Publication Title
Cancer cell
Document Type
Article
Publication Date
8-14-2017
Keywords
Biomarkers, Tumor; DNA Copy Number Variations; DNA Methylation; Eukaryotic Initiation Factor-1; Gene Expression Regulation, Neoplastic; Humans; Melanoma; Monosomy; Mutation; Phosphoproteins; Prognosis; RNA Splicing Factors; Serine-Arginine Splicing Factors; Tumor Suppressor Proteins; Ubiquitin Thiolesterase; Uveal Neoplasms
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.
Clinical Institute
Cancer
Specialty/Research Institute
Oncology
Specialty/Research Institute
Institute for Systems Biology
