1. The landscape of cancer genes and mutational processes in breast cancer
- Author
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John W.M. Martens, Peter J. Campbell, Penelope Miron, David J. McBride, Sancha Martin, Ming Ta Michael Lee, Keiran Raine, King Wai Lau, Serena Nik-Zainal, Christopher Greenman, Michael R. Stratton, Carlos Caldas, Chen-Yang Shen, Marc J. van de Vijver, Jorge S. Reis-Filho, Laura van 't Veer, John Gamble, Aquila Fatima, Alagu Jayakumar, Gilles Thomas, Patrick S. Tarpey, Stuart McLaren, Ana Cristina Vargas, Graham R. Bignell, Elli Papaemmanuil, Andrea L. Richardson, Sandrine Boyault, Anita Langerød, Anne Lise Børresen-Dale, Suet-Feung Chin, Angela Cheverton, Christos Sotiriou, David C. Wedge, Bernice Wong Huimin, Adam Butler, Odette Mariani, Gulisa Turashvili, Christine Desmedt, Calli Latimer, Roland Rad, Douglas F. Easton, Samuel Aparicio, Jon W. Teague, Ignacio Varela, Anne Vincent Salomon, Michael Spencer Chapman, Andrew Tutt, Helen Davies, John A. Foekens, Peter Van Loo, Lucy R. Yates, David Jones, Philip J. Stephens, P. Andrew Futreal, Jonathan Hinton, L. Mudie, Sunil R. Lakhani, Annegien Broeks, Andrew Menzies, David Beare, Mingming Jia, Benita Tan Kiat Tee, Medical Oncology, Radiotherapy, CCA -Cancer Center Amsterdam, and Pathology
- Subjects
Genetics ,Mutation ,Multidisciplinary ,Cancer ,Biology ,medicine.disease ,medicine.disease_cause ,Somatic evolution in cancer ,Article ,Breast cancer ,Germline mutation ,SDG 3 - Good Health and Well-being ,DNA Mutational Analysis ,medicine ,Breast disease ,Carcinogenesis - 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(1), 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.
- Published
- 2012