The landscape of cancer genes and mutational processes in breast cancer

• Published in: Nature (London) Vol. 486; no. 7403; pp. 400 - 404
• Main Authors: Stephens, Philip J., Tarpey, Patrick S., Davies, Helen, Van Loo, Peter, Greenman, Chris, Wedge, David C., Nik-Zainal, Serena, Martin, Sancha, Varela, Ignacio, Bignell, Graham R., Yates, Lucy R., Papaemmanuil, Elli, Beare, David, Butler, Adam, Cheverton, Angela, Gamble, John, Hinton, Jonathan, Jia, Mingming, Jayakumar, Alagu, Jones, David, Latimer, Calli, Lau, King Wai, McLaren, Stuart, McBride, David J., Menzies, Andrew, Mudie, Laura, Raine, Keiran, Rad, Roland, Spencer Chapman, Michael, Teague, Jon, Easton, Douglas, Langerød, Anita, Lee, Ming Ta Michael, Shen, Chen-Yang, Tee, Benita Tan Kiat, Huimin, Bernice Wong, Broeks, Annegien, Vargas, Ana Cristina, Turashvili, Gulisa, Martens, John, Fatima, Aquila, Miron, Penelope, Chin, Suet-Feung, Thomas, Gilles, Boyault, Sandrine, Mariani, Odette, Lakhani, Sunil R., van de Vijver, Marc, van ‘t Veer, Laura, Foekens, John, Desmedt, Christine, Sotiriou, Christos, Tutt, Andrew, Caldas, Carlos, Reis-Filho, Jorge S., Aparicio, Samuel A. J. R., Salomon, Anne Vincent, Børresen-Dale, Anne-Lise, Richardson, Andrea L., Campbell, Peter J., Futreal, P. Andrew, Stratton, Michael R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.05.2012; Nature Publishing Group
• Subjects: 631/208/737; 631/67/395; 631/67/69; 692/699/67/1347; Age Factors; Biological and medical sciences; Breast cancer; Breast Neoplasms - classification; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Transformation, Neoplastic - genetics; Cytosine - metabolism; DNA Mutational Analysis; Female; Genes; Genetic diversity; Gynecology. Andrology. Obstetrics; Humanities and Social Sciences; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; Kinases; letter; Mammary gland diseases; Medical sciences; multidisciplinary; Mutagenesis - genetics; Mutation; Mutation - genetics; Neoplasm Grading; Oncogenes - genetics; Proteins; Reproducibility of Results; Science; Science (multidisciplinary); Signal Transduction - genetics; Tumors; Histological grading; Human; Breast disease; Breast cancer; Malignant tumor; Somatic mutation; Mammary gland diseases; Anatomic pathology; Cancerology; Histopathology; Gene; Number; Genetics; Diagnosis; Age; Cancer
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature11017

A study of breast cancers shows that the number of somatic mutations in each varies markedly and is strongly correlated with age at diagnosis and cancer histological grade. Variation in mutated breast cancer genes An analysis of mutated genes associated with breast cancer sampled from 100 patients reveals a wide variation in the number of mutations between individuals, highlighting the substantial genetic diversity underlying this disease. The mutation number correlates with age of diagnosis and histological grade. Multiple mutational signatures are identified, as are driver mutations in novel cancer genes. 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.