| Literature DB >> 28810145 |
A Gordon Robertson1, Juliann Shih2, Christina Yau3, Ewan A Gibb1, Junna Oba4, Karen L Mungall1, Julian M Hess5, Vladislav Uzunangelov6, Vonn Walter7, Ludmila Danilova8, Tara M Lichtenberg9, Melanie Kucherlapati10, Patrick K Kimes11, Ming Tang12, Alexander Penson13, Ozgun Babur14, Rehan Akbani15, Christopher A Bristow16, Katherine A Hoadley17, Lisa Iype18, Matthew T Chang19, Andrew D Cherniack2, Christopher Benz3, Gordon B Mills20, Roel G W Verhaak21, Klaus G Griewank22, Ina Felau23, Jean C Zenklusen23, Jeffrey E Gershenwald24, Lynn Schoenfield25, Alexander J Lazar26, Mohamed H Abdel-Rahman27, Sergio Roman-Roman28, Marc-Henri Stern28, Colleen M Cebulla29, Michelle D Williams26, Martine J Jager30, Sarah E Coupland31, Bita Esmaeli32, Cyriac Kandoth33, Scott E Woodman34.
Abstract
Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.Entities:
Keywords: EIF1AX; GNA11; GNAQ; SF3B1; SRSF2; TCGA; molecular subtypes; monosomy 3; noncoding RNA; uveal melanoma
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Year: 2017 PMID： 28810145 PMCID： PMC5619925 DOI： 10.1016/j.ccell.2017.07.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743