A comprehensive catalogue of somatic mutations from a human cancer genome

Nature. 2010 Jan 14;463(7278):191-6. doi: 10.1038/nature08658. Epub 2009 Dec 16.


All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line, Tumor
  • DNA Damage / genetics
  • DNA Mutational Analysis
  • DNA Repair / genetics
  • Gene Dosage / genetics
  • Genes, Neoplasm / genetics*
  • Genome, Human / genetics*
  • Humans
  • Loss of Heterozygosity / genetics
  • Male
  • Melanoma / etiology
  • Melanoma / genetics
  • MicroRNAs / genetics
  • Mutagenesis, Insertional / genetics
  • Mutation / genetics*
  • Neoplasms / etiology
  • Neoplasms / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Precision Medicine
  • Sequence Deletion / genetics
  • Ultraviolet Rays


  • MicroRNAs