StudyType	PubMedID	Author	Title	Journal	PublishDate	Chromosome	Disease	Technology	Species	CaseID	Platform	CNA	Connection	Gene	Affiliation	Abstract	GenomeAssembly	GEO	dbGaP	ENA	IsCancer	FusionGene
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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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
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 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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
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 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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
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
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
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;hs7:375899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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
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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110794		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
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
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 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8-30563885,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
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
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 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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