Genomic Classification of Cutaneous Melanoma

The Cancer Genome Atlas Network, 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 Belyaev, Christopher 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, Lynda Chin, Juok Cho, Raymond J. Cho, Yoon-La Choi, Andy Chu, Sudha Chudamani, Kristian Cibulskis, Giovanni Ciriello, Amanda Clarke, Stephen Coons, Leslie Cope, Daniel Crain, Erin Curley, Ludmila Danilova, Stefania D’Atri, Tanja Davidsen, Michael A. Davies, Keith A. Delman, John A. Demchok, Qixia A. Deng, Yonathan Lissanu Deribe, Noreen Dhalla, Rajiv Dhir, Daniel DiCara, Michael Dinikin, Michael Dubina, J. Stephen Ebrom, Sophie Egea, Greg Eley, Jay Engel, Jennifer M. Eschbacher, Konstantin V. Fedosenko, Ina Felau, Timothy Fennell, Martin L. Ferguson, Sheila Fisher, Keith T. Flaherty, Scott Frazer, Jessica Frick, Victoria Fulidou, Stacey B. Gabriel, Jianjiong Gao, Johanna Gardner, Levi A. Garraway, Julie M. Gastier-Foster, Carmelo Gaudioso, Nils Gehlenborg, Giannicola Genovese, Mark Gerken, Jeffrey E. Gershenwald, Gad Getz, Carmen Gomez-Fernandez, Thomas Gribbin, Jonna Grimsby, Benjamin Gross, Ranabir Guin, Tony Gutschner, Angela Hadjipanayis, Ruth Halaban, Benjamin Hanf, David Haussler, Lauren E. Haydu, D. Neil Hayes, Nicholas K. Hayward, David I. Heiman, Lynn Herbert, James G. Herman, Peter Hersey, Katherine A. Hoadley, Eran Hodis, Robert A. Holt, Dave SB. Hoon, Susan Hoppough, Alan P. Hoyle, Franklin W. Huang, Mei Huang, Sharon Huang, Carolyn M. Hutter, Matthew Ibbs, Lisa Iype, Anders Jacobsen, Valerie Jakrot, Alyssa Janning, William R. Jeck, Stuart R. Jefferys, Mark A. Jensen, Corbin D. Jones, Steven J.M. Jones, Zhenlin Ju, Hojabr Kakavand, Hyojin Kang, Richard F. Kefford, Fadlo R. Khuri, Jaegil Kim, John M. Kirkwood, Joachim Klode, Anil Korkut, Konstanty Korski, Michael Krauthammer, Raju Kucherlapati, Lawrence N. Kwong, Witold Kycler, Marc Ladanyi, Phillip H. Lai, Peter W. Laird, Eric Lander, Michael S. Lawrence, Alexander J. Lazar, Radoslaw Łaźniak, Darlene Lee, Jeffrey E. Lee, Junehawk Lee, Kenneth Lee, Semin Lee, William Lee, Ewa Leporowska, Kristen M. Leraas, Haiyan I. Li, Tara M. Lichtenberg, Lee Lichtenstein, Pei Lin, Shiyun Ling, Jia Liu, Ouida Liu, Wenbin Liu, Georgina V. Long, Yiling Lu, Ma, Yussanne Ma, Andrzej Mackiewicz, Harshad S. Mahadeshwar, Jared Malke, David Mallery, Georgy M. Manikhas, Graham J. Mann, Marco A. Marra, Brenna Matejka, Michael Mayo, Sousan Mehrabi, Shaowu Meng, Matthew Meyerson, Piotr A. Mieczkowski, John P. Miller, Martin L. Miller, Gordon B. Mills, Fedor Moiseenko, Richard A. Moore, Scott Morris, Carl Morrison, Donald Morton, Stergios Moschos, Lisle E. Mose, Florian L. Muller, Andrew J. Mungall, Dawid Murawa, Pawel Murawa, Bradley A. Murray, Luigi Nezi, Sam Ng, Dana Nicholson, Michael S. Noble, Adeboye Osunkoya, Taofeek K. Owonikoko, Bradley A. Ozenberger, Elena Pagani, Oxana V. Paklina, Angeliki Pantazi, Michael Parfenov, Jeremy Parfitt, Peter J. Park, Woong-Yang Park, Joel S. Parker, Francesca Passarelli, Robert Penny, Charles M. Perou, Todd D. Pihl, Olga Potapova, Victor G. Prieto, Alexei Protopopov, Michael J. Quinn, Amie Radenbaugh, Kunal Rai, Suresh S. Ramalingam, Ayush T. Raman, Nilsa C. Ramirez, Ricardo Ramirez, Uma Rao, W. Kimryn Rathmell, Xiaojia Ren, Sheila M. Reynolds, Jeffrey Roach, A. Gordon Robertson, Merrick I. Ross, Jason Roszik, Giandomenico Russo, Gordon Saksena, Charles Saller, Yardena Samuels, Chris Sander, Cindy Sander, George Sandusky, Netty Santoso, Melissa Saul, Robyn PM. Saw, Dirk Schadendorf, Jacqueline E. Schein, Nikolaus Schultz, Steven E. Schumacher, Charles Schwallier, Richard A. Scolyer, Jonathan Seidman, Pedamallu Chandra Sekhar, Harmanjatinder S. Sekhon, Yasin Senbabaoglu, Sahil Seth, Kerwin F. Shannon, Samantha Sharpe, Norman E. Sharpless, Kenna R. Mills Shaw, Candace Shelton, Troy Shelton, Ronglai Shen, Margi Sheth, Yan Shi, Carolyn J. Shiau, Ilya Shmulevich, Gabriel L. Sica, Janae V. Simons, Rileen Sinha, Payal Sipahimalani, Heidi J. Sofia, Matthew G. Soloway, Xingzhi Song, Carrie Sougnez, Andrew J. Spillane, Arkadiusz Spychała, Jonathan R. Stretch, Joshua Stuart, Wiktoria M. Suchorska, Antje Sucker, S. Onur Sumer, Yichao Sun, Maria Synott, Barbara Tabak, Teresa R. Tabler, Angela Tam, Donghui Tan, Jiabin Tang, Roy Tarnuzzer, Katherine Tarvin, Honorata Tatka, Barry S. Taylor, Marek Teresiak, Nina Thiessen, John F. Thompson, Leigh Thorne, Vesteinn Thorsson, Jeffrey M. Trent, Timothy J. Triche, Kenneth Y. Tsai, Peiling Tsou, David J. Van Den Berg, Eliezer M. Van Allen, Umadevi Veluvolu, Roeland G. Verhaak, Douglas Voet, Olga Voronina, Vonn Walter, Jessica S. Walton, Yunhu Wan, Yuling Wang, Zhining Wang, Scot Waring, Ian R. Watson, Nils Weinhold, John N. Weinstein, Daniel J. Weisenberger, Peter White, Matthew D. Wilkerson, James S. Wilmott, Lisa Wise, Maciej Wiznerowicz, Scott E. Woodman, Chang-Jiun Wu, Chia-Chin Wu, Junyuan Wu, Ye Wu, Ruibin Xi, Andrew Wei Xu, Da Yang, Liming Yang, Lixing Yang, Travis I. Zack, Jean C. Zenklusen, Hailei Zhang, Jianhua Zhang, Wei Zhang, Xiaobei Zhao, Jingchun Zhu, Kelsey Zhu, Lisa Zimmer, Erik Zmuda, Lihua Zou

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.