Synapse - Comprehensive and integrated genomic characterization of adult soft tissue sarcomas

Comprehensive and integrated genomic characterization of adult soft tissue sarcomas Journal Article

Author:	The Cancer Genome Atlas Research Network
Contributors:	Drill, E.; Shen, R.; Armenia, J.; Sanchez-Vega, F.; Schultz, N.; Abeshouse, A.; Chen, H. W.; Gao, J.; Heins, Z.; Kundra, R.; Larsson, E.; Ochoa, A.; Sander, C.; Socci, N.; Zhang, H.; Lehmann, K. V.; Senbabaoglu, Y.; Liu, E. M.; Pastore, A.; Ladanyi, M.; Singer, S.; Novak, J. E.
Article Title:	Comprehensive and integrated genomic characterization of adult soft tissue sarcomas
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.
Keywords:	single nucleotide polymorphisms; validation; human cancer; gene-expression; somatic; cells; discovery; copy number alteration; point mutations; smooth-muscle differentiation; sequencing data
Journal Title:	Cell
Volume:	171
Issue:	4
ISSN:	0092-8674
Publisher:	Cell Press
Date Published:	2017-11-02
Start Page:	950
End Page:	965.e28
Language:	English
ACCESSION:	WOS:000414250900021
DOI:	10.1016/j.cell.2017.10.014
PROVIDER:	wos
PMCID:	PMC5693358
PUBMED:	29100075
Notes:	Article -- Source: Wos