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Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas
Cell. 2017 Nov;171(4) :950-965 e28
PMID: 29100075    PMCID: PMC5693358    URL: https://www.ncbi.nlm.nih.gov/pubmed/29100075
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Abstract
Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types.
Notes
Lazar, Alexander J. McLellan, Michael D. Bailey, Matthew H. Miller, Christopher A. Appelbaum, Elizabeth L. Cordes, Matthew G. Fronick, Catrina C. Fulton, Lucinda A. Fulton, Robert S. Mardis, Elaine R. Schmidt, Heather K. Wong, Winghing Wilson, Richard K. Yellapantula, Venkata Radenbaugh, Amie J. Hoadley, Katherine A. Hayes, D. Neil Parker, Joel S. Wilkerson, Matthew D. Auman, J. Todd Balu, Saianand Bodenheimer, Tom Hoyle, Alan P. Jefferys, Stuart R. Jones, Corbin D. Lehmann, Kjong-Van Meng, Shaowu Mieczkowski, Piotr A. Mose, Lisle E. Perou, Charles M. Roach, Jeffrey Senbabaoglu, Yasin Shi, Yan Simons, Janae V. Skelly, Tara Soloway, Matthew G. Tan, Donghui Veluvolu, Umadevi Davis, Ian J. Hepperla, Austin J. Brohl, Andrew S. Kasaian, Katayoon Mungall, Karen Sadeghi, Sara Barthel, Floris P. Verhaak, Roel Hu, Xin Chibon, Frederic Cherniack, Andrew D. Shih, Juliann Beroukhim, Rameen Meyerson, Matthew Cibulskis, Carrie Gabriel, Stacey B. Saksena, Gordon Schumacher, Steven E. Bailey, Matthew H. Gao, Qingsong Wong, Winghing Wyczalkowski, Matthew Bowlby, Reanne Robertson, A. Gordon Ally, Adrian Balasundaram, Miruna Brooks, Denise Carlsen, Rebecca Chuah, Eric Dhalla, Noreen Holt, Robert A. Jones, Steven J. M. Lee, Darlene Li, Irene Ma, Yussanne Marra, Marco A. Mayo, Michael Moore, Richard A. Mungall, Andrew J. Parker, Joel S. Schein, Jacqueline E. Sipahimalani, Payal Tam, Angela Thiessen, Nina Wong, Tina Danilova, Ludmila Cope, Leslie Baylin, Stephen B. Bootwalla, Moiz S. Lai, Phillip H. Laird, Peter W. Maglinte, Dennis T. Van Den Berg, David J. Weisenberger, Daniel J. Wrangle, John Drill, Esther Shen, Ronglai Iype, Lisa Reynolds, Sheila M. Shmulevich, Ilya Yau, Christina Armenia, Joshua Liu, Eric Minwei Benz, Christopher Pastore, Alessandro Sanchez-Vega, Francisco Schultz, Nikolaus Akbani, Rehan Hegde, Apurva M. Liu, Wenbin Lu, Yiling Mills, Gordon B. Weinstein, John N. Roszik, Jason Anur, Pavana Spellman, Paul Abeshouse, Adam Chen, Hsiao-Wei Gao, Jianjiong Heins, Zachary Kundra, Ritika Larsson, Erik Ochoa, Angelica Sanchez-Vega, Francisco Sander, Chris Schultz, Nikolaus Socci, Nicholas Zhang, Hongxin Noble, Michael S. Heiman, David I. Kim, Jaegil Chin, Lynda Getz, Gad Cho, Juok Defreitas, Timothy Frazer, Scott Gehlenborg, Nils Lawrence, Michael S. Lin, Pei Meier, Sam Voet, Doug Zhang, Hailei Byers, Lauren Diao, Lixia Gay, Carl M. Wang, Jing Newton, Yulia Cooper, Lee A. D. Gutman, David A. Lazar, Alexander J. Lee, Sanghoon Nalisnik, Michael Bowen, Jay Gastier-Foster, Julie M. Gerken, Mark Helsel, Carmen Hobensack, Shital Leraas, Kristen M. Lichtenberg, Tara M. Ramirez, Nilsa C. Wise, Lisa Zmuda, Erik Anderson, Matthew L. Castro, Patricia Ittmann, Michael Gordienko, Elena Paklina, Oxana Setdikova, Galiya Raut, Chandrajit P. Karlan, Beth Y. Lester, Jenny Belyaev, Dmitry Fulidou, Victoria Potapova, Olga Voronina, Olga Demetri, George D. Ramalingam, Suresh S. Behera, Madhusmita Delman, Keith Owonikoko, Taofeek K. Sica, Gabriel L. Boyd, Jeff Magliocco, Anthony Salner, Andrew Bennett, Joesph Iacocca, Mary Swanson, Patricia Dottino, Peter Kalir, Tamara Pereira, Elena Akeredolu, Teniola Crain, Daniel Curley, Erin Gardner, Johanna Mallery, David Morris, Scott Paulauskis, Joseph Penny, Robert Shelton, Candace Shelton, Troy Thompson, Eric Hoon, Dave B. Parfitt, Jeremy Birrer, Michael Karseladze, Apollon Mariamidze, Armaz Dao, Fanny Levine, Douglas A. Olvera, Narciso Maki, Robert G. Bartlett, John Eschbacher, Jennifer Dubina, Michael Mozgovoy, Evgeny Fedosenko, Konstantin Manikhas, Georgy Sekhon, Harman Ramirez, Nilsa Lazar, Alexander J. Ingram, Davis R. Torres, Keila E. DiSaia, Phil Godwin, Andrew K. Godwin, Eryn M. Kuo, Hanluen Madan, Rashna Reilly, Colleen Adebamowo, Clement Adebamowo, Sally N. Bocklage, Therese Higgins, Kelly Martinez, Cathleen Auman, J. Todd Boice, Lori Grilley-Olson, Juneko E. Huang, Mei Perou, Amy H. Thorne, Leigh B. Rathmell, W. Kimryn Gutmann, David H. Singer, Samuel Chudamani, Sudha Liu, Jia Lolla, Laxmi Naresh, Rashi Pihl, Todd Sun, Qiang Wan, Yunhu Wu, Ye Felau, Ina Zenklusen, Jean C. Demchok, John A. Ferguson, Martin L. Hutter, Carolyn M. Sofia, Heidi J. Tarnuzzer, Roy Wang, Zhining Yang, Liming Zhang, Jiashan (Julia) Demicco, Elizabeth G. Doyle, Leona A. Hornick, Jason L. Lazar, Alexander J. Rubin, Brian P. de Rijn, Matt van Demetri, George D. Baker, Laurence Grilley-Olson, Juneko E. Iype, Lisa Lazar, Alexander J. Lichtenberg, Tara M. Raut, Chandrajit P. Riedel, Richard F. Demicco, Elizabeth G. Ding, Li Ladanyi, Marc Lazar, Alexander J. Novak, Janet E. Sanchez-Vega, Francisco Singer, Samuel Van Tine, Brian A. Byers, Lauren Cope, Leslie Cherniack, Andrew D. Cooper, Lee A. D. Davis, Ian J. Davis, Lara E. Demetri, George D. Doyle, Leona A. Drill, Esther Godwin, Andrew K. Grilley-Olsen, Juneko E. Gutmann, David H. Hayes, D. Neil Hepperla, Austin J. Hoadley, Katherine A. Hoon, Dave B. Hornick, Jason L. Iype, Lisa Kim, Jaegil Maki, Robert G. Pollock, Raphael E. Raut, Chandrajit P. Riedel, Richard F. Robertson, A. Gordon Rubin, Brian P. Shih, Juliann Weinstein, John N. Wong, Winghing Akbani, Rehan Anderson, Matthew L. Anur, Pavana Bailey, Matthew H. Benz, Christopher Bowen, Jay Bowlby, Reanne Brohl, Andrew S. Cherniack, Andrew D. Cooper, Lee A. D. Cope, Leslie Danilova, Ludmila Davis, Lara E. Demetri, George D. Gay, Carl M. Godwin, Andrew K. Grilley-Olson, Juneko E. Gutman, David A. Hegde, Apurva M. Jones, Kevin B. Kasaian, Katayoon Ladanyi, Marc Lazar, Alexander J. Lee, Sanghoon Leraas, Kristen M. Lichtenberg, Tara M. Martignetti, John A. McLellan, Michael D. Miller, Christopher A. Mungall, Karen Nalisnik, Michael Noble, Michael S. Raut, Chandrajit P. Riedel, Richard F. Robertson, A. Gordon Roszik, Jason Sadeghi, Sara Sanchez-Vega, Francisco Shen, Ronglai Shih, Juliann Tong, Pan Torres, Keila E. Yau, Christina Zenklusen, Jean C. Roszik, Jason/0000-0002-4561-6170 1097-4172