The landscape of cancer genes and mutational processes in breast cancer

Philip J. Stephens, Patrick S. Tarpey, Helen Davies, Peter Van Loo, Chris Greenman, David C. Wedge, Serena Nik Zainal, Sancha Martin, Ignacio Varela, Graham R. Bignell, Lucy R. Yates, Elli Papaemmanuil, David Beare, Adam Butler, Angela Cheverton, John Gamble, Jonathan Hinton, Mingming Jia, Alagu Jayakumar, David JonesCalli Latimer, King Wai Lau, Stuart McLaren, David J. McBride, Andrew Menzies, Laura Mudie, Keiran Raine, Roland Rad, Michael Spencer Chapman, Jon Teague, Douglas Easton, Anita Langerød, The Oslo Breast Cancer Consortium (OSBREAC), Ming Ta Michael Lee, Chen-Yang Shen, Benita Tan Kiat Tee, Bernice Wong Huimin, Annegien Broeks, Ana Cristina Vargas, Gulisa Turashvili, John Martens, Aquila Fatima, Penelope Miron, Suet-Feung Chin, Gilles Thomas, Sandrine Boyault, Odette Mariani, Sunil R. Lakhani, Marc van de Vijver, Laura van't Veer, John Foekens, Christine Desmedt, Christos Sotiriou, Andrew Tutt, Carlos Caldas, Jorge S. Reis-Filho, Samuel A. J. R. Aparicio, Anne Vincent Salomon, Anne-Lise Børresen-Dale, Andrea L. Richardson, Peter J. Campbell, P. Andrew Futreal, Michael R. Stratton

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1400 Citations (Scopus)


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 oncogenesis1, 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.
Original languageEnglish
Pages (from-to)400–404
Number of pages5
Issue number7403
Early online date16 May 2012
Publication statusPublished - 21 Jun 2012

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