Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas.
- Author(s): Cancer Genome Atlas Research Network. Electronic address: firstname.lastname@example.org
- Cancer Genome Atlas Research Network
- et al.
Published Web Locationhttps://ac.els-cdn.com/S0092867417312035/1-s2.0-S0092867417312035-main.pdf?_tid=dbdc5b2c-ce2b-11e7-aba7-00000aacb360&acdnat=1511207522_2c3844f2d0cede590641e6002de15911
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.