title: Patterns of somatic mutation in human cancer genomes.
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.
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Christopher
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authors.lastname: Looijenga
authors.forename: Barbara L
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authors.lastname: Weber
authors.forename: Yoke-Eng
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authors.lastname: Chiew
authors.forename: Anna
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authors.lastname: DeFazio
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authors.lastname: Chenevix-Trench
authors.forename: Min-Han
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authors.lastname: Tan
authors.forename: Sok Kean
authors.initials: SK
authors.lastname: Khoo
authors.forename: Bin Tean
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authors.lastname: Teh
authors.forename: Siu Tsan
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authors.lastname: Yuen
authors.forename: Suet Yi
authors.initials: SY
authors.lastname: Leung
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authors.lastname: Wooster
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mesh_terms: D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D052138:Genes, Neoplasm / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; D011494:Protein Kinases