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Cell. 2017 Nov 2;171(4):950-965.e28. doi: 10.1016/j.cell.2017.10.014.

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas.

Collaborators (264)

Abeshouse A, Adebamowo C, Adebamowo SN, Akbani R, Akeredolu T, Ally A, Anderson ML, Anur P, Appelbaum EL, Armenia J, Auman JT, Bailey MH, Baker L, Balasundaram M, Balu S, Barthel FP, Bartlett J, Baylin SB, Behera M, Belyaev D, Bennett J, Benz C, Beroukhim R, Birrer M, Bocklage T, Bodenheimer T, Boice L, Bootwalla MS, Bowen J, Bowlby R, Boyd J, Brohl AS, Brooks D, Byers L, Carlsen R, Castro P, Chen HW, Cherniack AD, Chibon F, Chin L, Cho J, Chuah E, Chudamani S, Cibulskis C, Cooper LAD, Cope L, Cordes MG, Crain D, Curley E, Danilova L, Dao F, Davis IJ, Davis LE, Defreitas T, Delman K, Demchok JA, Demetri GD, Demicco EG, Dhalla N, Diao L, Ding L, DiSaia P, Dottino P, Doyle LA, Drill E, Dubina M, Eschbacher J, Fedosenko K, Felau I, Ferguson ML, Frazer S, Fronick CC, Fulidou V, Fulton LA, Fulton RS, Gabriel SB, Gao J, Gao Q, Gardner J, Gastier-Foster JM, Gay CM, Gehlenborg N, Gerken M, Getz G, Godwin AK, Godwin EM, Gordienko E, Grilley-Olson JE, Gutman DA, Gutmann DH, Hayes DN, Hegde AM, Heiman DI, Heins Z, Helsel C, Hepperla AJ, Higgins K, Hoadley KA, Hobensack S, Holt RA, Hoon DB, Hornick JL, Hoyle AP, Hu X, Huang M, Hutter CM, Iacocca M, Ingram DR, Ittmann M, Iype L, Jefferys SR, Jones KB, Jones CD, Jones SJM, Kalir T, Karlan BY, Karseladze A, Kasaian K, Kim J, Kundra R, Kuo H, Ladanyi M, Lai PH, Laird PW, Larsson E, Lawrence MS, Lazar AJ, Lee S, Lee D, Lehmann KV, Leraas KM, Lester J, Levine DA, Li I, Lichtenberg TM, Lin P, Liu J, Liu W, Liu EM, Lolla L, Lu Y, Ma Y, Madan R, Maglinte DT, Magliocco A, Maki RG, Mallery D, Manikhas G, Mardis ER, Mariamidze A, Marra MA, Martignetti JA, Martinez C, Mayo M, McLellan MD, Meier S, Meng S, Meyerson M, Mieczkowski PA, Miller CA, Mills GB, Moore RA, Morris S, Mose LE, Mozgovoy E, Mungall AJ, Mungall K, Nalisnik M, Naresh R, Newton Y, Noble MS, Novak JE, Ochoa A, Olvera N, Owonikoko TK, Paklina O, Parfitt J, Parker JS, Pastore A, Paulauskis J, Penny R, Pereira E, Perou CM, Perou AH, Pihl T, Pollock RE, Potapova O, Radenbaugh AJ, Ramalingam SS, Ramirez NC, Rathmell WK, Raut CP, Riedel RF, Reilly C, Reynolds SM, Roach J, Robertson AG, Roszik J, Rubin BP, Sadeghi S, Saksena G, Salner A, Sanchez-Vega F, Sander C, Schein JE, Schmidt HK, Schultz N, Schumacher SE, Sekhon H, Senbabaoglu Y, Setdikova G, Shelton C, Shelton T, Shen R, Shi Y, Shih J, Shmulevich I, Sica GL, Simons JV, Singer S, Sipahimalani P, Skelly T, Socci N, Sofia HJ, Soloway MG, Spellman P, Sun Q, Swanson P, Tam A, Tan D, Tarnuzzer R, Thiessen N, Thompson E, Thorne LB, Tong P, Torres KE, van de Rijn M, Van Den Berg DJ, Van Tine BA, Veluvolu U, Verhaak R, Voet D, Voronina O, Wan Y, Wang Z, Wang J, Weinstein JN, Weisenberger DJ, Wilkerson MD, Wilson RK, Wise L, Wong T, Wong W, Wrangle J, Wu Y, Wyczalkowski M, Yang L, Yau C, Yellapantula V, Zenklusen JC, Zhang JJ, Zhang H, Zhang H, Zmuda E.

Author information

1
Cancer Genome Atlas Program Office, National Cancer Institute at NIH, 31 Center Drive, Bldg. 31, Suite 3A20, Bethesda, MD 20892, USA.

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.

KEYWORDS:

DNA methylation; The Cancer Genome Atlas; dedifferentiated liposarcoma; genomics; immune infiltration; leiomyosarcoma; molecular subtype; myxofibrosarcoma; pleomorphism; undifferentiated pleomorphic sarcoma

PMID:
29100075
PMCID:
PMC5693358
DOI:
10.1016/j.cell.2017.10.014
[Indexed for MEDLINE]
Free PMC Article

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