Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas.

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


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.


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

Institute Authors