학술논문
Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas
Document Type
article
Author
Network, The Cancer Genome Atlas Research; Abeshouse, Adam; Adebamowo, Clement; Adebamowo, Sally N; Akbani, Rehan; Akeredolu, Teniola; Ally, Adrian; Anderson, Matthew L; Anur, Pavana; Appelbaum, Elizabeth L; Armenia, Joshua; Auman, J Todd; Bailey, Matthew H; Baker, Laurence; Balasundaram, Miruna; Balu, Saianand; Barthel, Floris P; Bartlett, John; Baylin, Stephen B; Behera, Madhusmita; Belyaev, Dmitry; Bennett, Joesph; Benz, Christopher; Beroukhim, Rameen; Birrer, Michael; Bocklage, Thèrése; Bodenheimer, Tom; Boice, Lori; Bootwalla, Moiz S; Bowen, Jay; Bowlby, Reanne; Boyd, Jeff; Brohl, Andrew S; Brooks, Denise; Byers, Lauren; Carlsen, Rebecca; Castro, Patricia; Chen, Hsiao-Wei; Cherniack, Andrew D; Chibon, Fréderic; Chin, Lynda; Cho, Juok; Chuah, Eric; Chudamani, Sudha; Cibulskis, Carrie; Cooper, Lee AD; Cope, Leslie; Cordes, Matthew G; Crain, Daniel; Curley, Erin; Danilova, Ludmila; Dao, Fanny; Davis, Ian J; Davis, Lara E; Defreitas, Timothy; Delman, Keith; Demchok, John A; Demetri, George D; Demicco, Elizabeth G; Dhalla, Noreen; Diao, Lixia; Ding, Li; DiSaia, Phil; Dottino, Peter; Doyle, Leona A; Drill, Esther; Dubina, Michael; Eschbacher, Jennifer; Fedosenko, Konstantin; Felau, Ina; Ferguson, Martin L; Frazer, Scott; Fronick, Catrina C; Fulidou, Victoria; Fulton, Lucinda A; Fulton, Robert S; Gabriel, Stacey B; Gao, Jianjiong; Gao, Qingsong; Gardner, Johanna; Gastier-Foster, Julie M; Gay, Carl M; Gehlenborg, Nils; Gerken, Mark; Getz, Gad; Godwin, Andrew K; Godwin, Eryn M; Gordienko, Elena; Grilley-Olson, Juneko E; Gutman, David A; Gutmann, David H; Hayes, D Neil; Hegde, Apurva M; Heiman, David I; Heins, Zachary; Helsel, Carmen; Hepperla, Austin J; Higgins, Kelly; Hoadley, Katherine A; Hobensack, Shital
Source
Cell. 171(4)
Subject
Language
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.