TY - JOUR
T1 - Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas
AU - The Cancer Genome Atlas Research Network
AU - Abeshouse, Adam
AU - Adebamowo, Clement
AU - Adebamowo, Sally N.
AU - Akbani, Rehan
AU - Akeredolu, Teniola
AU - Ally, Adrian
AU - Anderson, Matthew L.
AU - Anur, Pavana
AU - Appelbaum, Elizabeth L.
AU - Armenia, Joshua
AU - Auman, J. Todd
AU - Bailey, Matthew H.
AU - Baker, Laurence
AU - Balasundaram, Miruna
AU - Balu, Saianand
AU - Barthel, Floris P.
AU - Bartlett, John
AU - Baylin, Stephen B.
AU - Behera, Madhusmita
AU - Belyaev, Dmitry
AU - Bennett, Joesph
AU - Benz, Christopher
AU - Beroukhim, Rameen
AU - Birrer, Michael
AU - Bocklage, Thèrése
AU - Bodenheimer, Tom
AU - Boice, Lori
AU - Bootwalla, Moiz S.
AU - Bowen, Jay
AU - Bowlby, Reanne
AU - Boyd, Jeff
AU - Brohl, Andrew S.
AU - Brooks, Denise
AU - Byers, Lauren
AU - Carlsen, Rebecca
AU - Castro, Patricia
AU - Chen, Hsiao Wei
AU - Cherniack, Andrew D.
AU - Chibon, Fréderic
AU - Chin, Lynda
AU - Cho, Juok
AU - Chuah, Eric
AU - Chudamani, Sudha
AU - Ding, Li
AU - Fulton, Lucinda A.
AU - Fulton, Robert S.
AU - Gutmann, David H.
AU - Miller, Christopher A.
AU - Van Tine, Brian A.
AU - Wyczalkowski, Matthew
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/11/2
Y1 - 2017/11/2
N2 - 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. Genetic analysis of soft tissue sarcomas shows that they are characterized predominantly by copy-number changes and offers insights into the immune microenviroment to inform clinical trials of checkpoint inhibitors.
AB - 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. Genetic analysis of soft tissue sarcomas shows that they are characterized predominantly by copy-number changes and offers insights into the immune microenviroment to inform clinical trials of checkpoint inhibitors.
KW - DNA methylation
KW - The Cancer Genome Atlas
KW - dedifferentiated liposarcoma
KW - genomics
KW - immune infiltration
KW - leiomyosarcoma
KW - molecular subtype
KW - myxofibrosarcoma
KW - pleomorphism
KW - undifferentiated pleomorphic sarcoma
UR - http://www.scopus.com/inward/record.url?scp=85032697928&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2017.10.014
DO - 10.1016/j.cell.2017.10.014
M3 - Article
C2 - 29100075
AN - SCOPUS:85032697928
SN - 0092-8674
VL - 171
SP - 950-965.e28
JO - Cell
JF - Cell
IS - 4
ER -