Journal article
A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma
S Yokoyama, SL Woods, GM Boyle, LG Aoude, S MacGregor, V Zismann, M Gartside, AE Cust, R Haq, M Harland, JC Taylor, DL Duffy, K Holohan, K Dutton-Regester, JM Palmer, V Bonazzi, MS Stark, J Symmons, MH Law, C Schmidt Show all
Nature | Published : 2011
DOI: 10.1038/nature10630
Abstract
So far, two genes associated with familial melanoma have been identified, accounting for a minority of genetic risk in families. Mutations in CDKN2A account for approximately 40% of familial cases, and predisposing mutations in CDK4 have been reported in a very small number of melanoma kindreds. Here we report the whole-genome sequencing of probands from several melanoma families, which we performed in order to identify other genes associated with familial melanoma. We identify one individual carrying a novel germline variant (coding DNA sequence c.G1075A; protein sequence p.E318K; rs149617956) in the melanoma-lineage-specific oncogene microphthalmia-associated transcription factor (MITF). A..
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Awarded by Melanoma Research Alliance
Funding Acknowledgements
This work was supported by team science awards by the Melanoma Research Alliance (J.M.T., N.K.H., H. T. and D. E. F.), the American Cancer Society (K. M. B., RSG-08-200-01), the National Institutes of Health (NIH; D. E. F., AR043369-14; N.K.H., CA88363; H. T., K24CA149202 and P50CA93683), Doris Duke Medical Foundation (D. E. F.), Dr Miriam and Sheldon G. Adelson Medical Research Foundation (D. E. F.), US-Israel Binational Science Foundation (D. E. F.), and the Division of Cancer Epidemiology and Genetics of the National Cancer Institute (K. M. B.). N.K.H., D. L. D., S. M. and G. W. M. are supported by National Health and Medical Research Council of Australia (NHMRC) research fellowships. M. H. L. is supported by Cancer Australia grant 1011143. The collection of samples in the Leeds-based case-control study (the Melanoma Cohort Study) was funded by Cancer Research UK (Project Grant C8216/A6129 and Programme awards C588/A4994 and C588/A10589) and by the NIH (R01 CA83115). Recruitment was facilitated by the UK National Cancer Research Network. We thank S. Leake, S. Haynes, S. Waseem for Leeds case-control data collection; and H. Snowdon and C. Taylor from the Leeds Cancer Research UK Cancer Centre Genomics Facility for the genotyping of the UK samples. AMFS was supported by the NHMRC (project grants 566946, 107359, 211172 and program grant number 402761 to G.J.M. and R. F. K.); the Cancer Council New South Wales (project grant 77/00, 06/10), the Cancer Council Victoria and the Cancer Council Queensland (project grant 371); and the NIH (via RO1 grant CA-83115-01A2 to the international Melanoma Genetics Consortium-GenoMEL). The University of Cambridge SEARCH study was supported by Cancer Research UK Programme awards (C490/A11021 and C8197/A10123). A. E. C. is the recipient of an NHMRC public health postdoctoral fellowship (520018) and a Cancer Institute NSW Early Career Development Fellowship (10/ECF/2-06). B. K. A. is supported by a University of Sydney Medical Foundation Program Grant and J.L.H. is an Australia Fellow of the NHMRC. We gratefully acknowledge all of the participants, the work and dedication of the research coordinators, interviewers, examiners and data management staff, including J. Arbuckle, S. Columbus, M. Lang, H. Rodais, C. Ellis (Centre for MEGA Epidemiology); E. A. Holland, C. Agha-Hamilton, C. El Hayek, L. Morgan, J. Roland, E. Tyler, J. Barton, C. Watts and L. Porter (Westmead Institute of Cancer Research); M. Hillcoat, K. Holland, P. Saunders, J. Roberts and S. Tait (Viertel Centre for Research in Cancer Control); A. Kurien, C. Patterson, C. Thoo, S. de Zwaan, A. Sklavos, S. Manoharan, J. Cahill and S. Brennand (skin examiners).