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

doi:10.1016/j.cell.2010.11.055

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. TeagueMichael 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

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1420 Scopus citations

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. PaperClip:

Original language	English (US)
Pages (from-to)	27-40
Number of pages	14
Journal	Cell
Volume	144
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2010.11.055
State	Published - Jan 7 2011
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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Stephens, P. J., Greenman, C. D., Fu, B., Yang, F., Bignell, G. R., Mudie, L. J., Pleasance, E. D., Lau, K. W., Beare, D., Stebbings, L. A., McLaren, S., Lin, M. L., McBride, D. J., Varela, I., Nik-Zainal, S., Leroy, C., Jia, M., Menzies, A., Butler, A. P., ... Campbell, P. J. (2011). Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell, 144(1), 27-40. https://doi.org/10.1016/j.cell.2010.11.055

Stephens, PJ, Greenman, CD, Fu, B, Yang, F, Bignell, GR, Mudie, LJ, Pleasance, ED, Lau, KW, Beare, D, Stebbings, LA, McLaren, S, Lin, ML, McBride, DJ, Varela, I, Nik-Zainal, S, Leroy, C, Jia, M, Menzies, A, Butler, AP, Teague, JW, Quail, MA, Burton, J, Swerdlow, H, Carter, NP, Morsberger, LA, Iacobuzio-Donahue, C, Follows, GA, Green, AR, Flanagan, AM, Stratton, MR, Futreal, PA & Campbell, PJ 2011, 'Massive genomic rearrangement acquired in a single catastrophic event during cancer development', Cell, vol. 144, no. 1, pp. 27-40. https://doi.org/10.1016/j.cell.2010.11.055

@article{2934af222a6b4d5693006362fad8d60c,

title = "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. PaperClip:",

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

note = "Funding Information: This work was supported by the Wellcome Trust (grant reference 077012/Z/05/Z) and the Chordoma Foundation. P.J.C. is personally funded through a Wellcome Trust Senior Clinical Research Fellowship (grant reference WT088340MA). I.V. is supported by a fellowship from The International Human Frontier Science Program Organization. We also acknowledge support for sample banking and processing from the Cambridge and UCL/UCLH NIHR Biomedical Research Centres and Skeletal Action Cancer Trust (SCAT), especially Dr. Anthony Bench, Dr. Wendy Erber, and Miss Dina Halai. We would like to thank George Vassiliou for the neologism “chromothripsis.” ",

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doi = "10.1016/j.cell.2010.11.055",

language = "English (US)",

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T1 - Massive genomic rearrangement acquired in a single catastrophic event during cancer development

AU - Stephens, Philip J.

AU - Greenman, Chris D.

AU - Fu, Beiyuan

AU - Yang, Fengtang

AU - Bignell, Graham R.

AU - Mudie, Laura J.

AU - Pleasance, Erin D.

AU - Lau, King Wai

AU - Beare, David

AU - Stebbings, Lucy A.

AU - McLaren, Stuart

AU - Lin, Meng Lay

AU - McBride, David J.

AU - Varela, Ignacio

AU - Nik-Zainal, Serena

AU - Leroy, Catherine

AU - Jia, Mingming

AU - Menzies, Andrew

AU - Butler, Adam P.

AU - Teague, Jon W.

AU - Quail, Michael A.

AU - Burton, John

AU - Swerdlow, Harold

AU - Carter, Nigel P.

AU - Morsberger, Laura A.

AU - Iacobuzio-Donahue, Christine

AU - Follows, George A.

AU - Green, Anthony R.

AU - Flanagan, Adrienne M.

AU - Stratton, Michael R.

AU - Futreal, P. Andrew

AU - Campbell, Peter J.

N1 - Funding Information: This work was supported by the Wellcome Trust (grant reference 077012/Z/05/Z) and the Chordoma Foundation. P.J.C. is personally funded through a Wellcome Trust Senior Clinical Research Fellowship (grant reference WT088340MA). I.V. is supported by a fellowship from The International Human Frontier Science Program Organization. We also acknowledge support for sample banking and processing from the Cambridge and UCL/UCLH NIHR Biomedical Research Centres and Skeletal Action Cancer Trust (SCAT), especially Dr. Anthony Bench, Dr. Wendy Erber, and Miss Dina Halai. We would like to thank George Vassiliou for the neologism “chromothripsis.”

PY - 2011/1/7

Y1 - 2011/1/7

N2 - 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. PaperClip:

AB - 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. PaperClip:

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

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