Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Stephens PJ

PROVIDER: S-EPMC3065307 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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

Stephens Philip J PJ Greenman Chris D CD Fu Beiyuan B Yang Fengtang F Bignell Graham R GR Mudie Laura J LJ Pleasance Erin D ED Lau King Wai KW Beare David D Stebbings Lucy A LA McLaren Stuart S Lin Meng-Lay ML McBride David J DJ Varela Ignacio I Nik-Zainal Serena S Leroy Catherine C Jia Mingming M Menzies Andrew A Butler Adam P AP Teague Jon W JW Quail Michael A MA Burton John J Swerdlow Harold H Carter Nigel P NP Morsberger Laura A LA Iacobuzio-Donahue Christine C Follows George A GA Green Anthony R AR Flanagan Adrienne M AM Stratton Michael R MR Futreal P Andrew PA Campbell Peter J PJ

Cell 20110101 1

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 ...[more]

PMID: 21215367

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Dataset Information

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

Publications

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

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