Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

Authors:
Dr Lucy Yates, MA MBBS PhD
Dr Lucy Yates, MA MBBS PhD
Wellcome Trust Sanger Institute
Dr
Clinical Oncology, Cancer Genomics
Cambridge | United Kingdom

Nature 2016 06 2;534(7605):47-54. Epub 2016 May 2.

Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.

We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.

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http://dx.doi.org/10.1038/nature17676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910866PMC
June 2016
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