Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development

被引：1741

作者：

Stephens, Philip J. ^{[1
]}

Greenman, Chris D. ^{[1
]}

Fu, Beiyuan ^{[1
]}

Yang, Fengtang ^{[1
]}

Bignell, Graham R. ^{[1
]}

Mudie, Laura J. ^{[1
]}

Pleasance, Erin D. ^{[1
]}

Lau, King Wai ^{[1
]}

Beare, David ^{[1
]}

Stebbings, Lucy A. ^{[1
]}

McLaren, Stuart ^{[1
]}

Lin, Meng-Lay ^{[1
]}

McBride, David J. ^{[1
]}

Varela, Ignacio ^{[1
]}

Nik-Zainal, Serena ^{[1
]}

Leroy, Catherine ^{[1
]}

Jia, Mingming ^{[1
]}

Menzies, Andrew ^{[1
]}

Butler, Adam P. ^{[1
]}

Teague, Jon W. ^{[1
]}

Quail, Michael A. ^{[1
]}

Burton, John ^{[1
]}

Swerdlow, Harold ^{[1
]}

Carter, Nigel P. ^{[1
]}

Morsberger, Laura A. ^{[2
,3
]}

Iacobuzio-Donahue, Christine ^{[2
,3
]}

Follows, George A. ^{[4
]}

Green, Anthony R. ^{[4
,5
]}

Flanagan, Adrienne M. ^{[6
,7
]}

Stratton, Michael R. ^{[1
,8
]}

Futreal, P. Andrew ^{[1
]}

Campbell, Peter J. ^{[1
,5
]}

机构：

[1] Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge CB10 1SA, England

[2] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA

[3] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21287 USA

[4] Addenbrookes Hosp, Dept Haematol, Cambridge CB2 0QQ, England

[5] Univ Cambridge, Dept Haematol, Cambridge CB2 0XY, England

[6] UCL, Inst Canc, London WC1E 6BT, England

[7] Royal Natl Orthopaed Hosp, Stanmore HA7 4LP, Middx, England

[8] Inst Canc Res, Sutton SM2 5NG, Surrey, England

来源：

CELL | 2011年 / 144卷 / 01期

基金：

英国惠康基金;

关键词：

CELL LUNG-CANCER; PANCREATIC-CANCER; TUMOR-SUPPRESSOR; MUTATIONS; EVOLUTION; INSTABILITY; SIGNATURES; RESOLUTION; SEQUENCE;

D O I：

10.1016/j.cell.2010.11.055

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in similar to 25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer.

引用

页码：27 / 40

页数：14

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