Distinct Classes of Complex Structural Variation Uncovered across Thousands of Cancer Genome Graphs.
aneuploidy
cancer evolution
cancer genomics
chromothripsis
fragile sites
genome graphs
mutational processes
phasing
structural variation
superenhancers
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
09
11
2019
revised:
08
04
2020
accepted:
03
08
2020
entrez:
2
10
2020
pubmed:
3
10
2020
medline:
18
5
2021
Statut:
ppublish
Résumé
Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g., deletion) or complex (e.g., chromothripsis) structural variant classes. Applying a novel genome graph computational paradigm to analyze the topology of junction copy number (JCN) across 2,778 tumor whole-genome sequences, we uncovered three novel complex rearrangement phenomena: pyrgo, rigma, and tyfonas. Pyrgo are "towers" of low-JCN duplications associated with early-replicating regions, superenhancers, and breast or ovarian cancers. Rigma comprise "chasms" of low-JCN deletions enriched in late-replicating fragile sites and gastrointestinal carcinomas. Tyfonas are "typhoons" of high-JCN junctions and fold-back inversions associated with expressed protein-coding fusions, breakend hypermutation, and acral, but not cutaneous, melanomas. Clustering of tumors according to genome graph-derived features identified subgroups associated with DNA repair defects and poor prognosis.
Identifiants
pubmed: 33007263
pii: S0092-8674(20)30997-1
doi: 10.1016/j.cell.2020.08.006
pmc: PMC7912537
mid: NIHMS1665467
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
197-210.e32Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR000043
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA091955
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097404
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA247749
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210989
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA193313
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA194547
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA232465
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM132083
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests J.S.R.-F. reports receiving personal/consultancy fees from VolitionRx, Paige.AI, Goldman Sachs, REPARE Therapeutics, GRAIL, Ventana Medical Systems, Roche, Genentech, and InviCRO outside of the scope of the submitted work.
Références
Nat Methods. 2017 Sep;14(9):915-920
pubmed: 28714986
Cell. 2014 Nov 20;159(5):1015-1026
pubmed: 25416942
Nature. 2016 Oct 13;538(7624):201-206
pubmed: 27654912
Genome Res. 2012 Jun;22(6):993-1005
pubmed: 22456607
Cell Syst. 2016 Jul;3(1):99-101
pubmed: 27467250
Cell. 2013 Apr 25;153(3):666-77
pubmed: 23622249
BMC Bioinformatics. 2012 Apr 19;13 Suppl 6:S10
pubmed: 22537039
Biostatistics. 2004 Oct;5(4):557-72
pubmed: 15475419
Nat Genet. 2013 Oct;45(10):1134-40
pubmed: 24071852
Cell. 2013 Mar 14;152(6):1226-36
pubmed: 23498933
Nat Commun. 2017 Oct 31;8(1):1221
pubmed: 29089486
Mol Cell. 2011 Dec 23;44(6):966-77
pubmed: 22195969
Nature. 2019 May;569(7757):503-508
pubmed: 31068700
Nat Methods. 2015 Jun;12(6):527-30
pubmed: 25938371
Int J Mol Sci. 2012;13(9):11974-99
pubmed: 23109895
Bioinformatics. 2012 Sep 15;28(18):i333-i339
pubmed: 22962449
Genome Res. 2012 Feb;22(2):346-61
pubmed: 21994251
Ann Oncol. 2015 Jan;26(1):64-70
pubmed: 25319062
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
BMC Genomics. 2019 Apr 18;19(Suppl 9):985
pubmed: 30999860
Nat Genet. 2013 Sep;45(9):970-6
pubmed: 23852170
Nature. 2020 Feb;578(7793):112-121
pubmed: 32025012
Genome Res. 2015 Feb;25(2):189-200
pubmed: 25373142
Nature. 2012 Mar 28;483(7391):603-7
pubmed: 22460905
Nat Methods. 2009 Jan;6(1):99-103
pubmed: 19043412
Nat Struct Mol Biol. 2019 Jan;26(1):58-66
pubmed: 30598553
Nat Rev Cancer. 2018 Nov;18(11):696-705
pubmed: 30293088
Oncotarget. 2015 Oct 6;6(30):29087-96
pubmed: 26337081
Cell. 2014 Dec 18;159(7):1665-80
pubmed: 25497547
Nat Rev Cancer. 2015 Mar;15(3):166-80
pubmed: 25709118
Cell. 1996 Feb 23;84(4):587-97
pubmed: 8598045
Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):E1128-36
pubmed: 22065754
Genome Res. 2014 Nov;24(11):1881-93
pubmed: 25060187
Cell. 2017 Jul 27;170(3):507-521.e18
pubmed: 28735753
Mol Cell. 2012 May 25;46(4):424-35
pubmed: 22607975
Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15524-15533
pubmed: 31308241
Nat Methods. 2017 Jan;14(1):65-67
pubmed: 27892959
Nature. 2016 May 02;534(7605):47-54
pubmed: 27135926
Nature. 2018 Aug;560(7716):112-116
pubmed: 30022158
Science. 2012 May 4;336(6081):593-7
pubmed: 22556254
Cell. 2013 Nov 7;155(4):934-47
pubmed: 24119843
Genome Res. 2017 Jan;27(1):107-117
pubmed: 27986820
Nature. 2020 Feb;578(7793):82-93
pubmed: 32025007
Cancer. 2016 Nov 15;122(21):3354-3362
pubmed: 27533633
Cancer Lett. 2006 Jan 28;232(1):13-26
pubmed: 16236432
Bioinformatics. 2012 Feb 15;28(4):593-4
pubmed: 22199392
Nature. 2010 Feb 18;463(7283):899-905
pubmed: 20164920
Cell. 2011 Jan 7;144(1):27-40
pubmed: 21215367
Nature. 2020 Feb;578(7793):94-101
pubmed: 32025018
Oncoscience. 2015 Jul 31;2(7):618-28
pubmed: 26328271
Nature. 2019 Nov;575(7781):210-216
pubmed: 31645765
Genome Res. 2017 Dec;27(12):2050-2060
pubmed: 29097403
Nature. 2010 Feb 18;463(7283):893-8
pubmed: 20164919
Curr Opin Syst Biol. 2017 Feb;1:54-61
pubmed: 29177203
Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15770-5
pubmed: 17043225
Genome Biol. 2017 Jul 27;18(1):140
pubmed: 28750660
Cell Syst. 2016 Jul;3(1):21-34
pubmed: 27453446
Cell. 2019 Jun 13;177(7):1842-1857.e21
pubmed: 31155235
Nat Methods. 2018 Aug;15(8):591-594
pubmed: 30013048
Nat Rev Genet. 2018 Jun;19(6):329-346
pubmed: 29599501
Cancer Lett. 2006 Jan 28;232(1):27-36
pubmed: 16225988
Genome Res. 2010 Nov;20(11):1613-22
pubmed: 20805290
Cell. 2017 Jan 26;168(3):460-472.e14
pubmed: 28089356
Genome Res. 2018 Apr;28(4):581-591
pubmed: 29535149
Nat Genet. 2019 Mar;51(3):506-516
pubmed: 30718927
Genome Biol. 2016 Feb 22;17:31
pubmed: 26899170
Genome Res. 2012 Oct;22(10):1995-2007
pubmed: 22637570
Nature. 2017 May 11;545(7653):175-180
pubmed: 28467829
Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5546-51
pubmed: 23503850
Cell. 2017 Mar 23;169(1):13-23
pubmed: 28340338