作者
Michael Krauthammer, Yong Kong, Byung Hak Ha, Perry Evans, Antonella Bacchiocchi, Jamie P McCusker, Elaine Cheng, Matthew J Davis, Gerald Goh, Murim Choi, Stephan Ariyan, Deepak Narayan, Ken Dutton-Regester, Ana Capatana, Edna C Holman, Marcus Bosenberg, Mario Sznol, Harriet M Kluger, Douglas E Brash, David F Stern, Miguel A Materin, Roger S Lo, Shrikant Mane, Shuangge Ma, Kenneth K Kidd, Nicholas K Hayward, Richard P Lifton, Joseph Schlessinger, Titus J Boggon, Ruth Halaban
发表日期
2012/9
期刊
Nature genetics
卷号
44
期号
9
页码范围
1006-1014
出版商
Nature Publishing Group US
简介
We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1P29S) in the highly conserved switch I domain. Crystal structures, and biochemical and …
引用总数
学术搜索中的文章
M Krauthammer, Y Kong, BH Ha, P Evans… - Nature genetics, 2012