2011年1月14日金曜日

chromothripsisなる新しい概念が提唱されたよ。

























癌化に伴うゲノムの改変は普遍的におこるイベントとして認知されている。そしてこれは長年かかってゆっくり起こってくるものと考えられていた。しかしある種の腫瘍ではこの改変が、少なくとも一染色体レベルの改変なら数十から数百の断片化を経て一挙に改変されてしまうという驚くべき事実が報告された。


Cell, Volume 144, Issue 1, 27-40, 7 January 2011

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

Philip J. Stephens, Chris D. Greenman, Beiyuan Fu, Fengtang Yang, Graham R. Bignell, Laura J. Mudie, Erin D. Pleasance, King Wai Lau, David Beare, Lucy A. Stebbings, Stuart McLaren, Meng-Lay Lin, David J. McBride, Ignacio Varela, Serena Nik-Zainal, Catherine Leroy, Mingming Jia, Andrew Menzies, Adam P. Butler, Jon W. Teague, Michael A. Quail, John Burton, Harold Swerdlow, Nigel P. Carter, Laura A. Morsberger, Christine Iacobuzio-Donahue, George A. Follows, Anthony R. Green, Adrienne M. Flanagan, Michael R. Stratton, P. Andrew Futreal, Peter J. Campbell

Summary

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.

chromothripsis: Genomic features imply chromosome breaks occur in one-off crisis (“chromothripsis”)

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