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Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma.

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.

SUBMITTER: Robertson AG 

PROVIDER: S-EPMC5619925 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma.

Robertson A Gordon AG   Shih Juliann J   Yau Christina C   Gibb Ewan A EA   Oba Junna J   Mungall Karen L KL   Hess Julian M JM   Uzunangelov Vladislav V   Walter Vonn V   Danilova Ludmila L   Lichtenberg Tara M TM   Kucherlapati Melanie M   Kimes Patrick K PK   Tang Ming M   Penson Alexander A   Babur Ozgun O   Akbani Rehan R   Bristow Christopher A CA   Hoadley Katherine A KA   Iype Lisa L   Chang Matthew T MT   Cherniack Andrew D AD   Benz Christopher C   Mills Gordon B GB   Verhaak Roel G W RGW   Griewank Klaus G KG   Felau Ina I   Zenklusen Jean C JC   Gershenwald Jeffrey E JE   Schoenfield Lynn L   Lazar Alexander J AJ   Abdel-Rahman Mohamed H MH   Roman-Roman Sergio S   Stern Marc-Henri MH   Cebulla Colleen M CM   Williams Michelle D MD   Jager Martine J MJ   Coupland Sarah E SE   Esmaeli Bita B   Kandoth Cyriac C   Woodman Scott E SE  

Cancer cell 20170801 2

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-f  ...[more]

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