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 ClementsJennifer 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, Michael R Stratton

Research output: Contribution to journalArticlepeer-review

2477 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)153-8
Number of pages6
JournalNature
Volume446
Issue number7132
DOIs
Publication statusPublished - 8 Mar 2007
Externally publishedYes

Keywords

  • Amino Acid Sequence
  • DNA Mutational Analysis
  • Genes, Neoplasm/genetics
  • Genome, Human/genetics
  • Genomics
  • Humans
  • Molecular Sequence Data
  • Mutation/genetics
  • Neoplasm Proteins/chemistry
  • Neoplasms/genetics
  • Protein Kinases/chemistry

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