Patterns of somatic mutation in human cancer genomes

Christopher Greenman, Philip Stephens, Raffaella Smith, Gillian L. Dalgliesh, Christopher Hunter, Graham Bignell, Helen Davies, Jon Teague, Adam Butler, Claire Stevens, Sarah Edkins, Sarah O’Meara, Imre Vastrik, Esther E. Schmidt, Tim Avis, Syd Barthorpe, Gurpreet Bhamra, Gemma Buck, Bhudipa Choudhury, Jody Clements, Jennifer Cole, Ed Dicks, Simon Forbes, Kris Gray, Kelly Halliday, Rachel Harrison, Katy Hills, Jon Hinton, Andy Jenkinson, David Jones, Andy Menzies, Tatiana Mironenko, Janet Perry, Keiran Raine, Dave Richardson, Rebecca Shepherd, Alexandra Small, Calli Tofts, Jennifer Varian, Tony Webb, Sofie West, Sara Widaa, Andy Yates, Daniel P. Cahill, David N. Louis, Peter Goldstraw, Andrew G. Nicholson, Francis Brasseur, Leendert Looijenga, Barbara L. Weber, Yoke-Eng Chiew, Anna deFazio, Mel F. Greaves, Anthony R. Green, Peter Campbell, Ewan Birney, Douglas F. Easton, Georgia Chenevix-Trench, Min-Han Tan, Sok Kean Khoo, Bin Tean Teh, Siu Tsan Yuen, Suet Yi Leung, Richard Wooster, P. Andrew Futreal () and Michael R. Stratton ()
Additional contact information
Christopher Greenman: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Philip Stephens: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Raffaella Smith: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Gillian L. Dalgliesh: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Christopher Hunter: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Graham Bignell: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Helen Davies: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Jon Teague: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Adam Butler: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Claire Stevens: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Sarah Edkins: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Sarah O’Meara: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Imre Vastrik: EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
Esther E. Schmidt: EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
Tim Avis: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Syd Barthorpe: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Gurpreet Bhamra: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Gemma Buck: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Bhudipa Choudhury: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Jody Clements: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Jennifer Cole: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Ed Dicks: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Simon Forbes: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Kris Gray: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Kelly Halliday: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Rachel Harrison: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Katy Hills: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Jon Hinton: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Andy Jenkinson: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
David Jones: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Andy Menzies: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Tatiana Mironenko: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Janet Perry: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Keiran Raine: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Dave Richardson: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Rebecca Shepherd: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Alexandra Small: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Calli Tofts: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Jennifer Varian: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Tony Webb: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Sofie West: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Sara Widaa: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Andy Yates: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Daniel P. Cahill: Molecular Pathology Unit, Neurosurgical Service and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
David N. Louis: Molecular Pathology Unit, Neurosurgical Service and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
Peter Goldstraw: Royal Brompton Hospital, London SW3 6NP, UK
Andrew G. Nicholson: Royal Brompton Hospital, London SW3 6NP, UK
Francis Brasseur: Ludwig Institute for Cancer Research, 1200 Brussels, Belgium
Leendert Looijenga: Laboratory of Pathology/Experimental Patho-Oncology, Erasmus MC University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Josephine Nefkens Institute, 3000 DR Rotterdam, UCL 745, B-1200, The Netherlands
Barbara L. Weber: University of Pennsylvania Cancer Centre, Philadelphia, Pennsylvania 19104-6160, USA
Yoke-Eng Chiew: Westmead Hospital and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead NSW 2145, Australia
Anna deFazio: Westmead Hospital and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead NSW 2145, Australia
Mel F. Greaves: Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
Anthony R. Green: Addenbrooke’s NHS Trust and University of Cambridge, Cambridge CB2 0QQ, UK
Peter Campbell: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Ewan Birney: EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
Douglas F. Easton: Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge CB1 8RN, UK
Georgia Chenevix-Trench: Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Queensland 4029, Australia
Min-Han Tan: Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
Sok Kean Khoo: Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
Bin Tean Teh: Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
Siu Tsan Yuen: The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong
Suet Yi Leung: The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong
Richard Wooster: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
P. Andrew Futreal: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
Michael R. Stratton: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK

Nature, 2007, vol. 446, issue 7132, 153-158

Abstract: Abstract Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be ‘passengers’ that do not contribute to oncogenesis. However, there was evidence for ‘driver’ mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.

Date: 2007
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DOI: 10.1038/nature05610

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