Genomic Classification of Cutaneous Melanoma

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, Pam Bartlett, Boris C. Bastian, Stephen B. Baylin, Madhusmita Behera, Dmitry BelyaevChristopher Benz, Brady Bernard, Rameen Beroukhim, Natalie Bir, Aaron D. Black, Tom Bodenheimer, Lori Boice, Genevieve M. Boland, Riccardo Bono, Moiz S. Bootwalla, Marcus Bosenberg, Jay Bowen, Reanne Bowlby, Christopher A. Bristow, Laura Brockway-Lunardi, Denise Brooks, Jakub Brzezinski, Wiam Bshara, Elizabeth Buda, William R. Burns, Yaron S.N. Butterfield, Michael Button, Tiffany Calderone, Giancarlo Antonini Cappellini, Candace Carter, Scott L. Carter, Lynn Cherney, Andrew D. Cherniack, Aaron Chevalier, Lihua Zou, The Cancer Genome Atlas Network

Research output: Contribution to journalArticlepeer-review

1224 Scopus citations

Abstract

Summary 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.

Original languageEnglish (US)
Pages (from-to)1681-1696
Number of pages16
JournalCell
Volume161
Issue number7
DOIs
StatePublished - Jun 20 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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