Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/143325
Title: | Whole-genome landscapes of major melanoma subtypes |
Author: | Hayward, Nicholas K. Wilmott, James S. Waddell, Nicola Johansson, Peter A. Field, Matthew A. Nones, Katia Patch, Ann-Marie Kakavand, Hojabr Alexandrov, Ludmil B. Burke, Hazel Jakrot, Valerie Kazakoff, Stephen Holmes, Oliver Leonard, Conrad Sabarinathan, Radhakrishnan Mularoni, Loris Wood, Scott Xu, Qinying Waddell, Nick Tembe, Varsha Pupo, Gulietta M. Paoli-Iseppi, Ricardo De Vilain, Ricardo E. Shang, Ping Lau, Loretta M.S. Dagg, Rebecca A. Schramm, Sarah-Jane Pritchard, Antonia Dutton-Regester, Ken Newell, Felicity Fitzgerald, Anna Shang, Catherine A. Grimmond, Sean M. Pickett, Hilda A. Yang, Jean Y. Stretch, Jonathan R. Behren, Andreas Kefford, Richard F. Hersey, Peter Long, Georgina V. Cebon, Jonathan Shackleton, Mark Spillane, Andrew J. Saw, Robyn P. M. López Bigas, Núria Pearson, John V. Thompson, John F. Scolyer, Richard A. Mann, Graham J. |
Keywords: | Melanoma Càncer Cancer |
Issue Date: | 3-May-2017 |
Publisher: | Springer |
Abstract: | Melanoma of the skin is a common cancer only in Europeans, whereas it arises in internal body surfaces (mucosal sites) and on the hands and feet (acral sites) in people throughout the world. Here we report analysis of whole-genome sequences from cutaneous, acral and mucosal subtypes of melanoma. The heavily mutated landscape of coding and non-coding mutations in cutaneous melanoma resolved novel signatures of mutagenesis attributable to ultraviolet radiation. However, acral and mucosal melanomas were dominated by structural changes and mutation signatures of unknown aetiology, not previously identified in melanoma. The number of genes affected by recurrent mutations disrupting non-coding sequences was similar to that affected by recurrent mutations to coding sequences. Significantly mutated genes included BRAF, CDKN2A, NRAS and TP53 in cutaneous melanoma, BRAF, NRAS and NF1 in acral melanoma and SF3B1 in mucosal melanoma. Mutations affecting the TERT promoter were the most frequent of all; however, neither they nor ATRX mutations, which correlate with alternative telomere lengthening, were associated with greater telomere length. Most melanomas had potentially actionable mutations, most in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways. The whole-genome mutation landscape of melanoma reveals diverse carcinogenic processes across its subtypes, some unrelated to sun exposure, and extends potential involvement of the non-coding genome in its pathogenesis. |
Note: | Versió postprint del document publicat a: http://dx.doi.org/10.1038/nature22071 |
It is part of: | Nature, 2017, vol. 545, num. 7653, p. 175-180 |
URI: | http://hdl.handle.net/2445/143325 |
Related resource: | http://dx.doi.org/10.1038/nature22071 |
Appears in Collections: | Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) Publicacions de projectes de recerca finançats per la UE |
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File | Description | Size | Format | |
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melanomagenome-finalplusfigsauthors.pdf | 5.42 MB | Adobe PDF | View/Open |
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