The landscape of cancer genes and mutational processes in breast cancer.


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.

DOI: 10.1038/nature11017

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@article{Stephens2012TheLO, title={The landscape of cancer genes and mutational processes in breast cancer.}, author={P. Stephens and P. Tarpey and H. Davies and Peter van Loo and C. Greenman and David C. Wedge and Serena Nik-Zainal and Sancha Martin and Ignacio Varela and Graham Bignell and Lucy R. Yates and Elli Papaemmanuil and David Beare and Adam P. Butler and Angela M. Cheverton and John Gamble and Jonathan W. Hinton and Mingming Jia and Alagu Jayakumar and David Jones and Calli Latimer and King Wai Lau and Stuart J. McLaren and D. J. McBride and Andrew Menzies and Laura J. Mudie and Keiran Raine and R. Rezai Rad and Michael Spencer Chapman and Jon W. Teague and Douglas F. Easton and Anita Langer\od and Ming Ta Michael Lee and Chen-yang Shen and Benita Tan Kiat Tee and Bernice Wong Huimin and Annegien Broeks and Ana Cristina Vargas and Gulisa Turashvili and John W M Martens and Aquila Fatima and Penelope L. Miron and Suet F Chin and Gilles D. Thomas and Sandrine Boyault and Odette Mariani and Sunil R Lakhani and Marc J. van de Vijver and Laura J van 't Veer and John A. Foekens and Christine Desmedt and Christos Sotiriou and Andrew N Tutt and Carlos Caldas and Jorge S Reis-Filho and Samuel Aparicio and Anne Vincent Salomon and Anne-Lise B\orresen-Dale and Andrea L. Richardson and Peter J. Campbell and P. Andrew Futreal and Michael R. Stratton}, journal={Nature}, year={2012}, volume={486 7403}, pages={400-4} }