StudyType	PubMedID	Author	Title	Journal	PublishDate	Chromosome	Disease	Technology	Species	CaseID	Platform	CNA	Connection	Gene	Affiliation	Abstract	GenomeAssembly	GEO	dbGaP	ENA	IsCancer	FusionGene
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
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
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
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
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
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