Publication Date:
2012-06-23
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428862/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428862/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- Chapman, Michael Spencer -- Teague, Jon -- Easton, Douglas -- Langerod, Anita -- Oslo Breast Cancer Consortium (OSBREAC) -- 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 -- Borresen-Dale, Anne-Lise -- Richardson, Andrea L -- Campbell, Peter J -- Futreal, P Andrew -- Stratton, Michael R -- 077012/Z/05/Z/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- 093867/Wellcome Trust/United Kingdom -- 10118/Cancer Research UK/United Kingdom -- CA089393/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- WT088340MA/Wellcome Trust/United Kingdom -- Cancer Research UK/United Kingdom -- Chief Scientist Office/United Kingdom -- Department of Health/United Kingdom -- England -- Nature. 2012 May 16;486(7403):400-4. doi: 10.1038/nature11017.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722201" target="_blank"〉PubMed〈/a〉
Keywords:
Age Factors
;
Breast Neoplasms/classification/*genetics/pathology
;
Cell Transformation, Neoplastic/*genetics
;
Cytosine/metabolism
;
DNA Mutational Analysis
;
Female
;
Humans
;
JNK Mitogen-Activated Protein Kinases/metabolism
;
Mutagenesis/*genetics
;
Mutation/*genetics
;
Neoplasm Grading
;
Oncogenes/*genetics
;
Reproducibility of Results
;
Signal Transduction/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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