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dc.contributor.authorStratton, M
dc.date.accessioned2018-06-08T14:44:52Z
dc.date.issued2011-01
dc.identifier1
dc.identifier.citationCELL, 2011, 144 pp. 27 - 40
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1775
dc.description.abstractCancer 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.
dc.format.extent27 - 40
dc.languageeng
dc.language.isoeng
dc.titleMassive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development
dc.typeJournal Article
rioxxterms.licenseref.startdate2011-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCELL
pubs.notesISI Document Delivery No.: 703QF Times Cited: 1 Cited Reference Count: 36 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. Andrew Campbell, Peter J. Wellcome Trust [077012/Z/05/Z, WT088340MA]; Chordoma Foundation ; International Human Frontier Science Program Organization 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.” Cell press Cambridge keywords: cell lung-cancer pancreatic-cancer tumor-suppressor mutations evolution instability signatures resolution sequence
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Genetic Susceptibility
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Genetic Susceptibility
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Genetic Susceptibility
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Genetic Susceptibility
pubs.volume144en_US
pubs.embargo.termsNot known
pubs.oa-locationhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065307/
icr.researchteamGenetic Susceptibilityen_US
dc.contributor.icrauthorStratton, Michaelen


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