Mutational processes molding the genomes of 21 breast cancers

Nik-Zainal, S. et al. (2012) Mutational processes molding the genomes of 21 breast cancers. Cell, 149(5), pp. 979-993. (doi: 10.1016/j.cell.2012.04.024) (PMID:22608084) (PMCID:PMC3414841)

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All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed “kataegis,” was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed.

Item Type:Articles
Additional Information:The authors ... and the Breast Cancer Working Group of the International Cancer Genome Consortium.
Glasgow Author(s) Enlighten ID:Cooke, Dr Susie and Martin, Ms Sancha and Marshall, Mr John
Authors: Nik-Zainal, S., Alexandrov, L. B., Wedge, D. C., Van Loo, P., Greenman, C. D., Raine, K., Jones, D., Hinton, J., Marshall, J., Stebbings, L. A., Menzies, A., Martin, S., Leung, K., Chen, L., Leroy, C., Ramakrishna, M., Rance, R., Lau, K. W., Mudie, L. J., Varela, I., McBride, D. J., Bignell, G. R., Cooke, S. L., Shlien, A., Gamble, J., Whitmore, I., Maddison, M., Tarpey, P. S., Davies, H. R., Papaemmanuil, E., Stephens, P. J., McLaren, S., Butler, A. P., Teague, J. W., Jönsson, G., Garber, J. E., Silver, D., Miron, P., Fatima, A., Boyault, S., Langerød, A., Tutt, A., Martens, J. W.M., Aparicio, S. A.J.R., Borg, Å., Salomon, A. V., Thomas, G., Børresen-Dale, A.-L., Richardson, A. L., Neuberger, M. S., Futreal, P. A., Campbell, P. J., and Stratton, M. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cell
Publisher:Elsevier (Cell Press)
ISSN (Online):1097-4172
Published Online:17 May 2012
Copyright Holders:Copyright © 2012 Elsevier Inc.
First Published:First published in Cell 149(5):979-993
Publisher Policy:Reproduced under a Creative Commons License

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