A comprehensive catalogue of somatic mutations from a human cancer genome

Erin D. Pleasance, R. Keira Cheetham, Philip J. Stephens, David J. Mcbride, Sean J. Humphray, Christopher Greenman, Ignacio Varela, Meng-Lay Lin, Gonzalo R. Ordóñez, Graham R. Bignell, Kai Ye, Julie Alipaz, Markus J. Bauer, David Beare, Adam Butler, Richard J. Carter, Lina Chen, Anthony J. Cox, Sarah Edkins, Paula I. Kokko-GonzalesNiall A. Gormley, Russell J. Grocock, Christian D. Haudenschild, Matthew M. Hims, Terena James, Mingming Jia, Zoya Kingsbury, Catherine Leroy, John Marshall, Andrew Menzies, Laura J. Mudie, Zemin Ning, Tom Royce, Ole B. Schulz-Trieglaff, Anastassia Spiridou, Lucy A. Stebbings, Lukasz Szajkowski, Jon Teague, David Williamson, Lynda Chin, Mark T. Ross, Peter J. Campbell, David R. Bentley, P. Andrew Futreal, Michael R. Stratton

Research output: Contribution to journalArticlepeer-review

1350 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)191-196
Number of pages6
Issue number7278
Publication statusPublished - 14 Jan 2010

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