Signatures of mutation and selection in the cancer genome

Bignell, Graham R., Greenman, Chris D., Davies, Helen, Butler, Adam P., Edkins, Sarah, Andrews, Jenny M., Buck, Gemma, Chen, Lina, Beare, David, Latimer, Calli, Widaa, Sara, Hinton, Jonathon, Fahey, Ciara, Fu, Beiyuan, Swamy, Sajani, Dalgliesh, Gillian L., Teh, Bin T., Deloukas, Panos, Yang, Fengtang, Campbell, Peter J., Futreal, P. Andrew and Stratton, Michael R. (2010) Signatures of mutation and selection in the cancer genome. Nature, 463 (7283). pp. 893-898. ISSN 1476-4687

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Abstract

The cancer genome is moulded by the dual processes of somatic mutation and selection. Homozygous deletions in cancer genomes occur over recessive cancer genes, where they can confer selective growth advantage, and over fragile sites, where they are thought to reflect an increased local rate of DNA breakage. However, most homozygous deletions in cancer genomes are unexplained. Here we identified 2,428 somatic homozygous deletions in 746 cancer cell lines. These overlie 11% of protein-coding genes that, therefore, are not mandatory for survival of human cells. We derived structural signatures that distinguish between homozygous deletions over recessive cancer genes and fragile sites. Application to clusters of unexplained homozygous deletions suggests that many are in regions of inherent fragility, whereas a small subset overlies recessive cancer genes. The results illustrate how structural signatures can be used to distinguish between the influences of mutation and selection in cancer genomes. The extensive copy number, genotyping, sequence and expression data available for this large series of publicly available cancer cell lines renders them informative reagents for future studies of cancer biology and drug discovery.

Item Type:	Article
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Computing Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Computational Biology
Depositing User:	Christopher Greenman
Date Deposited:	22 Jun 2011 10:58
Last Modified:	22 Apr 2023 00:12
URI:	https://ueaeprints.uea.ac.uk/id/eprint/30586
DOI:	10.1038/nature08768

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