1. Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
2. EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
3. Molecular Pathology Unit, Neurosurgical Service and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
4. Royal Brompton Hospital, London SW3 6NP, UK
5. Ludwig Institute for Cancer Research, 1200 Brussels, Belgium
6. 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
7. University of Pennsylvania Cancer Centre, Philadelphia, Pennsylvania 19104-6160, USA
8. Department of Gynaecological Oncology, Westmead Hospital and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead NSW 2145, Australia
9. Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
10. Department of Haematology, Addenbrooke's NHS Trust and University of Cambridge, Cambridge CB2 0QQ, UK
11. Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge CB1 8RN, UK
12. Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Queensland 4029, Australia
13. Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
14. Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong

Correspondence to: P. Andrew Futreal¹Michael R. Stratton^1,9 Correspondence and requests for materials should be addressed to P.A.F. (Email: paf@sanger.ac.uk) or M.R.S. (Email: mrs@sanger.ac.uk).

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.

1. Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
2. EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
3. Molecular Pathology Unit, Neurosurgical Service and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
4. Royal Brompton Hospital, London SW3 6NP, UK
5. Ludwig Institute for Cancer Research, 1200 Brussels, Belgium
6. 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
7. University of Pennsylvania Cancer Centre, Philadelphia, Pennsylvania 19104-6160, USA
8. Department of Gynaecological Oncology, Westmead Hospital and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead NSW 2145, Australia
9. Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
10. Department of Haematology, Addenbrooke's NHS Trust and University of Cambridge, Cambridge CB2 0QQ, UK
11. Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge CB1 8RN, UK
12. Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Queensland 4029, Australia
13. Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
14. Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong

Correspondence to: P. Andrew Futreal¹Michael R. Stratton^1,9 Correspondence and requests for materials should be addressed to P.A.F. (Email: paf@sanger.ac.uk) or M.R.S. (Email: mrs@sanger.ac.uk).

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