Scientific Publications Database

Article Title: Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas
Authors: 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.
Journal: CELL Volume 171 Issue 4
Date of Publication:2017
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.