학술논문
Genomic Classification of Cutaneous Melanoma
Document Type
article
Author
Network, The Cancer Genome Atlas; Akbani, Rehan; Akdemir, Kadir C; Aksoy, B Arman; Albert, Monique; Ally, Adrian; Amin, Samirkumar B; Arachchi, Harindra; Arora, Arshi; Auman, J Todd; Ayala, Brenda; Baboud, Julien; Balasundaram, Miruna; Balu, Saianand; Barnabas, Nandita; Bartlett, John; Bartlett, Pam; Bastian, Boris C; Baylin, Stephen B; Behera, Madhusmita; Belyaev, Dmitry; Benz, Christopher; Bernard, Brady; Beroukhim, Rameen; Bir, Natalie; Black, Aaron D; Bodenheimer, Tom; Boice, Lori; Boland, Genevieve M; Bono, Riccardo; Bootwalla, Moiz S; Bosenberg, Marcus; Bowen, Jay; Bowlby, Reanne; Bristow, Christopher A; Brockway-Lunardi, Laura; Brooks, Denise; Brzezinski, Jakub; Bshara, Wiam; Buda, Elizabeth; Burns, William R; Butterfield, Yaron SN; Button, Michael; Calderone, Tiffany; Cappellini, Giancarlo Antonini; Carter, Candace; Carter, Scott L; Cherney, Lynn; Cherniack, Andrew D; Chevalier, Aaron; Chin, Lynda; Cho, Juok; Cho, Raymond J; Choi, Yoon-La; Chu, Andy; Chudamani, Sudha; Cibulskis, Kristian; Ciriello, Giovanni; Clarke, Amanda; Coons, Stephen; Cope, Leslie; Crain, Daniel; Curley, Erin; Danilova, Ludmila; D’Atri, Stefania; Davidsen, Tanja; Davies, Michael A; Delman, Keith A; Demchok, John A; Deng, Qixia A; Deribe, Yonathan Lissanu; Dhalla, Noreen; Dhir, Rajiv; DiCara, Daniel; Dinikin, Michael; Dubina, Michael; Ebrom, J Stephen; Egea, Sophie; Eley, Greg; Engel, Jay; Eschbacher, Jennifer M; Fedosenko, Konstantin V; Felau, Ina; Fennell, Timothy; Ferguson, Martin L; Fisher, Sheila; Flaherty, Keith T; Frazer, Scott; Frick, Jessica; Fulidou, Victoria; Gabriel, Stacey B; Gao, Jianjiong; Gardner, Johanna; Garraway, Levi A; Gastier-Foster, Julie M; Gaudioso, Carmelo; Gehlenborg, Nils; Genovese, Giannicola; Gerken, Mark; Gershenwald, Jeffrey E
Source
Cell. 161(7)
Subject
Language
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.