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Genomic Classification of Cutaneous Melanoma

Journal article published in 2015 by Rehan Akbani, Kadir C. Akdemir, B. Arman Aksoy, Monique Albert, Adrian Ally, Samirkumar B. Amin, Harindra Arachchi, Arshi Arora, J. Todd Auman, Brenda Ayala, Julien Baboud, Miruna Balasundaram, Saianand Balu, Nandita Barnabas, John Bartlett and other authors.
This paper is available in a repository.
This paper is available in a repository.

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Abstract

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.