학술논문
Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma
Document Type
article
Author
Robertson, A Gordon; Shih, Juliann; Yau, Christina; Gibb, Ewan A; Oba, Junna; Mungall, Karen L; Hess, Julian M; Uzunangelov, Vladislav; Walter, Vonn; Danilova, Ludmila; Lichtenberg, Tara M; Kucherlapati, Melanie; Kimes, Patrick K; Tang, Ming; Penson, Alexander; Babur, Ozgun; Akbani, Rehan; Bristow, Christopher A; Hoadley, Katherine A; Iype, Lisa; Chang, Matthew T; Network, TCGA Research; Abdel-Rahman, Mohamed H; Ally, Adrian; Auman, J Todd; Balasundaram, Miruna; Balu, Saianand; Benz, Christopher; Beroukhim, Rameen; Birol, Inanc; Bodenheimer, Tom; Bowen, Jay; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Cebulla, Colleen M; Cherniack, Andrew D; Chin, Lynda; Cho, Juok; Chuah, Eric; Chudamani, Sudha; Cibulskis, Carrie; Cibulskis, Kristian; Cope, Leslie; Coupland, Sarah E; Defreitas, Timothy; Demchok, John A; Desjardins, Laurence; Dhalla, Noreen; Esmaeli, Bita; Felau, Ina; Ferguson, Martin L; Frazer, Scott; Gabriel, Stacey B; Gastier-Foster, Julie M; Gehlenborg, Nils; Gerken, Mark; Gershenwald, Jeffrey E; Getz, Gad; Griewank, Klaus G; Grimm, Elizabeth A; Hayes, D Neil; Hegde, Apurva M; Heiman, David I; Helsel, Carmen; Hobensack, Shital; Holt, Robert A; Hoyle, Alan P; Hu, Xin; Hutter, Carolyn M; Jager, Martine J; Jefferys, Stuart R; Jones, Corbin D; Jones, Steven JM; Kandoth, Cyriac; Kasaian, Katayoon; Kim, Jaegil; Kucherlapati, Raju; Lander, Eric; Lawrence, Michael S; Lazar, Alexander J; Lee, Semin; Leraas, Kristen M; Lin, Pei; Liu, Jia; Liu, Wenbin; Lolla, Laxmi; Lu, Yiling
Source
Cancer Cell. 32(2)
Subject
Language
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.