Genomic Classification of Cutaneous Melanoma.

Cancer Genome Atlas Network
Cell. 2015 161 (7): 1681-96

PMID: 26091043 · PMCID: PMC4580370 · DOI:10.1016/j.cell.2015.05.044

We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.

Copyright © 2015 Elsevier Inc. All rights reserved.

MeSH Terms (7)

Databases, Genetic Humans Melanoma Mutation National Cancer Institute (U.S.) Skin Neoplasms United States

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