Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Authors: Daniel J. Weisenberger, Candace Shelton, Matthew Meyerson, Carrie Cibulskis, Jia Liu, Joshua Armenia, Christina Yau, Dennis T. Maglinte, Rehan Akbani, David Van Den Berg, Nikolaus Schultz, Matthew L. Anderson, Armaz Mariamidze, Beth Y. Karlan, Amie Radenbaugh, Eric Thompson, Matthew D. Wilkerson, Qiang Sun, Francisco Sánchez-Vega, Yulia Newton, Teniola Akeredolu, Jean C. Zenklusen, Davis R. Ingram, Elizabeth L. Appelbaum, Madhusmita Behera, Chandrajit P. Raut, Ye Wu, Shaowu Meng, Phil DiSaia, Richard F. Riedel, Tara Skelly, Tara M. Lichtenberg, Clement Adebamowo, Heidi J. Sofia, Carmen Helsel, Matt van de Rijn, Erin Curley, Andrew D. Cherniack, Rashi Naresh, Fanny Dao, Peter W. Laird, Michael Ittmann, Andrew K. Godwin, Darlene Lee, Heather K. Schmidt, Chris Sander, Yiling Lu, Jaegil Kim, Matthew A. Wyczalkowski, Matthew G. Cordes, Lisle E. Mose, Martin L. Ferguson, Nils Gehlenborg, Roel G.W. Verhaak, Mei Huang, Pan Tong, Joel S. Parker, Piotr A. Mieczkowski, Gabriel Sica, Yan Shi, Miruna Balasundaram, Reanne Bowlby, Sudha Chudamani, Bootwalla, Moiz S., Marco A. Marra, Janae V. Simons, Douglas A. Levine, Esther Drill, Rashna Madan, John Wrangle, Jeffrey Roach, А. И. Карселадзе, Jing Wang, J. Novak, Lynda Chin, Jeff Boyd, Konstantin Fedosenko, Keila E. Torres, Karen Mungall, W. Kimryn Rathmell, Michael D. McLellan, Payal Sipahimalani, Lixia Diao, Charles M. Perou, Georgy M. Manikhas, Carl M. Gay, Eric Minwei Liu, Rameen Beroukhim, Tom Bodenheimer, Winghing Wong, David I. Heiman, David Mallery, John Bartlett, Jenny Lester, David A. Gutman, Suresh S. Ramalingam, J. Todd Auman, Venkata Yellapantula, Jennifer Eschbacher, Julie M. Gastier-Foster, Angelica Ochoa, Paul T. Spellman, Denise Brooks, Anthony M. Magliocco, Erik Larsson, Wenbin Liu, Kevin B. Jones, Hailei Zhang, Jefferys, Stuart R., Wang, Zhining, Adrian Ally, Michael Mayo, Elaine R. Mardis, Richard K. Wilson, Adam Abeshouse, Patricia Swanson, Tamara Kalir, Juliann Shih, Li Ding, Michael J. Birrer, Alan P. Hoyle, Sally N. Adebamowo, Saianand Balu, Troy Shelton, Yunhu Wan, Raphael E. Pollock, Matthew G. Soloway, Meier, Sam, Dave S.�B. Hoon, Rebecca Carlsen, Roy Tarnuzzer, A. Gordon Robertson, Lucinda A. Fulton, Stacey Gabriel, Michael S. Lawrence, Timothy Defreitas, Ludmila Danilova, Castro, Patricia, Andrew Salner, Elizabeth G. Demicco, Gad Getz, Eric Chuah, Lori Boice, Jiashan Zhang, Katherine A. Hoadley, John N. Weinstein, Peter Dottino, Leona A. Doyle, Ina Felau, Steven J.M. Jones, Е. Н. Гордиенко, Andrew S. Brohl, Robert S. Fulton, Jianjiong Gao, Scott Frazer, Oxana Paklina, Amy H. Perou, Sanghoon Lee, Nilsa C. Ramirez, Leslie Cope, Lauren A. Byers, Sara Sadeghi, Ilya Shmulevich, Irene Li, Michael Dubina, Scott Morris, Nina Thiessen, D. K. Belyaev, Tina Wong, Doug Voet, Ritika Kundra, Richard A. Moore, Colleen Reilly, Jacqueline E. Schein, Carolyn M. Hutter, Ian J. Davis, Pavana Anur, Samuel Singer, Michael Nalisnik, Lara E. Davis, Ronglai Shen, Thèrése Bocklage, Apurva M. Hegde, Leigh B. Thorne, Jason Roszik, Angela Tam, Corbin D. Jones, Marc Ladanyi, Laurence H. Baker, Robert G. Maki, Jay Bowen, Kjong-Van Lehmann, Donghui Tan, Olga Potapova, Jeremy Parfitt, Elena Pereira, Michael S. Noble, Alessandro Pastore, Kristen M. Leraas, Alexander J. Lazar, Noreen Dhalla, Todd Pihl, Zachary Heins, C. Gaspar Martinez, Lisa Iype, Qingsong Gao, George D. Demetri, Laxmi Lolla, Gordon B. Mills, Hongxin Zhang, Gordon Saksena, John A. Demchok, Kelly J. Higgins, Lee Cooper, D. Neil Hayes, Olga L. Voronina, Yasin Şenbabaoğlu, Evgeny Mozgovoy, Floris P Barthel, Hsiao‐Wei Chen, Austin J. Hepperla, Erik Zmuda, Taofeek K. Owonikoko, Andrew J. Mungall, Lisa Wise, Steven E. Schumacher, Hanluen Kuo, David H. Gutmann, Shital Hobensack, Xin Hu, Frédéric Chibon, Matthew H. Bailey, Sheila M. Reynolds, Keith A. Delman, Juneko E. Grilley‐Olson, John A. Martignetti, Christopher A. Miller, Robert A. Holt, Phillip H. Lai, Robert Penny, Galiya Setdikova, Joseph Paulauskis, Stephen B. Baylin, Kasaian, Katayoon, Liming Yang, Brian A. Van Tine, Joesph Bennett, Victoria Fulidou, Eryn M. Godwin, Umadevi Veluvolu, Harman Sekhon, Mary Iacocca, Nicholas D. Socci, Brian P. Rubin, Yussanne Ma, Jason L. Hornick, Pei Lin, Catrina C. Fronick, Mark Gerken, Daniel Crain, Christopher C. Benz, Narciso Olvera, Juok Cho, Johanna Gardner - 2020 cited by 18

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 (, , ) 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.