Document Type

Article

Publication Date

8-14-2017

Publication Title

Cancer cell

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

Department

Oncology

Department

Institute for Systems Biology

Included in

Oncology Commons

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