Massive genomic rearrangement acquired in a single catastrophic event during cancer development

Stephens, Philip J., Greenman, Chris D., Fu, Beiyuan, Yang, Fengtang, Bignell, Graham R., Mudie, Laura J., Pleasance, Erin D., Lau, King Wai, Beare, David, Stebbings, Lucy A., McLaren, Stuart, Lin, Meng-Lay, McBride, David J., Varela, Ignacio, Nik-Zainal, Serena, Leroy, Catherine, Jia, Mingming, Menzies, Andrew, Butler, Adam P., Teague, Jon W., Quail, Michael A., Burton, John, Swerdlow, Harold, Carter, Nigel P., Morsberger, Laura A., Iacobuzio-Donahue, Christine, Follows, George A., Green, Anthony R., Flanagan, Adrienne M., Stratton, Michael R., Futreal, P. Michael and Campbell, Peter J. (2011) Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell, 144 (1). pp. 27-40. ISSN 0092-8674

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

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Computing Sciences

UEA Research Groups: Faculty of Science > Research Groups > Computational Biology
Depositing User: Christopher Greenman
Date Deposited: 22 Jun 2011 10:56
Last Modified: 21 Apr 2023 06:32
DOI: 10.1016/j.cell.2010.11.055

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