different mutational mechanisms. Moreover, chromothripsis, kataegis, and breakage-fusion-bridge (BFB) were identified as contributing to locally mis-arranged chromosomes that occurred in 55% of ESCCs. These genomic catastrophes led to amplification of oncogene through chromothripsis-derived double-minute chromosome formation (e.g., FGFR1 and LETM2) or BFB-affected chromosomes (e.g., CCND1, EGFR, ERBB2, MMPs, and MYC), with approximately 30% of ESCCs harboring BFB-derived CCND1 amplification. Furthermore, analyses of copy-number alterations reveal high frequency of whole-genome duplication (WGD) and recurrent focal amplification of CDCA7 that might act as a potential oncogene in ESCC. Our findings reveal molecular defects such as chromothripsis and BFB in malignant transformation of ESCCs and demonstrate diverse models of SVs-derived target genes in ESCCs. These genome-wide SV profiles and their underlying mechanisms provide preventive, diagnostic, and therapeutic implications for ESCCs. GRCh37/hg19 Yes TRAPPC9,CLVS1;C10orf107,JMJD1C;C10orf90,SLC2A13 CTDB0465 Research 26687355 Maciejowski J, Li Y, Bosco N, Campbell PJ, de Lange T Chromothripsis and Kataegis Induced by Telomere Crisis Cell 2015 Dec 4,13,X Retinal pigment epithelial cell line RPE-1 Next Generation Sequencing Homo sapiens X-25 Illumina X-ten Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA Telomere crisis occurs during tumorigenesis when depletion of the telomere reserve leads to frequent telomere fusions. The resulting dicentric chromosomes have been proposed to drive genome instability. Here, we examine the fate of dicentric human chromosomes in telomere crisis. We observed that dicentric chromosomes invariably persisted through mitosis and developed into 50-200 um chromatin bridges connecting the daughter cells. Before their resolution at 3-20 hr after anaphase, the chromatin bridges induced nuclear envelope rupture in interphase, accumulated the cytoplasmic 3' nuclease TREX1, and developed RPA-coated single stranded (ss) DNA. CRISPR knockouts showed that TREX1 contributed to the generation of the ssDNA and the resolution of the chromatin bridges. Post-crisis clones showed chromothripsis and kataegis, presumably resulting from DNA repair and APOBEC editing of the fragmented chromatin bridge DNA. We propose that chromothripsis in human cancer may arise through TREX1-mediated fragmentation of dicentric chromosomes formed in telomere crisis. GRCh37/hg19 No NA CTDB0466 Research 26687355 Maciejowski J, Li Y, Bosco N, Campbell PJ, de Lange T Chromothripsis and Kataegis Induced by Telomere Crisis Cell 2015 Dec 11,18,20 Retinal pigment epithelial cell line RPE-1 Next Generation Sequencing Homo sapiens X-29 Illumina X-ten Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA Telomere crisis occurs during tumorigenesis when depletion of the telomere reserve leads to frequent telomere fusions. The resulting dicentric chromosomes have been proposed to drive genome instability. Here, we examine the fate of dicentric human chromosomes in telomere crisis. We observed that dicentric chromosomes invariably persisted through mitosis and developed into 50-200 um chromatin bridges connecting the daughter cells. Before their resolution at 3-20 hr after anaphase, the chromatin bridges induced nuclear envelope rupture in interphase, accumulated the cytoplasmic 3' nuclease TREX1, and developed RPA-coated single stranded (ss) DNA. CRISPR knockouts showed that TREX1 contributed to the generation of the ssDNA and the resolution of the chromatin bridges. Post-crisis clones showed chromothripsis and kataegis, presumably resulting from DNA repair and APOBEC editing of the fragmented chromatin bridge DNA. We propose that chromothripsis in human cancer may arise through TREX1-mediated fragmentation of dicentric chromosomes formed in telomere crisis. GRCh37/hg19 No NA CTDB0467 Research 26687355 Maciejowski J, Li Y, Bosco N, Campbell PJ, de Lange T Chromothripsis and Kataegis Induced by Telomere Crisis Cell 2015 Dec 8 Retinal pigment epithelial cell line RPE-1 Next Generation Sequencing Homo sapiens X-33 Illumina X-ten Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA Telomere crisis occurs during tumorigenesis when depletion of the telomere reserve leads to frequent telomere fusions. The resulting dicentric chromosomes have been proposed to drive genome instability. Here, we examine the fate of dicentric human chromosomes in telomere crisis. We observed that dicentric chromosomes invariably persisted through mitosis and developed into 50-200 um chromatin bridges connecting the daughter cells. Before their resolution at 3-20 hr after anaphase, the chromatin bridges induced nuclear envelope rupture in interphase, accumulated the cytoplasmic 3' nuclease TREX1, and developed RPA-coated single stranded (ss) DNA. CRISPR knockouts showed that TREX1 contributed to the generation of the ssDNA and the resolution of the chromatin bridges. Post-crisis clones showed chromothripsis and kataegis, presumably resulting from DNA repair and APOBEC editing of the fragmented chromatin bridge DNA. We propose that chromothripsis in human cancer may arise through TREX1-mediated fragmentation of dicentric chromosomes formed in telomere crisis. GRCh37/hg19 No NA CTDB0468 Research 26687355 Maciejowski J, Li Y, Bosco N, Campbell PJ, de Lange T Chromothripsis and Kataegis Induced by Telomere Crisis Cell 2015 Dec 15 Retinal pigment epithelial cell line RPE-1 Next Generation Sequencing Homo sapiens X-37 Illumina X-ten Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA Telomere crisis occurs during tumorigenesis when depletion of the telomere reserve leads to frequent telomere fusions. The resulting dicentric chromosomes have been proposed to drive genome instability. Here, we examine the fate of dicentric human chromosomes in telomere crisis. We observed that dicentric chromosomes invariably persisted through mitosis and developed into 50-200 um chromatin bridges connecting the daughter cells. Before their resolution at 3-20 hr after anaphase, the chromatin bridges induced nuclear envelope rupture in interphase, accumulated the cytoplasmic 3' nuclease TREX1, and developed RPA-coated single stranded (ss) DNA. CRISPR knockouts showed that TREX1 contributed to the generation of the ssDNA and the resolution of the chromatin bridges. Post-crisis clones showed chromothripsis and kataegis, presumably resulting from DNA repair and APOBEC editing of the fragmented chromatin bridge DNA. We propose that chromothripsis in human cancer may arise through TREX1-mediated fragmentation of dicentric chromosomes formed in telomere crisis. GRCh37/hg19 No NA CTDB0469 Research 26687355 Maciejowski J, Li Y, Bosco N, Campbell PJ, de Lange T Chromothripsis and Kataegis Induced by Telomere Crisis Cell 2015 Dec 7,12 Retinal pigment epithelial cell line RPE-1 Next Generation Sequencing Homo sapiens 24-141 Illumina X-ten Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA Telomere crisis occurs during tumorigenesis when depletion of the telomere reserve leads to frequent telomere fusions. The resulting dicentric chromosomes have been proposed to drive genome instability. Here, we examine the fate of dicentric human chromosomes in telomere crisis. We observed that dicentric chromosomes invariably persisted through mitosis and developed into 50-200 um chromatin bridges connecting the daughter cells. Before their resolution at 3-20 hr after anaphase, the chromatin bridges induced nuclear envelope rupture in interphase, accumulated the cytoplasmic 3' nuclease TREX1, and developed RPA-coated single stranded (ss) DNA. CRISPR knockouts showed that TREX1 contributed to the generation of the ssDNA and the resolution of the chromatin bridges. Post-crisis clones showed chromothripsis and kataegis, presumably resulting from DNA repair and APOBEC editing of the fragmented chromatin bridge DNA. We propose that chromothripsis in human cancer may arise through TREX1-mediated fragmentation of dicentric chromosomes formed in telomere crisis. GRCh37/hg19 No NA CTDB0470 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 6 Neuroblastomas Next Generation Sequencing Homo sapiens N407T Complete Genomics Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0471 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 2 Neuroblastomas Next Generation Sequencing Homo sapiens N783T Complete Genomics MYCN Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0472 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 5 Neuroblastomas Next Generation Sequencing Homo sapiens N492T Complete Genomics TERT Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0473 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 5 Neuroblastomas Next Generation Sequencing Homo sapiens N753T Complete Genomics TERT Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0474 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 2,5 Neuroblastomas Next Generation Sequencing Homo sapiens N732T Complete Genomics MYCN;TERT Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0475 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 2,5 Neuroblastomas Next Generation Sequencing Homo sapiens N538T Complete Genomics MYCN;TERT Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0476 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 5 Neuroblastomas Next Generation Sequencing Homo sapiens N752T Complete Genomics TERT Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0477 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 8 Neuroblastomas Next Generation Sequencing Homo sapiens N481T Complete Genomics MYC Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0478 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 1 Neuroblastomas Next Generation Sequencing Homo sapiens N790T Complete Genomics Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0479 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 2 Neuroblastomas Next Generation Sequencing Homo sapiens N089T Complete Genomics MYCN Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0480 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 2 Neuroblastomas Next Generation Sequencing Homo sapiens N106T Complete Genomics MYCN Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0481 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 2 Neuroblastomas Next Generation Sequencing Homo sapiens N608T Complete Genomics MYCN Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0482 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 2,19 Neuroblastomas Next Generation Sequencing Homo sapiens N637T Complete Genomics MYCN Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0483 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 2 Neuroblastomas Next Generation Sequencing Homo sapiens N834T Complete Genomics MYCN Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0484 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 1 Neuroblastomas Next Generation Sequencing Homo sapiens N814T Complete Genomics Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0485 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 7 Neuroblastomas Next Generation Sequencing Homo sapiens N576T Complete Genomics Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0486 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 5 Neuroblastomas Next Generation Sequencing Homo sapiens N804T Complete Genomics Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0487 Research 26523776 Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA,, Molenaar JJ, Versteeg R TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors Nat Genet 2015 Dec 4,12,17 Neuroblastomas Next Generation Sequencing Homo sapiens N770T Complete Genomics CDK4 Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. GRCh37/hg19 Yes NA CTDB0488 Research 26439695 Tang MH, Dahlgren M, Brueffer C, Tjitrowirjo T, Winter C, Chen Y, Olsson E, Wang K, Torngren T, Sjostrom M, Grabau D, Bendahl PO, Ryden L, Nimeus E, Saal LH, Borg A, Gruvberger-Saal SK Remarkable similarities of chromosomal rearrangements between primary human breast cancers and matched distant metastases as revealed by whole-genome sequencing Oncotarget 2015 Nov 17,19 Breast cancer Next Generation Sequencing Homo sapiens P6 Illumina HiSeq 2000 Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden To better understand and characterize chromosomal structural variation during breast cancer progression, we enumerated chromosomal rearrangements for 11 patients by performing low-coverage whole-genome sequencing of 11 primary breast tumors and their 13 matched distant metastases. The tumor genomes harbored a median of 85 (range 18-404) rearrangements per tumor, with a median of 82 (26-310) in primaries compared to 87 (18-404) in distant metastases. Concordance between paired tumors from the same patient was high with a median of 89% of rearrangements shared (range 61-100%), whereas little overlap was found when comparing all possible pairings of tumors from different patients (median 3%). The tumors exhibited diverse genomic patterns of rearrangements: some carried events distributed throughout the genome while others had events mostly within densely clustered chromothripsis-like foci at a few chromosomal locations. Irrespectively, the patterns were highly conserved between the primary tumor and metastases from the same patient. Rearrangements occurred more frequently in genic areas than expected by chance and among the genes affected there was significant enrichment for cancer-associated genes including disruption of TP53, RB1, PTEN, and ESR1, likely contributing to tumor development. Our findings are most consistent with chromosomal rearrangements being early events in breast cancer progression that remain stable during the development from primary tumor to distant metastasis. GRCh37/hg19 Yes NA CTDB0489 Research 26439695 Tang MH, Dahlgren M, Brueffer C, Tjitrowirjo T, Winter C, Chen Y, Olsson E, Wang K, Torngren T, Sjostrom M, Grabau D, Bendahl PO, Ryden L, Nimeus E, Saal LH, Borg A, Gruvberger-Saal SK Remarkable similarities of chromosomal rearrangements between primary human breast cancers and matched distant metastases as revealed by whole-genome sequencing Oncotarget 2015 Nov 16,17 Breast cancer Next Generation Sequencing Homo sapiens P16 Illumina HiSeq 2000 Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden To better understand and characterize chromosomal structural variation during breast cancer progression, we enumerated chromosomal rearrangements for 11 patients by performing low-coverage whole-genome sequencing of 11 primary breast tumors and their 13 matched distant metastases. The tumor genomes harbored a median of 85 (range 18-404) rearrangements per tumor, with a median of 82 (26-310) in primaries compared to 87 (18-404) in distant metastases. Concordance between paired tumors from the same patient was high with a median of 89% of rearrangements shared (range 61-100%), whereas little overlap was found when comparing all possible pairings of tumors from different patients (median 3%). The tumors exhibited diverse genomic patterns of rearrangements: some carried events distributed throughout the genome while others had events mostly within densely clustered chromothripsis-like foci at a few chromosomal locations. Irrespectively, the patterns were highly conserved between the primary tumor and metastases from the same patient. Rearrangements occurred more frequently in genic areas than expected by chance and among the genes affected there was significant enrichment for cancer-associated genes including disruption of TP53, RB1, PTEN, and ESR1, likely contributing to tumor development. Our findings are most consistent with chromosomal rearrangements being early events in breast cancer progression that remain stable during the development from primary tumor to distant metastasis. GRCh37/hg19 Yes NA CTDB0490 Research 26439695 Tang MH, Dahlgren M, Brueffer C, Tjitrowirjo T, Winter C, Chen Y, Olsson E, Wang K, Torngren T, Sjostrom M, Grabau D, Bendahl PO, Ryden L, Nimeus E, Saal LH, Borg A, Gruvberger-Saal SK Remarkable similarities of chromosomal rearrangements between primary human breast cancers and matched distant metastases as revealed by whole-genome sequencing Oncotarget 2015 Nov 11 Breast cancer Next Generation Sequencing Homo sapiens P17 Illumina HiSeq 2000 Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden To better understand and characterize chromosomal structural variation during breast cancer progression, we enumerated chromosomal rearrangements for 11 patients by performing low-coverage whole-genome sequencing of 11 primary breast tumors and their 13 matched distant metastases. The tumor genomes harbored a median of 85 (range 18-404) rearrangements per tumor, with a median of 82 (26-310) in primaries compared to 87 (18-404) in distant metastases. Concordance between paired tumors from the same patient was high with a median of 89% of rearrangements shared (range 61-100%), whereas little overlap was found when comparing all possible pairings of tumors from different patients (median 3%). The tumors exhibited diverse genomic patterns of rearrangements: some carried events distributed throughout the genome while others had events mostly within densely clustered chromothripsis-like foci at a few chromosomal locations. Irrespectively, the patterns were highly conserved between the primary tumor and metastases from the same patient. Rearrangements occurred more frequently in genic areas than expected by chance and among the genes affected there was significant enrichment for cancer-associated genes including disruption of TP53, RB1, PTEN, and ESR1, likely contributing to tumor development. Our findings are most consistent with chromosomal rearrangements being early events in breast cancer progression that remain stable during the development from primary tumor to distant metastasis. GRCh37/hg19 Yes NA CTDB0491 Research 26439695 Tang MH, Dahlgren M, Brueffer C, Tjitrowirjo T, Winter C, Chen Y, Olsson E, Wang K, Torngren T, Sjostrom M, Grabau D, Bendahl PO, Ryden L, Nimeus E, Saal LH, Borg A, Gruvberger-Saal SK Remarkable similarities of chromosomal rearrangements between primary human breast cancers and matched distant metastases as revealed by whole-genome sequencing Oncotarget 2015 Nov 3 Breast cancer Next Generation Sequencing Homo sapiens P20 Illumina HiSeq 2000 Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden To better understand and characterize chromosomal structural variation during breast cancer progression, we enumerated chromosomal rearrangements for 11 patients by performing low-coverage whole-genome sequencing of 11 primary breast tumors and their 13 matched distant metastases. The tumor genomes harbored a median of 85 (range 18-404) rearrangements per tumor, with a median of 82 (26-310) in primaries compared to 87 (18-404) in distant metastases. Concordance between paired tumors from the same patient was high with a median of 89% of rearrangements shared (range 61-100%), whereas little overlap was found when comparing all possible pairings of tumors from different patients (median 3%). The tumors exhibited diverse genomic patterns of rearrangements: some carried events distributed throughout the genome while others had events mostly within densely clustered chromothripsis-like foci at a few chromosomal locations. Irrespectively, the patterns were highly conserved between the primary tumor and metastases from the same patient. Rearrangements occurred more frequently in genic areas than expected by chance and among the genes affected there was significant enrichment for cancer-associated genes including disruption of TP53, RB1, PTEN, and ESR1, likely contributing to tumor development. Our findings are most consistent with chromosomal rearrangements being early events in breast cancer progression that remain stable during the development from primary tumor to distant metastasis. GRCh37/hg19 Yes NA CTDB0492 Research 26312826 Bertelsen B, Nazaryan-Petersen L, Sun W, Mehrjouy MM, Xie G, Chen W, Hjermind LE, Taschner PE, Tumer Z A germline chromothripsis event stably segregating in 11 individuals through three generations Genet Med 2016 May 3 Gilles de la Tourette syndrome Next Generation Sequencing Homo sapiens II-6 Illumina HiSeq2000 hs3:135821271-135827387,hs3:138506677-138509766;hs3:137890352-137896723,hs3:138510303-138516517;hs3:142214220-142218199,hs3:135827724-135833075;hs3:137728817-137735850,hs5:118834950-118841284;hs5:118826179-118833935,hs3:137876903-137889696;hs3:137845421-137852283,hs3:142218739-142223545 A4GNT;ATR;CLDN18;DBR1;DZIP1L;HSD17B4;PPP2R3A Department of Clinical Genetics, Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Glostrup, Denmark PURPOSE: Parentally transmitted germ-line chromothripsis (G-CTH) has been identified in only a few cases. Most of these rearrangements were stably transmitted, in an unbalanced form, from a healthy mother to her child with congenital abnormalities probably caused by de novo copy-number changes of dosage sensitive genes. We describe a G-CTH transmitted through three generations in 11 healthy carriers. METHODS: Conventional cytogenetic analysis, mate-pair sequencing, and polymerase chain reaction (PCR) were used to identify the chromosome rearrangement and characterize the breakpoints in all three generations. RESULTS: We identified an apparently balanced translocation t(3;5), later shown to be a G-CTH, in all individuals of a three-generation family. The G-CTH stably segregated without occurrence of additional rearrangements; however, several spontaneous abortions were reported, possibly due to unbalanced transmission. Although seven protein-coding genes are interrupted, no clinical features can be definitively attributed to the affected genes. However, it can be speculated that truncation of one of these genes, encoding ataxia-telangiectasia and Rad3-related protein kinase (ATR), a key component of the DNA damage response, may be related to G-CTH formation. CONCLUSION: G-CTH rearrangements are not always associated with abnormal phenotypes and may be misinterpreted as balanced two-way translocations, suggesting that G-CTH is an underdiagnosed phenomenon.Genet Med 18 5, 494-500. GRCh37/hg19 No CLDN18,HSD17B4;HSD17B4,DBR1 CTDB0493 Research 29073611 Kato T, Ouchi Y, Inagaki H, Makita Y, Mizuno S, Kajita M, Ikeda T, Takeuchi K, Kurahashi H Genomic Characterization of Chromosomal Insertions: Insights into the Mechanisms Underlying Chromothripsis Cytogenet Genome Res. 2017 Oct 4,14 Developmental delay Next Generation Sequencing Homo sapiens case_1 Illumina HiSeq 1500 chr14:0-104549510:0;chr14:104549511-107285437:-1;chr14:107285438-107349540:0;chr4:0-156376845:0;chr4:156376846-169441822:1;chr4:169441823-190659208:0;chr4:190659209-190957473:1;chr4:190957474-191154276:0 Division of Molecular Genetics, Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Toyoake, Japan Chromosomal insertions are rare structural rearrangements, and the molecular mechanisms underlying their origin are unknown. In this study, we used whole genome sequencing to analyze breakpoints and junction sequences in 4 patients with chromosomal insertions. Our analysis revealed that none of the 4 cases involved a simple insertion mediated by a 3-chromosomal breakage and rejoining events. The inserted fragments consisted of multiple pieces derived from a localized genomic region, which were shuffled and rejoined in a disorderly fashion with variable copy number alterations. The junctions were blunt ended or with short microhomologies or short microinsertions, suggesting the involvement of nonhomologous end-joining. In one case, analysis of the parental origin of the chromosomes using nucleotide variations within the insertion revealed that maternal chromosomal segments were inserted into the paternal chromosome. This patient also carried both maternal alleles, suggesting the presence of zygotic trisomy. These data indicate that chromosomal shattering may occur in association with trisomy rescue in the early postzygotic stage. GRCh37/hg19 no NA CTDB0494 Research 29073611 Kato T, Ouchi Y, Inagaki H, Makita Y, Mizuno S, Kajita M, Ikeda T, Takeuchi K, Kurahashi H Genomic Characterization of Chromosomal Insertions: Insights into the Mechanisms Underlying Chromothripsis Cytogenet Genome Res. 2017 Oct 8,10,12 Langer-Giedion syndrome Next Generation Sequencing Homo sapiens case_3 Illumina HiSeq 1500 chr8:0-114340064:0;chr8:114340065-114527620:-1;chr8:114527621-114806299:0;chr8:114806300-114925879:-1;chr8:114925880-115101168:0;chr8:115101169-122616401:-1;chr8:122616402-146364022:0 Division of Molecular Genetics, Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Toyoake, Japan Chromosomal insertions are rare structural rearrangements, and the molecular mechanisms underlying their origin are unknown. In this study, we used whole genome sequencing to analyze breakpoints and junction sequences in 4 patients with chromosomal insertions. Our analysis revealed that none of the 4 cases involved a simple insertion mediated by a 3-chromosomal breakage and rejoining events. The inserted fragments consisted of multiple pieces derived from a localized genomic region, which were shuffled and rejoined in a disorderly fashion with variable copy number alterations. The junctions were blunt ended or with short microhomologies or short microinsertions, suggesting the involvement of nonhomologous end-joining. In one case, analysis of the parental origin of the chromosomes using nucleotide variations within the insertion revealed that maternal chromosomal segments were inserted into the paternal chromosome. This patient also carried both maternal alleles, suggesting the presence of zygotic trisomy. These data indicate that chromosomal shattering may occur in association with trisomy rescue in the early postzygotic stage. GRCh37/hg19 no NA CTDB0495 Research 29073611 Kato T, Ouchi Y, Inagaki H, Makita Y, Mizuno S, Kajita M, Ikeda T, Takeuchi K, Kurahashi H Genomic Characterization of Chromosomal Insertions: Insights into the Mechanisms Underlying Chromothripsis Cytogenet Genome Res. 2017 Oct 7 Recurrent pregnancy loss Next Generation Sequencing Homo sapiens case_4 Illumina HiSeq 1500 chr7:25471046¨C38067611:-1 Division of Molecular Genetics, Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Toyoake, Japan Chromosomal insertions are rare structural rearrangements, and the molecular mechanisms underlying their origin are unknown. In this study, we used whole genome sequencing to analyze breakpoints and junction sequences in 4 patients with chromosomal insertions. Our analysis revealed that none of the 4 cases involved a simple insertion mediated by a 3-chromosomal breakage and rejoining events. The inserted fragments consisted of multiple pieces derived from a localized genomic region, which were shuffled and rejoined in a disorderly fashion with variable copy number alterations. The junctions were blunt ended or with short microhomologies or short microinsertions, suggesting the involvement of nonhomologous end-joining. In one case, analysis of the parental origin of the chromosomes using nucleotide variations within the insertion revealed that maternal chromosomal segments were inserted into the paternal chromosome. This patient also carried both maternal alleles, suggesting the presence of zygotic trisomy. These data indicate that chromosomal shattering may occur in association with trisomy rescue in the early postzygotic stage. GRCh37/hg19 no NA CTDB0493 Research 29073611 Kato T, Ouchi Y, Inagaki H, Makita Y, Mizuno S, Kajita M, Ikeda T, Takeuchi K, Kurahashi H Genomic Characterization of Chromosomal Insertions: Insights into the Mechanisms Underlying Chromothripsis Cytogenet Genome Res. 2017 Oct 4,14 Developmental delay Next Generation Sequencing Homo sapiens case_1 Illumina HiSeq 1500 chr14:0-104549510:0;chr14:104549511-107285437:-1;chr14:107285438-107349540:0;chr4:0-156376845:0;chr4:156376846-169441822:1;chr4:169441823-190659208:0;chr4:190659209-190957473:1;chr4:190957474-191154276:0 Division of Molecular Genetics, Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Toyoake, Japan Chromosomal insertions are rare structural rearrangements, and the molecular mechanisms underlying their origin are unknown. In this study, we used whole genome sequencing to analyze breakpoints and junction sequences in 4 patients with chromosomal insertions. Our analysis revealed that none of the 4 cases involved a simple insertion mediated by a 3-chromosomal breakage and rejoining events. The inserted fragments consisted of multiple pieces derived from a localized genomic region, which were shuffled and rejoined in a disorderly fashion with variable copy number alterations. The junctions were blunt ended or with short microhomologies or short microinsertions, suggesting the involvement of nonhomologous end-joining. In one case, analysis of the parental origin of the chromosomes using nucleotide variations within the insertion revealed that maternal chromosomal segments were inserted into the paternal chromosome. This patient also carried both maternal alleles, suggesting the presence of zygotic trisomy. These data indicate that chromosomal shattering may occur in association with trisomy rescue in the early postzygotic stage. GRCh37/hg19 no NA CTDB0494 Research 29073611 Kato T, Ouchi Y, Inagaki H, Makita Y, Mizuno S, Kajita M, Ikeda T, Takeuchi K, Kurahashi H Genomic Characterization of Chromosomal Insertions: Insights into the Mechanisms Underlying Chromothripsis Cytogenet Genome Res. 2017 Oct 8,10,12 Langer-Giedion syndrome Next Generation Sequencing Homo sapiens case_3 Illumina HiSeq 1500 chr8:0-114340064:0;chr8:114340065-114527620:-1;chr8:114527621-114806299:0;chr8:114806300-114925879:-1;chr8:114925880-115101168:0;chr8:115101169-122616401:-1;chr8:122616402-146364022:0 Division of Molecular Genetics, Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Toyoake, Japan Chromosomal insertions are rare structural rearrangements, and the molecular mechanisms underlying their origin are unknown. In this study, we used whole genome sequencing to analyze breakpoints and junction sequences in 4 patients with chromosomal insertions. Our analysis revealed that none of the 4 cases involved a simple insertion mediated by a 3-chromosomal breakage and rejoining events. The inserted fragments consisted of multiple pieces derived from a localized genomic region, which were shuffled and rejoined in a disorderly fashion with variable copy number alterations. The junctions were blunt ended or with short microhomologies or short microinsertions, suggesting the involvement of nonhomologous end-joining. In one case, analysis of the parental origin of the chromosomes using nucleotide variations within the insertion revealed that maternal chromosomal segments were inserted into the paternal chromosome. This patient also carried both maternal alleles, suggesting the presence of zygotic trisomy. These data indicate that chromosomal shattering may occur in association with trisomy rescue in the early postzygotic stage. GRCh37/hg19 no NA CTDB0495 Research 29073611 Kato T, Ouchi Y, Inagaki H, Makita Y, Mizuno S, Kajita M, Ikeda T, Takeuchi K, Kurahashi H Genomic Characterization of Chromosomal Insertions: Insights into the Mechanisms Underlying Chromothripsis Cytogenet Genome Res. 2017 Oct 7 Recurrent pregnancy loss Next Generation Sequencing Homo sapiens case_4 Illumina HiSeq 1500 chr7:25471046¨C38067611:-1 Division of Molecular Genetics, Institute for Comprehensive Medical Science (ICMS), Fujita Health University, Toyoake, Japan Chromosomal insertions are rare structural rearrangements, and the molecular mechanisms underlying their origin are unknown. In this study, we used whole genome sequencing to analyze breakpoints and junction sequences in 4 patients with chromosomal insertions. Our analysis revealed that none of the 4 cases involved a simple insertion mediated by a 3-chromosomal breakage and rejoining events. The inserted fragments consisted of multiple pieces derived from a localized genomic region, which were shuffled and rejoined in a disorderly fashion with variable copy number alterations. The junctions were blunt ended or with short microhomologies or short microinsertions, suggesting the involvement of nonhomologous end-joining. In one case, analysis of the parental origin of the chromosomes using nucleotide variations within the insertion revealed that maternal chromosomal segments were inserted into the paternal chromosome. This patient also carried both maternal alleles, suggesting the presence of zygotic trisomy. These data indicate that chromosomal shattering may occur in association with trisomy rescue in the early postzygotic stage. GRCh37/hg19 no NA CTDB0498 Research 28643781 Behjati S, Tarpey PS, Haase K, Ye H, Young MD, Alexandrov LB, Farndon SJ, Collord G, Wedge DC, Martincorena I, Cooke SL, Davies H, Mifsud W, Lidgren M, Martin S, Latimer C, Maddison M, Butler AP, Teague JW, Pillay N, Shlien A, McDermott U, Futreal PA, Baumhoer D, Zaikova O, Bjerkehagen B, Myklebost O, Amary MF, Tirabosco R, Van Loo P, Stratton MR, Flanagan AM, Campbell PJ Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma Nat Commun 2017 Jun 17 osteosarcoma Next Generation Sequencing Homo sapiens PD13494a Illumina HiSeq 2000 or 2500 chr17:0-525:0;chr17:10011784-12166176:-1;chr17:12166177-19613356:0;chr17:19613357-19631915:1;chr17:19631916-19637539:0;chr17:19637540-20115602:-1;chr17:20115603-37955801:0;chr17:2212616-6131809:0;chr17:37955802-39154663:-1;chr17:39154664-42027329:0;chr17:42027330-43183420:-1;chr17:43183421-46223221:0;chr17:46223222-47263785:-1;chr17:47263786-49209749:0;chr17:49209750-50524095:-1;chr17:50524096-52760719:0;chr17:526-2212615:-1;chr17:52760720-52869546:-1;chr17:52869547-55256018:0;chr17:55256019-59481373:-1;chr17:59481374-59483607:0;chr17:59483608-59496545:1;chr17:59496546-62072636:0;chr17:6131810-8099683:-1;chr17:62072637-62460996:-1;chr17:62460997-63642962:0;chr17:63642963-64366238:-1;chr17:64366239-66223666:0;chr17:66223667-66224617:1;chr17:66224618-68761858:0;chr17:68761859-70317514:-1;chr17:70317515-72407979:0;chr17:72407980-72852176:-1;chr17:72852177-75211311:0;chr17:75211312-76484046:-1;chr17:76484047-78925648:0;chr17:78925649-79447708:1;chr17:79447709-81195210:0;chr17:8099684-10011783:0 hs17:6002131-6002131,hs17:76512941-76512941;hs17:8195283-8195283,hs17:72278658-72278658;hs17:29435055-29435055,hs17:74696121-74696121;hs17:36621985-36621985,hs17:71799270-71799270;hs17:5031609-5031609,hs17:76995509-76995509;hs17:35727788-35727788,hs17:45352944-45352944;hs17:43371172-43371172,hs17:75207133-75207133;hs17:43489202-43489202,hs17:65411876-65411876;hs17:5998463-5998463,hs17:9262131-9262131;hs17:18219797-18219797,hs17:49243712-49243712;hs17:74465166-74465166,hs17:75204056-75204056;hs17:2397473-2397473,hs17:4445387-4445387;hs17:8938596-8938596,hs17:14020207-14020207;hs17:9050096-9050096,hs17:15953456-15953456;hs17:27066543-27066543,hs17:43149575-43149575;hs17:28070932-28070932,hs17:70760639-70760639;hs17:42947261-42947261,hs17:78036737-78036737;hs17:61370071-61370071,hs17:78039749-78039749;hs17:61325669-61325669,hs17:61459353-61459353;hs17:4983123-4983123,hs17:52980417-52980417;hs2:172724085-172724085,hs3:195029071-195029071;hs17:804709-804709,hs17:2163170-2163170;hs17:8988473-8988473,hs17:73253586-73253586;hs17:9052119-9052119,hs17:15428516-15428516;hs17:9874990-9874990,hs17:29510134-29510134;hs17:20083102-20083102,hs17:58318005-58318005;hs17:28731307-28731307,hs17:45348063-45348063;hs17:29447172-29447172,hs17:35722665-35722665;hs17:47858941-47858941,hs17:65008939-65008939;hs17:53367753-53367753,hs17:70752529-70752529;hs17:18167351-18167351,hs17:53145578-53145578;hs17:80586124-80586124,hs17:80586364-80586364;hs17:8343725-8343725,hs17:74460108-74460108;hs17:28739504-28739504,hs17:46661765-46661765;hs17:32174549-32174549,hs17:38395470-38395470;hs17:37963078-37963078,hs17:65228553-65228553;hs17:41975464-41975464,hs17:74711175-74711175;hs17:64404891-64404891,hs17:74734116-74734116;hs17:10458034-10458034,hs17:15219242-15219242;hs17:12481508-12481508,hs17:54236471-54236471;hs17:19342484-19342484,hs17:61318424-61318424;hs17:48054957-48054957,hs17:77977705-77977705;hs17:20557514-20557514,hs17:70441836-70441836;hs17:213366-213366,hs17:61382185-61382185;hs17:2651786-2651786,hs17:47250503-47250503;hs17:2654683-2654683,hs17:37973149-37973149;hs17:3412684-3412684,hs17:5867556-5867556;hs17:3419397-3419397,hs17:69428796-69428796;hs17:4449301-4449301,hs17:74806307-74806307;hs17:4545103-4545103,hs17:63334128-63334128;hs17:4940003-4940003,hs17:45990041-45990041;hs17:4949555-4949555,hs17:21946524-21946524;hs17:4952722-4952722,hs17:8995722-8995722;hs17:4980804-4980804,hs17:19640408-19640408;hs17:5028887-5028887,hs17:5859942-5859942;hs17:5760414-5760414,hs17:31795439-31795439;hs17:5764284-5764284,hs17:30935774-30935774;hs17:6132082-6132082,hs17:38049947-38049947;hs17:7336765-7336765,hs17:80594070-80594070;hs17:8099144-8099144,hs17:65404591-65404591;hs17:8201222-8201222,hs17:30329612-30329612;hs17:9232609-9232609,hs17:9640543-9640543;hs17:9269079-9269079,hs17:19790308-19790308;hs17:9645548-9645548,hs17:12728401-12728401;hs17:10136254-10136254,hs17:43378581-43378581;hs17:10470646-10470646,hs17:59626090-59626090;hs17:10511141-10511141,hs17:69575490-69575490;hs17:10657269-10657269,hs17:30323555-30323555;hs17:12987253-12987253,hs17:68736750-68736750;hs17:13104044-13104044,hs17:27068734-27068734;hs17:13366466-13366466,hs17:30922429-30922429;hs17:13403688-13403688,hs17:53891308-53891308;hs17:14016159-14016159,hs17:50499779-50499779;hs17:14519253-14519253,hs17:41307584-41307584;hs17:14687573-14687573,hs17:59629864-59629864;hs17:15189386-15189386,hs17:45982995-45982995;hs17:15961861-15961861,hs17:36811372-36811372;hs17:16995699-16995699,hs17:62683699-62683699;hs17:17002085-17002085,hs17:35149274-35149274;hs17:17098436-17098436,hs17:61684068-61684068;hs17:17192477-17192477,hs17:31791266-31791266;hs17:19846885-19846885,hs17:54810414-54810414;hs17:20471132-20471132,hs17:61462655-61462655;hs17:21952665-21952665,hs17:68744390-68744390;hs17:25777357-25777357,hs17:53344443-53344443;hs17:25785621-25785621,hs17:34833782-34833782;hs17:26206324-26206324,hs17:62102202-62102202;hs17:26245115-26245115,hs17:30103219-30103219;hs17:29199843-29199843,hs17:52760250-52760250;hs17:29504661-29504661,hs17:59564527-59564527;hs17:30110281-30110281,hs17:57347628-57347628;hs17:31196775-31196775,hs17:69793211-69793211;hs17:32178137-32178137,hs17:52653092-52653092;hs17:33701470-33701470,hs17:70436529-70436529;hs17:33711513-33711513,hs17:43388491-43388491;hs17:35046492-35046492,hs17:72008682-72008682;hs17:35049752-35049752,hs17:66745042-66745042;hs17:35151098-35151098,hs17:65020701-65020701;hs17:37772427-37772427,hs17:54815883-54815883;hs17:37775218-37775218,hs17:70371926-70371926;hs17:38377377-38377377,hs17:48922509-48922509;hs17:38380961-38380961,hs17:40603225-40603225;hs17:39129076-39129076,hs17:52867836-52867836;hs17:40601243-40601243,hs17:45892256-45892256;hs17:40827446-40827446,hs17:54228538-54228538;hs17:42806100-42806100,hs17:70364365-70364365;hs17:43486990-43486990,hs17:54146357-54146357;hs17:47356970-47356970,hs17:69156847-69156847;hs17:47842215-47842215,hs17:68742884-68742884;hs17:47854660-47854660,hs17:70294048-70294048;hs17:47937280-47937280,hs17:62669191-62669191;hs17:48335601-48335601,hs17:72892245-72892245;hs17:48338211-48338211,hs17:48929124-48929124;hs17:49598550-49598550,hs17:55481747-55481747;hs17:52640943-52640943,hs17:52971990-52971990;hs17:53136541-53136541,hs17:69674410-69674410;hs17:53877102-53877102,hs17:78291131-78291131;hs17:54141218-54141218,hs17:70720309-70720309;hs17:57082084-57082084,hs17:72383364-72383364;hs17:57970286-57970286,hs17:69666723-69666723;hs17:63629123-63629123,hs17:74621483-74621483;hs17:69128320-69128320,hs17:72432695-72432695;hs17:70305771-70305771,hs17:77969891-77969891;hs17:70305771-70305771,hs17:77969891-77969891;hs17:71794422-71794422,hs17:72013973-72013973;hs17:72379360-72379360,hs17:76991206-76991206;hs17:74258515-74258515,hs17:74808848-74808848 TP53;MAP2K4;NF1 Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike. GRCh37/hg19 Yes NA CTDB0499 Research 28512242 Kloosterman WP, Coebergh van den Braak RRJ, Pieterse M, van Roosmalen MJ, Sieuwerts AM, Stangl C, Brunekreef R, Lalmahomed ZS, Ooft S, van Galen A, Smid M, Lefebvre A, Zwartkruis F, Martens JWM, Foekens JA, Biermann K, Koudijs MJ, Ijzermans JNM, Voest EE A Systematic Analysis of Oncogenic Gene Fusions in Primary Colon Cancer Cancer Res 2017 Jul X Colorectal cancer Next Generation Sequencing Homo sapiens A1266 Illumina HiSeq2500 or NextSeq Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, CX Utrecht, the Netherlands Genomic rearrangements that give rise to oncogenic gene fusions can offer actionable targets for cancer therapy. Here we present a systematic analysis of oncogenic gene fusions among a clinically well-characterized, prospectively collected set of 278 primary colon cancers spanning diverse tumor stages and clinical outcomes. Gene fusions and somatic genetic variations were identified in fresh frozen clinical specimens by Illumina RNA-sequencing, the STAR fusion gene detection pipeline, and GATK RNA-seq variant calling. We considered gene fusions to be pathogenically relevant when recurrent, producing divergent gene expression (outlier analysis), or as functionally important (e.g., kinase fusions). Overall, 2.5% of all specimens were defined as harboring a relevant gene fusion (kinase fusions 1.8%). Novel configurations of BRAF, NTRK3, and RET gene fusions resulting from chromosomal translocations were identified. An R-spondin fusion was found in only one tumor (0.35%), much less than an earlier reported frequency of 10% in colorectal cancers. We also found a novel fusion involving USP9X-ERAS formed by chromothripsis and leading to high expression of ERAS, a constitutively active RAS protein normally expressed only in embryonic stem cells. This USP9X-ERAS fusion appeared highly oncogenic on the basis of its ability to activate AKT signaling. Oncogenic fusions were identified only in lymph node-negative tumors that lacked BRAF or KRAS mutations. In summary, we identified several novel oncogenic gene fusions in colorectal cancer that may drive malignant development and offer new targets for personalized therapy. GRCh37/hg19 Yes USP9X,ERAS CTDB0500 Research 28260531 Collins RL, Brand H, Redin CE, Hanscom C, Antolik C, Stone MR, Glessner JT, Mason T, Pregno G, Dorrani N, Mandrile G, Giachino D, Perrin D, Walsh C, Cipicchio M, Costello M, Stortchevoi A, An JY, Currall BB, Seabra CM, Ragavendran A, Margolin L, Martinez-Agosto JA, Lucente D, Levy B, Sanders SJ, Wapner RJ, Quintero-Rivera F, Kloosterman W, Talkowski ME Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome Genome Biol 2017 Mar 1,12,14,15 Autism spectrum disorder Next Generation Sequencing Homo sapiens TL010 Illumina HiSeq 2000 /2500 chr14:0-77704851:0;chr14:77704852-77739092:-1;chr14:77739093-107349540:0;chr6:0-99267814:0;chr6:102567331-102657383:-1;chr6:102657384-103737414:0;chr6:103737415-103763292:-1;chr6:103763293-116305817:0;chr6:116305818-116423965:-1;chr6:116423966-171115067:0;chr6:99267815-99840246:-1;chr6:99840247-102567330:0 LOC101927314;ASCC3;NT5DC1;LOC643770;NUMB;SLC41A2;ELMSAN1;DLST;RAD51B;ESRRB;COQ3;PNISR;AMD1;LAMA4;RGS6;TMEM63C;POMT2;SV2B;DNAL1;LAMA2;NCOA7;GPHN;FRK;ACOT2;POU3F2;FBXL4;FAXC;NGB Molecular Neurogenetics Unit and Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, and Department of Neurology, Massachusetts General Hospital, Boston, MA, 02114, USA BACKGROUND: Structural variation (SV) influences genome organization and contributes to human disease. However, the complete mutational spectrum of SV has not been routinely captured in disease association studies. RESULTS: We sequenced 689 participants with autism spectrum disorder (ASD) and other developmental abnormalities to construct a genome-wide map of large SV. Using long-insert jumping libraries at 105X mean physical coverage and linked-read whole-genome sequencing from 10X Genomics, we document seven major SV classes at ~5 kb SV resolution. Our results encompass 11,735 distinct large SV sites, 38.1% of which are novel and 16.8% of which are balanced or complex. We characterize 16 recurrent subclasses of complex SV (cxSV), revealing that: (1) cxSV are larger and rarer than canonical SV; (2) each genome harbors 14 large cxSV on average; (3) 84.4% of large cxSVs involve inversion; and (4) most large cxSV (93.8%) have not been delineated in previous studies. Rare SVs are more likely to disrupt coding and regulatory non-coding loci, particularly when truncating constrained and disease-associated genes. We also identify multiple cases of catastrophic chromosomal rearrangements known as chromoanagenesis, including somatic chromoanasynthesis, and extreme balanced germline chromothripsis events involving up to 65 breakpoints and 60.6 Mb across four chromosomes, further defining rare categories of extreme cxSV. CONCLUSIONS: These data provide a foundational map of large SV in the morbid human genome and demonstrate a previously underappreciated abundance and diversity of cxSV that should be considered in genomic studies of human disease. GRCh37/hg19 No CTDB0501 Research 28260531 Collins RL, Brand H, Redin CE, Hanscom C, Antolik C, Stone MR, Glessner JT, Mason T, Pregno G, Dorrani N, Mandrile G, Giachino D, Perrin D, Walsh C, Cipicchio M, Costello M, Stortchevoi A, An JY, Currall BB, Seabra CM, Ragavendran A, Margolin L, Martinez-Agosto JA, Lucente D, Levy B, Sanders SJ, Wapner RJ, Quintero-Rivera F, Kloosterman W, Talkowski ME Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome Genome Biol 2017 Mar 2,7,8,9 Autism spectrum disorder Next Generation Sequencing Homo sapiens UTR22 Illumina HiSeq 2000 /2500 chr2:0-167032587:0;chr2:167032588-167393745:-1;chr2:167393746-243199373:0 AC0101273;WIPF1;XIRP2;ZNF385B;ACO1;NSMAF;FRMPD1;KIAA1715;TOX;UBAP2;SCN9A;SCN7A;LOC101929680 Molecular Neurogenetics Unit and Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, and Department of Neurology, Massachusetts General Hospital, Boston, MA, 02114, USA BACKGROUND: Structural variation (SV) influences genome organization and contributes to human disease. However, the complete mutational spectrum of SV has not been routinely captured in disease association studies. RESULTS: We sequenced 689 participants with autism spectrum disorder (ASD) and other developmental abnormalities to construct a genome-wide map of large SV. Using long-insert jumping libraries at 105X mean physical coverage and linked-read whole-genome sequencing from 10X Genomics, we document seven major SV classes at ~5 kb SV resolution. Our results encompass 11,735 distinct large SV sites, 38.1% of which are novel and 16.8% of which are balanced or complex. We characterize 16 recurrent subclasses of complex SV (cxSV), revealing that: (1) cxSV are larger and rarer than canonical SV; (2) each genome harbors 14 large cxSV on average; (3) 84.4% of large cxSVs involve inversion; and (4) most large cxSV (93.8%) have not been delineated in previous studies. Rare SVs are more likely to disrupt coding and regulatory non-coding loci, particularly when truncating constrained and disease-associated genes. We also identify multiple cases of catastrophic chromosomal rearrangements known as chromoanagenesis, including somatic chromoanasynthesis, and extreme balanced germline chromothripsis events involving up to 65 breakpoints and 60.6 Mb across four chromosomes, further defining rare categories of extreme cxSV. CONCLUSIONS: These data provide a foundational map of large SV in the morbid human genome and demonstrate a previously underappreciated abundance and diversity of cxSV that should be considered in genomic studies of human disease. GRCh37/hg19 No CTDB0502 Research 28260531 Collins RL, Brand H, Redin CE, Hanscom C, Antolik C, Stone MR, Glessner JT, Mason T, Pregno G, Dorrani N, Mandrile G, Giachino D, Perrin D, Walsh C, Cipicchio M, Costello M, Stortchevoi A, An JY, Currall BB, Seabra CM, Ragavendran A, Margolin L, Martinez-Agosto JA, Lucente D, Levy B, Sanders SJ, Wapner RJ, Quintero-Rivera F, Kloosterman W, Talkowski ME Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome Genome Biol 2017 Mar 19 Autism spectrum disorder Next Generation Sequencing Homo sapiens TL009 Illumina HiSeq 2000 /2500 chr19:0-16868159:0;chr19:16868160-22316097:-1;chr19:22316098-22477874:0;chr19:22477875-23580214:-1;chr19:23580215-29843543:0;chr19:29843544-30967207:-1;chr19:30967208-32841723:0;chr19:32841724-33908877:-1;chr19:33908878-35162171:0;chr19:35162172-35774420:-1;chr19:35774421-38262470:0;chr19:38262471-44025989:-1;chr19:44025990-51937752:0;chr19:51937753-52788019:-1;chr19:52788020-53006099:0;chr19:53006100-56225088:-1;chr19:56225089-58145137:0;chr19:58145138-58410428:1;chr19:58410429-59128983:0 ABHD8;ANKLE1;ANO8;ARMC6;ARRDC2;ATP13A1;B3GNT3;BABAM1;BST2;C19orf60;CCDC124;CERS1;CILP2;COLGALT1;COMP;COPE;CPAMD8;CRLF1;CRTC1;DDA1;DDX49;ELL;F2RL3;FAM129C;FCHO1;FKBP8;GATAD2A;GDF1;GDF15;GMIP;GTPBP3;HAPLN4;HAUS8;HOMER3;IFI30;IL12RB1;INSL3;ISYNA1;JAK3;JUND;KCNN1;KIAA1683;KLHL26;KXD1;LINC00663;LINC00664;LOC641367;LOC729966;LPAR2;LRRC25;LSM4;MAP1S;MAST3;MAU2;MEF2B;MEF2BNB;MEF2BNB-MEF2B;MIR1270-1;MIR1270-2;MIR3188;MIR3189;MPV17L2;MRPL34;MVB12A;MYO9B;NCAN;NDUFA13;NR2C2AP;NR2F6;NXNL1;OCEL1;PBX4;PDE4C;PGLS;PGPEP1;PIK3R2;PLVAP;RAB3A;RFXANK;RPL18A;SIN3B;SLC25A42;SLC27A1;SLC5A5;SNORA68;SSBP4;SUGP1;SUGP2;TM6SF2;TMEM161A;TMEM221;TMEM59L;TSSK6;UBA52;UNC13A;UPF1;USE1;USHBP1;YJEFN3;ZNF100;ZNF101;ZNF14;ZNF208;ZNF253;ZNF257;ZNF429;ZNF43;ZNF430;ZNF431;ZNF486;ZNF493;ZNF506;ZNF626;ZNF682;ZNF708;ZNF714;ZNF737;ZNF738;ZNF826P;ZNF85;ZNF90;ZNF93;IPO5P1;LINC01233;LOC100996349;LOC101929124;LOC101929144;LOC101929164;LOC440518;ZNF492;ZNF724P;ZNF728;ZNF730;ZNF91;ZNF98;ZNF99;C19orf12;CCNE1;PLEKHF1;POP4;URI1;VSTM2B;AC007773.2;ANKRD27;C19orf40;CEBPA;CEBPA-AS1;CEBPG;CEP89;DPY19L3;GPATCH1;LRP3;NUDT19;PDCD5;RGS9BP;RHPN2;SLC7A10;SLC7A9;TDRD12;WDR88;FAM187B;FXYD1;FXYD3;FXYD5;FXYD7;GRAMD1A;HPN;HPN-AS1;LGI4;LINC00904;LOC102723513;LOC400685;LSR;MIR6887;SCN1B;USF2;ZNF181;ZNF30;ZNF302;ZNF599;ZNF792;AC004603.4;AC006129.4;AC016582.2;ACTN4;ADCK4;AKT2;ARHGEF1;ATP1A3;ATP5SL;AXL;B3GNT8;B9D2;BCKDHA;BLVRB;C19orf33;C19orf47;C19orf54;CAPN12;CATSPERG;CCDC97;CCER2;CD177;CD79A;CEACAM1;CEACAM21;CEACAM3;CEACAM4;CEACAM5;CEACAM6;CEACAM7;CEACAM8;CIC;CLC;CNFN;CNTD2;CXCL17;CYP2A13;CYP2A6;CYP2A7;CYP2B6;CYP2B7P;CYP2F1;CYP2G1P;CYP2S1;DEDD2;DLL3;DMRTC2;DPF1;DYRK1B;ECH1;EGLN2;EID2;EID2B;EIF3K;ERF;ERICH4;EXOSC5;FAM98C;FBL;FBXO17;FBXO27;FCGBP;GGN;GMFG;GRIK5;GSK3A;HIPK4;HNRNPL;HNRNPUL1;IFNL1;IFNL2;IFNL3;IFNL4;ITPKC;KCNK6;LEUTX;LGALS13;LGALS14;LGALS16;LGALS17A;LGALS4;LGALS7;LGALS7B;LIPE;LIPE-AS1;LOC100129935;LOC100505622;LOC284344;LOC644554;LRFN1;LTBP4;LYPD3;LYPD4;MAP3K10;MAP4K1;MED29;MEGF8;MIA;MIA-RAB4B;MIR4323;MIR4530;MIR641;MIR6719;MIR6796;MIR6797;MIR8077;MRPS12;NCCRP1;NFKBIB;NUMBL;PAF1;PAFAH1B3;PAK4;PAPL;PCAT19;PHLDB3;PLD3;PLEKHG2;POU2F2;PPP1R14A;PRG1;PRR19;PRX;PSG1;PSG10P;PSG11;PSG2;PSG3;PSG4;PSG5;PSG6;PSG7;PSG8;PSG9;PSMC4;PSMD8;RAB4B;RAB4B-EGLN2;RABAC1;RASGRP4;RINL;RPS16;RPS19;RYR1;SAMD4B;SARS2;SELV;SERTAD1;SERTAD3;SHKBP1;SIPA1L3;SIRT2;SNRPA;SPINT2;SPRED3;SPTBN4;SUPT5H;SYCN;TEX101;TGFB1;TIMM50;TMEM145;TMEM91;TTC9B;WDR87;YIF1B;ZFP36;ZNF526;ZNF546;ZNF574;ZNF780A;ZNF780B;CEACAM18;FLJ30403;FPR1;FPR2;FPR3;HAS1;HCCAT3;LOC101928571;MIR125A;MIR643;MIR6801;MIR99B;MIRLET7E;PPP2R1A;SIGLEC12;SIGLEC14;SIGLEC5;SIGLEC6;SIGLEC8;SPACA6P;SPACA6P-AS;ZNF175;ZNF350;ZNF432;ZNF577;ZNF613;ZNF614;ZNF615;ZNF616;ZNF649;ZNF836;ZNF841;BIRC8;BRSK1;CACNG6;CACNG7;CACNG8;CCDC106;CDC42EP5;CNOT3;COX6B2;DNAAF3;DPRX;EPN1;EPS8L1;ERVV-1;ERVV-2;FAM71E2;FAM90A27P;FCAR;FIZ1;GP6;HSPBP1;IL11;ISOC2;KIR2DL1;KIR2DL3;KIR2DL4;KIR2DS4;KIR3DL1;KIR3DL2;KIR3DL3;KIR3DX1;LAIR1;LAIR2;LENG1;LENG8;LENG9;LILRA1;LILRA2;LILRA3;LILRA4;LILRA5;LILRA6;LILRB1;LILRB2;LILRB3;LILRB4;LILRB5;LILRP2;LOC100287534;LOC101928804;LOC284379;MBOAT7;MIR1283-1;MIR1283-2;MIR1323;MIR371A;MIR371B;MIR372;MIR373;MIR4752;MIR498;MIR512-1;MIR512-2;MIR515-1;MIR515-2;MIR516A1;MIR516A2;MIR516B1;MIR516B2;MIR517A;MIR517B;MIR517C;MIR518A1;MIR518A2;MIR518B;MIR518C;MIR518D;MIR518E;MIR518F;MIR519A1;MIR519A2;MIR519B;MIR519C;MIR519D;MIR519E;MIR520A;MIR520B;MIR520C;MIR520D;MIR520E;MIR520F;MIR520G;MIR520H;MIR521-1;MIR521-2;MIR522;MIR523;MIR524;MIR525;MIR526A1;MIR526A2;MIR526B;MIR527;MIR6802;MIR6803;MIR6804;MIR6805;MIR8061;MIR935;MYADM;NAT14;NCR1;NDUFA3;NLRP12;NLRP2;NLRP7;OSCAR;PPP1R12C;PPP6R1;PRKCG;PRPF31;PTPRH;RDH13;RNU6-35P;RNU6-64P;RPL28;RPS9;SBK2;SBK3;SHISA7;SSC5D;SUV420H2;SYT5;TARM1;TFPT;TMC4;TMEM150B;TMEM190;TMEM238;TMEM86B;TNNI3;TNNT1;TPM3P9;TSEN34;TTYH1;U2AF2;UBE2S;VN1R2;VN1R4;VSTM1;ZNF137P;ZNF160;ZNF28;ZNF320;ZNF321P;ZNF331;ZNF347;ZNF415;ZNF468;ZNF524;ZNF525;ZNF579;ZNF580;ZNF581;ZNF600;ZNF611;ZNF628;ZNF665;ZNF677;ZNF701;ZNF702P;ZNF761;ZNF765;ZNF784;ZNF808;ZNF813;ZNF816;ZNF816-ZNF321P;ZNF818P;ZNF83;ZNF845;ZNF865;FKBP1AP1;ZNF154;ZNF211;ZNF551;ZNF552;ZNF586;ZNF587;ZNF587B;ZNF671;ZNF776;ZNF814;ZSCAN4 Molecular Neurogenetics Unit and Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, and Department of Neurology, Massachusetts General Hospital, Boston, MA, 02114, USA BACKGROUND: Structural variation (SV) influences genome organization and contributes to human disease. However, the complete mutational spectrum of SV has not been routinely captured in disease association studies. RESULTS: We sequenced 689 participants with autism spectrum disorder (ASD) and other developmental abnormalities to construct a genome-wide map of large SV. Using long-insert jumping libraries at 105X mean physical coverage and linked-read whole-genome sequencing from 10X Genomics, we document seven major SV classes at ~5 kb SV resolution. Our results encompass 11,735 distinct large SV sites, 38.1% of which are novel and 16.8% of which are balanced or complex. We characterize 16 recurrent subclasses of complex SV (cxSV), revealing that: (1) cxSV are larger and rarer than canonical SV; (2) each genome harbors 14 large cxSV on average; (3) 84.4% of large cxSVs involve inversion; and (4) most large cxSV (93.8%) have not been delineated in previous studies. Rare SVs are more likely to disrupt coding and regulatory non-coding loci, particularly when truncating constrained and disease-associated genes. We also identify multiple cases of catastrophic chromosomal rearrangements known as chromoanagenesis, including somatic chromoanasynthesis, and extreme balanced germline chromothripsis events involving up to 65 breakpoints and 60.6 Mb across four chromosomes, further defining rare categories of extreme cxSV. CONCLUSIONS: These data provide a foundational map of large SV in the morbid human genome and demonstrate a previously underappreciated abundance and diversity of cxSV that should be considered in genomic studies of human disease. GRCh37/hg19 No CTDB0505 Research 28196983 Ratnaparkhe M, Hlevnjak M, Kolb T, Jauch A, Maass KK, Devens F, Rode A, Hovestadt V, Korshunov A, Pastorczak A, Mlynarski W, Sungalee S, Korbel J, Hoell J, Fischer U, Milde T, Kramm C, Nathrath M, Chrzanowska K, Tausch E, Takagi M, Taga T, Constantini S, Loeffen J, Meijerink J, Zielen S, Gohring G, Schlegelberger B, Maass E, Siebert R, Kunz J, Kulozik AE, Worst B, Jones DT, Pfister SM, Zapatka M, Lichter P, Ernst A Genomic profiling of Acute lymphoblastic leukemia in ataxia telangiectasia patients reveals tight link between ATM mutations and chromothripsis Leukemia 2017 Oct 14 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens patient_10 Illumina HiSeq X Ten Division of Molecular Genetics, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair. Using whole-genome sequencing, fluorescence in situ hybridization and RNA sequencing, we characterized the genomic landscape of Acute Lymphoblastic Leukemia (ALL) arising in patients with Ataxia Telangiectasia. We detected a high frequency of chromothriptic events in these tumors, specifically on acrocentric chromosomes, as compared with tumors from individuals with other types of DNA repair syndromes (27 cases total, 10 with Ataxia Telangiectasia). Our data suggest that the genomic landscape of Ataxia Telangiectasia ALL is clearly distinct from that of sporadic ALL. Mechanistically, short telomeres and compromised DNA damage response in cells of Ataxia Telangiectasia patients may be linked with frequent chromothripsis. Furthermore, we show that ATM loss is associated with increased chromothripsis prevalence in additional tumor entities. GRCh37/hg19 Yes CTDB0506 Research 28196983 Ratnaparkhe M, Hlevnjak M, Kolb T, Jauch A, Maass KK, Devens F, Rode A, Hovestadt V, Korshunov A, Pastorczak A, Mlynarski W, Sungalee S, Korbel J, Hoell J, Fischer U, Milde T, Kramm C, Nathrath M, Chrzanowska K, Tausch E, Takagi M, Taga T, Constantini S, Loeffen J, Meijerink J, Zielen S, Gohring G, Schlegelberger B, Maass E, Siebert R, Kunz J, Kulozik AE, Worst B, Jones DT, Pfister SM, Zapatka M, Lichter P, Ernst A Genomic profiling of Acute lymphoblastic leukemia in ataxia telangiectasia patients reveals tight link between ATM mutations and chromothripsis Leukemia 2017 Oct 22 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens patient_11 Illumina HiSeq X Ten Division of Molecular Genetics, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair. Using whole-genome sequencing, fluorescence in situ hybridization and RNA sequencing, we characterized the genomic landscape of Acute Lymphoblastic Leukemia (ALL) arising in patients with Ataxia Telangiectasia. We detected a high frequency of chromothriptic events in these tumors, specifically on acrocentric chromosomes, as compared with tumors from individuals with other types of DNA repair syndromes (27 cases total, 10 with Ataxia Telangiectasia). Our data suggest that the genomic landscape of Ataxia Telangiectasia ALL is clearly distinct from that of sporadic ALL. Mechanistically, short telomeres and compromised DNA damage response in cells of Ataxia Telangiectasia patients may be linked with frequent chromothripsis. Furthermore, we show that ATM loss is associated with increased chromothripsis prevalence in additional tumor entities. GRCh37/hg19 Yes CTDB0507 Research 28196983 Ratnaparkhe M, Hlevnjak M, Kolb T, Jauch A, Maass KK, Devens F, Rode A, Hovestadt V, Korshunov A, Pastorczak A, Mlynarski W, Sungalee S, Korbel J, Hoell J, Fischer U, Milde T, Kramm C, Nathrath M, Chrzanowska K, Tausch E, Takagi M, Taga T, Constantini S, Loeffen J, Meijerink J, Zielen S, Gohring G, Schlegelberger B, Maass E, Siebert R, Kunz J, Kulozik AE, Worst B, Jones DT, Pfister SM, Zapatka M, Lichter P, Ernst A Genomic profiling of Acute lymphoblastic leukemia in ataxia telangiectasia patients reveals tight link between ATM mutations and chromothripsis Leukemia 2017 Oct 14 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens patient_13 Illumina HiSeq X Ten Division of Molecular Genetics, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair. Using whole-genome sequencing, fluorescence in situ hybridization and RNA sequencing, we characterized the genomic landscape of Acute Lymphoblastic Leukemia (ALL) arising in patients with Ataxia Telangiectasia. We detected a high frequency of chromothriptic events in these tumors, specifically on acrocentric chromosomes, as compared with tumors from individuals with other types of DNA repair syndromes (27 cases total, 10 with Ataxia Telangiectasia). Our data suggest that the genomic landscape of Ataxia Telangiectasia ALL is clearly distinct from that of sporadic ALL. Mechanistically, short telomeres and compromised DNA damage response in cells of Ataxia Telangiectasia patients may be linked with frequent chromothripsis. Furthermore, we show that ATM loss is associated with increased chromothripsis prevalence in additional tumor entities. GRCh37/hg19 Yes CTDB0508 Research 28196983 Ratnaparkhe M, Hlevnjak M, Kolb T, Jauch A, Maass KK, Devens F, Rode A, Hovestadt V, Korshunov A, Pastorczak A, Mlynarski W, Sungalee S, Korbel J, Hoell J, Fischer U, Milde T, Kramm C, Nathrath M, Chrzanowska K, Tausch E, Takagi M, Taga T, Constantini S, Loeffen J, Meijerink J, Zielen S, Gohring G, Schlegelberger B, Maass E, Siebert R, Kunz J, Kulozik AE, Worst B, Jones DT, Pfister SM, Zapatka M, Lichter P, Ernst A Genomic profiling of Acute lymphoblastic leukemia in ataxia telangiectasia patients reveals tight link between ATM mutations and chromothripsis Leukemia 2017 Oct 21 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens patient_16 Illumina HiSeq X Ten Division of Molecular Genetics, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair. Using whole-genome sequencing, fluorescence in situ hybridization and RNA sequencing, we characterized the genomic landscape of Acute Lymphoblastic Leukemia (ALL) arising in patients with Ataxia Telangiectasia. We detected a high frequency of chromothriptic events in these tumors, specifically on acrocentric chromosomes, as compared with tumors from individuals with other types of DNA repair syndromes (27 cases total, 10 with Ataxia Telangiectasia). Our data suggest that the genomic landscape of Ataxia Telangiectasia ALL is clearly distinct from that of sporadic ALL. Mechanistically, short telomeres and compromised DNA damage response in cells of Ataxia Telangiectasia patients may be linked with frequent chromothripsis. Furthermore, we show that ATM loss is associated with increased chromothripsis prevalence in additional tumor entities. GRCh37/hg19 Yes CTDB0509 Research 28196983 Ratnaparkhe M, Hlevnjak M, Kolb T, Jauch A, Maass KK, Devens F, Rode A, Hovestadt V, Korshunov A, Pastorczak A, Mlynarski W, Sungalee S, Korbel J, Hoell J, Fischer U, Milde T, Kramm C, Nathrath M, Chrzanowska K, Tausch E, Takagi M, Taga T, Constantini S, Loeffen J, Meijerink J, Zielen S, Gohring G, Schlegelberger B, Maass E, Siebert R, Kunz J, Kulozik AE, Worst B, Jones DT, Pfister SM, Zapatka M, Lichter P, Ernst A Genomic profiling of Acute lymphoblastic leukemia in ataxia telangiectasia patients reveals tight link between ATM mutations and chromothripsis Leukemia 2017 Oct 14 Acute lymphoblastic leukemia Next Generation Sequencing Homo sapiens patient_25 Illumina HiSeq X Ten Division of Molecular Genetics, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair. Using whole-genome sequencing, fluorescence in situ hybridization and RNA sequencing, we characterized the genomic landscape of Acute Lymphoblastic Leukemia (ALL) arising in patients with Ataxia Telangiectasia. We detected a high frequency of chromothriptic events in these tumors, specifically on acrocentric chromosomes, as compared with tumors from individuals with other types of DNA repair syndromes (27 cases total, 10 with Ataxia Telangiectasia). Our data suggest that the genomic landscape of Ataxia Telangiectasia ALL is clearly distinct from that of sporadic ALL. Mechanistically, short telomeres and compromised DNA damage response in cells of Ataxia Telangiectasia patients may be linked with frequent chromothripsis. Furthermore, we show that ATM loss is associated with increased chromothripsis prevalence in additional tumor entities. GRCh37/hg19 Yes CTDB0510 Research 28126037 Middelkamp S, van Heesch S, Braat AK, de Ligt J, van Iterson M, Simonis M, van Roosmalen MJ, Kelder MJ, Kruisselbrink E, Hochstenbach R, Verbeek NE, Ippel EF, Adolfs Y, Pasterkamp RJ, Kloosterman WP, Kuijk EW, Cuppen E Molecular dissection of germline chromothripsis in a developmental context using patient-derived iPS cells Genome Med 2017 Jan 1,3,7,12 Multiple congenital abnormalities and/or mental retardation Next Generation Sequencing Homo sapiens 28085746_patient Illumina HiSeq 2500 AGR3;AGR2;TSPAN13;BZW2;ANKMY2;LRRC72;SOSTDC1;ISPD;MEOX2;agmo_7e;AGMO;PPM1H;C12orf61;MON2;USP15;FAM19A2;ETV1;DPYD;FOXP1;CNTN3;PDZRN3;EBLN2;PPP4R2;GXYLT2;SHQ1;RYBP;PROK2;GPR27;EIF4E3;foxp1_3b;hdac9_7g;HDAC9;FERD3L;TWIST1;dpyd_1b;PTBP2;RWDD3;TMEM56-RWDD3;TMEM56;ALG14;CNN3;SLC44A3;ROBO2;SRGAP1;TMEM5;DPY19L2;AVPR1A;ZNF717;THSD7A;TMEM106B;VWDE;SCIN;ARL4A;etv1_7d;DGKB;agmo_7d;AHR;SNX13;PRPS1L1;hdac9_7f Center for Molecular Medicine and Cancer Genomics Netherlands, Division Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, 3584CG, The Netherlands BACKGROUND: Germline chromothripsis causes complex genomic rearrangements that are likely to affect multiple genes and their regulatory contexts. The contribution of individual rearrangements and affected genes to the phenotypes of patients with complex germline genomic rearrangements is generally unknown. METHODS: To dissect the impact of germline chromothripsis in a relevant developmental context, we performed trio-based RNA expression analysis on blood cells, induced pluripotent stem cells (iPSCs), and iPSC-derived neuronal cells from a patient with de novo germline chromothripsis and both healthy parents. In addition, Hi-C and 4C-seq experiments were performed to determine the effects of the genomic rearrangements on transcription regulation of genes in the proximity of the breakpoint junctions. RESULTS: Sixty-seven genes are located within 1 Mb of the complex chromothripsis rearrangements involving 17 breakpoints on four chromosomes. We find that three of these genes (FOXP1, DPYD, and TWIST1) are both associated with developmental disorders and differentially expressed in the patient. Interestingly, the effect on TWIST1 expression was exclusively detectable in the patient's iPSC-derived neuronal cells, stressing the need for studying developmental disorders in the biologically relevant context. Chromosome conformation capture analyses show that TWIST1 lost genomic interactions with several enhancers due to the chromothripsis event, which likely led to deregulation of TWIST1 expression and contributed to the patient's craniosynostosis phenotype. CONCLUSIONS: We demonstrate that a combination of patient-derived iPSC differentiation and trio-based molecular profiling is a powerful approach to improve the interpretation of pathogenic complex genomic rearrangements. Here we have applied this approach to identify misexpression of TWIST1, FOXP1, and DPYD as key contributors to the complex congenital phenotype resulting from germline chromothripsis rearrangements. GRCh37/hg19 No CTDB0517 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 9 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0003 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0518 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 9,17,18,22 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0005 Illumina HiSeq 2500 CDKN2A; TP53;SMAD4 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0519 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 6,10 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0006 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0520 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 4 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0007 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0521 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 3,14,18,20 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0008 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0522 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 14 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0009 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0523 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 6,22 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0010 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0524 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 9,13 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0016 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0525 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 12,17,18 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0017 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0526 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 19 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0022 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0527 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 17 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0025 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0528 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 17,18 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0026 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0529 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 6,8,12,18 Pancreatic cancer Next Generation Sequencing Homo sapiens Ashpc_0027 Illumina HiSeq 2500 SMAD4;GATA6 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0530 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 4,7,8,10,12,18,21 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0015 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0531 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 12,18 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0044 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0532 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 18 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0072 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0533 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 9 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0077 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0534 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 1,14,15,18,20 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0080 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0535 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 4,5,6,8,10,14,15,20,22 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0081 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0536 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 8,13,15,16,18 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0082 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0537 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 12 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0085 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0538 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 7,11,14,15,16,22 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0101 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0539 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 1 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0104 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0540 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 3 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0105 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0541 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 7,12 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0109 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0542 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 1,3,6,8,17 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0111 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0543 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 10,12,18 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0132 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0544 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 8,14,18,19 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0145 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0545 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 16 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0162 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0546 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 19 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0170 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0547 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 9,18 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0171 Illumina HiSeq 2500 CDKN2A;SMAD4 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0548 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 11 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0174 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0549 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 3,11,13 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0175 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0550 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 3,8,17,18 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0210 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0551 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 6,10,12 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0217 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0552 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 12 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0226 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0553 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 6 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0228 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0554 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 6,7,8,12,15,18,21 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0230 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0555 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 1,4,8 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0236 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0556 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 2,5,6,21,X Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0237 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0557 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 13 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0239 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0558 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 18,21 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0240 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0559 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 4,18 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0261 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0560 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 1,3,11 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0268 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0561 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 4,14,16,18 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0274 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0562 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 19,22 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0279 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0563 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 6,9,11 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0287 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0564 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 3,4,9,12,18,20 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0290 Illumina HiSeq 2500 KRAS Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0565 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 1,6,9,11,12,15,17 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0297 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0566 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 7,12 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0300 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0567 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 14,18 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0303 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0568 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 2,5,11 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0305 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0569 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 6 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0307 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0570 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 1,5 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0324 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0571 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 3,7,8,11,12,18 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0325 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0572 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 13 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0326 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0573 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 1 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0328 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0574 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 9 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0341 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0575 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 1 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0345 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0576 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 1,15 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0347 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0577 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 2,6,11,12,17,18,20,21 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0356 Illumina HiSeq 2500 KRAS Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0578 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 11,16 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0387 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0579 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 14 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0407 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0580 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 6,8 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0410 Illumina HiSeq 2500 c-MYC Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0581 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 3 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0467 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0582 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 9 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0468 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0583 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 14,21 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0469 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0584 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 6 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0473 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0585 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 4,8,11 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0504 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0586 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 1,7,21 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0549 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0587 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 1,2,14,19 Pancreatic cancer Next Generation Sequencing Homo sapiens Pcsi_0572 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes CTDB0588 Research 27732578 Notta F, Chan-Seng-Yue M, Lemire M, Li Y, Wilson GW, Connor AA, Denroche RE, Liang SB, Brown AM, Kim JC, Wang T, Simpson JT, Beck T, Borgida A, Buchner N, Chadwick D, Hafezi-Bakhtiari S, Dick JE, Heisler L, Hollingsworth MA, Ibrahimov E, Jang GH, Johns J, Jorgensen LG, Law C, Ludkovski O, Lungu I, Ng K, Pasternack D, Petersen GM, Shlush LI, Timms L, Tsao MS, Wilson JM, Yung CK, Zogopoulos G, Bartlett JM, Alexandrov LB, Real FX, Cleary SP, Roehrl MH, McPherson JD, Stein LD, Hudson TJ, Campbell PJ, Gallinger S A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns Nature 2016 Oct 2,4 Pancreatic cancer Next Generation Sequencing Homo sapiens RAMP_0003 Illumina HiSeq 2500 Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Ancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours. GRCh37/hg19 Yes