The landscape of cancer genes and mutational processes in breast cancer

Abstract

All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.

Keywords

Affiliated Institutions

• The Netherlands Cancer Institute NL
• Institute of Biomedical Sciences, Academia Sinica TW
• Université Libre de Bruxelles BE
• University of Cambridge GB
• King's College London GB
• Institute of Cancer Research GB
• Royal Brisbane and Women's Hospital AU
• Amsterdam UMC Location University of Amsterdam NL
• Singapore General Hospital SG
• Breast Cancer Now GB
• University of British Columbia CA
• University of Oslo
• Erasmus MC NL
• Université Claude Bernard Lyon 1 FR
• Addenbrooke's Hospital GB
• Centre Léon Bérard FR
• Oslo University Hospital
• The University of Queensland AU
• Cancer Research UK GB
• Institut Curie FR
• National Cancer Centre Singapore SG
• MRC Epidemiology Unit GB
• Guy's Hospital GB
• Dana-Farber Cancer Institute US
• Wellcome Sanger Institute GB

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