Journal article
Genomic Classification of Cutaneous Melanoma
Cell, Vol.161(7), pp.1681-1696
Jun/2015
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 sub-types 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 multidimensional 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.
Details
- Title
- Genomic Classification of Cutaneous Melanoma
- Creators
- The Cancer Genome Atlas Network (Institution)Yardena Samuels (null) - 972WIS_INST___122
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.161(7), pp.1681-1696; Jun/2015
- Number of pages
- 16
- Language
- English
- DOI
- https://doi.org/10.1016/j.cell.2015.05.044
- Grant note
- We thank all patients and families who contributed to this study. We are grateful to Chris Gunter for manuscript editing and Ina Felau and Margi Sheth for project management. This article is dedicated to the memory of Donald L. Morton, M.D., a pioneer in melanoma oncology, who passed away on January 10, 2014. This study was supported by NIH grants: U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, and P30 CA016672.; A.D.C. and M.M. receive research funding from Bayer AG. M.M. is a founder of, equity holder in, and consultant for Foundation Medicine, a next-generation sequencing-based cancer diagnostics company. L.A.G. received a commercial research grant from Novartis and is a consultant/advisory board member for Novartis, Foundation Medicine, and Boehringer Ingelheim. L.A.G. also has equity interest in Foundation Medicine. D.J.W. is a consultant for Zymo Research Corporation, which distributes commercially available products for DNA methylation-based experiments. Zymo Research neither supported this work nor has an interest in the outcome of this research. O.P and O.V. are co-founders and shareholders of Cureline, Inc., which received a contract payment from the NIH for this work. J.E.G. is an advisory board member for Merck._ALMAME_DELIMITER_
- Record Identifier
- 993265018303596
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