Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas.

Cancer Genome Atlas Research Network. Electronic address: elizabeth.demicco@sinaihealthsystem.ca, Cancer Genome Atlas Research Network
Cell. 2017 171 (4): 950-965.e28

PMID: 29100075 · PMCID: PMC5693358 · 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.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

MeSH Terms (14)

Adult Aged Aged, 80 and over Cluster Analysis DNA Copy Number Variations Epigenomics Genome, Human Genome-Wide Association Study Humans Middle Aged Mutation Sarcoma Sarcoma Young Adult

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