Patterns of somatic mutation in human cancer genomes.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Greenman, C; Stephens, P; Smith, R; Dalgliesh, GL; Hunter, C; Bignell, G; Davies, H; Teague, J; Butler, A; Stevens, C; Edkins, S; O'Meara, S; Vastrik, I; Schmidt, EE; Avis, T; Barthorpe, S; Bhamra, G; Buck, G; Choudhury, B; Clements, J; Cole, J; Dicks, E; Forbes, S; Gray, K; Halliday, K; Harrison, R; Hills, K; Hinton, J; Jenkinson, A; Jones, D; Menzies, A; Mironenko, T; Perry, J; Raine, K; Richardson, D; Shepherd, R; Small, A; Tofts, C; Varian, J; Webb, T; West, S; Widaa, S; Yates, A; Cahill, DP; Louis, DN; Goldstraw, P; Nicholson, AG; Brasseur, F; Looijenga, L; Weber, BL; Chiew, Y-E; DeFazio, A; Greaves, MF; Green, AR; Campbell, P; Birney, E; Easton, DF; Chenevix-Trench, G; Tan, M-H; Khoo, SK; Teh, BT; Yuen, ST; Leung, SY; Wooster, R; Futreal, PA; Stratton, MR

Published Date

  • March 2007

Published In

Volume / Issue

  • 446 / 7132

Start / End Page

  • 153 - 158

PubMed ID

  • 17344846

Pubmed Central ID

  • 17344846

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature05610

Language

  • eng