| Title: |
Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas |
| Authors: |
Lazar, AJ; McLellan, MD; Bailey, MH; Miller, CA; Appelbaum, EL; Cordes, MG; Fronick, CC; Fulton, LA; Fulton, RS; Mardis, ER; Schmidt, HK; Wong, W; Wilson, RK; Yellapantula, V; Radenbaugh, AJ; Hoadley, KA; Hayes, DN; Parker, JS; Wilkerson, MD; Auman, JT; Balu, S; Bodenheimer, T; Hoyle, AP; Jefferys, SR; Jones, CD; Lehmann, K-V; Meng, S; Mieczkowski, PA; Mose, LE; Perou, CM; Roach, J; Senbabaoglu, Y; Shi, Y; Simons, JV; Skelly, T; Soloway, MG; Tan, D; Veluvolu, U; Davis, IJ; Hepperla, AJ; Brohl, AS; Kasaian, K; Mungall, K; Sadeghi, S; Barthel, FP; Verhaak, R; Hu, X; Chibon, F; Cherniack, AD; Shih, J; Beroukhim, R; Meyerson, M; Cibulskis, C; Gabriel, SB; Saksena, G; Schumacher, SE; Gao, Q; Wyczalkowski, M; Bowlby, R; Robertson, AG; Ally, A; Balasundaram, M; Brooks, D; Carlsen, R; Chuah, E; Dhalla, N; Holt, RA; Jones, SJM; Lee, D; Li, I; Ma, Y; Marra, MA; Mayo, M; Moore, RA; Mungall, AJ; Schein, JE; Sipahimalani, P; Tam, A; Thiessen, N; Wong, T; Danilova, L; Cope, L; Baylin, SB; Bootwalla, MS; Lai, PH; Laird, PW; Maglinte, DT; Van Den Berg, DJ; Weisenberger, DJ; Wrangle, J; Drill, E; Shen, R; Iype, L; Reynolds, SM; Shmulevich, I; Yau, C; Armenia, J; Liu, EM; Benz, C; Pastore, A; Sanchez-Vega, F; Schultz, N; Akbani, R; Hegde, AM; Liu, W; Lu, Y; Mills, GB; Weinstein, JN; Roszik, J; Anur, P; Spellman, P; Abeshouse, A; Chen, H-W; Gao, J; Heins, Z; Kundra, R; Larsson, E; Ochoa, A; Sander, C; Socci, N; Zhang, H; Noble, MS; Heiman, DI; Kim, J; Chin, L; Getz, G; Cho, J; Defreitas, T; Frazer, S; Gehlenborg, N; Lawrence, MS; Lin, P; Meier, S; Voet, D; Byers, L; Diao, L; Gay, CM; Wang, J; Newton, Y; Cooper, LAD; Gutman, DA; Lee, S; Nalisnik, M; Bowen, J; Gastier-Foster, JM; Gerken, M; Helsel, C; Hobensack, S; Leraas, KM; Lichtenberg, TM; Ramirez, NC; Wise, L; Zmuda, E; Anderson, ML; Castro, P; Ittmann, M; Gordienko, E; Paklina, O; Setdikova, G; Raut, CP; Karlan, BY; Lester, J; Belyaev, D; Fulidou, V; Potapova, O; Voronina, O; Demetri, GD; Ramalingam, SS; Behera, M; Delman, K; Owonikoko, TK; Sica, GL; Boyd, J; Magliocco, A; Salner, A; Bennett, J; Iacocca, M; Swanson, P; Dottino, P; Kalir, T; Pereira, E; Akeredolu, T; Crain, D; Curley, E; Gardner, J; Mallery, D; Morris, S; Paulauskis, J; Penny, R; Shelton, C; Shelton, T; Thompson, E; Hoon, DB; Parfitt, J; Birrer, M; Karseladze, A; Mariamidze, A; Dao, F; Levine, DA; Olvera, N; Maki, RG; Bartlett, J; Eschbacher, J; Dubina, M; Mozgovoy, E; Fedosenko, K; Manikhas, G; Sekhon, H; Ramirez, N; Ingram, DR; Torres, KE; DiSaia, P; Godwin, AK; Godwin, EM; Kuo, H; Madan, R; Reilly, C; Adebamowo, C; Adebamowo, SN; Bocklage, T; Higgins, K; Martinez, C; Boice, L; Grilley-Olson, JE; Huang, M; Perou, AH; Thorne, LB; Rathmell, WK; Gutmann, DH; Singer, S; Chudamani, S; Liu, J; Lolla, L; Naresh, R; Pihl, T; Sun, Q; Wan, Y; Wu, Y; Felau, I; Zenklusen, JC; Demchok, JA; Ferguson, ML; Hutter, CM; Sofia, HJ; Tarnuzzer, R; Wang, Z; Yang, L; Zhang, JJ; Demicco, EG; Doyle, LA; Hornick, JL; Rubin, BP; de Rijn, MV; Baker, L; Riedel, RF; Ding, L; Ladanyi, M; Novak, JE; Van Tine, BA; Davis, LE; Grilley-Olsen, JE; Pollock, RE; Jones, KB; Martignetti, JA; Tong, P |
| Source: |
Cell , 171 (4) 950-965.e28. (2017) |
| Publisher Information: |
CELL PRESS |
| Publication Year: |
2017 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Science & Technology; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; Cell Biology; SINGLE NUCLEOTIDE POLYMORPHISMS; SMOOTH-MUSCLE DIFFERENTIATION; SOMATIC POINT MUTATIONS; COPY NUMBER ALTERATION; SEQUENCING DATA; HUMAN CANCER; GENE-EXPRESSION; DISCOVERY; CELLS; VALIDATION |
| Description: |
Summary 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10038678/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10038678/1/1-s2.0-S0092867417312035-main.pdf; https://discovery.ucl.ac.uk/id/eprint/10038678/ |
| Rights: |
open |
| Accession Number: |
edsbas.99DE87D3 |
| Database: |
BASE |