Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Cancer Genome Atlas ResearchNetwork, (November 2017) Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas. Cell, 171 (4). 950-965.e28. ISSN 0092-8674

URL: https://www.ncbi.nlm.nih.gov/pubmed/29100075
DOI: 10.1016/j.cell.2017.10.014

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Adult Aged Aged, 80 and over Cluster Analysis DNA Copy Number Variations Epigenomics Genome, Human Genome-Wide Association Study Humans Middle Aged Mutation Sarcoma/diagnosis/*genetics/pathology Young Adult DNA methylation The Cancer Genome Atlas dedifferentiated liposarcoma genomics immune infiltration leiomyosarcoma molecular subtype myxofibrosarcoma pleomorphism undifferentiated pleomorphic sarcoma
Subjects: diseases & disorders > cancer > cancer types > sarcoma
CSHL Authors:
Communities: CSHL Cancer Center Program > Signal Transduction
CSHL labs > Maki lab
Depositing User: Matt Covey
Date: 2 November 2017
Date Deposited: 13 Jun 2018 19:38
Last Modified: 13 Jun 2018 19:38
PMCID: PMC5693358
Related URLs:
URI: http://repository.cshl.edu/id/eprint/36718

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