Disruption of mammalian SWI/SNF and polycomb complexes in human sarcomas: mechanisms and therapeutic opportunities.

J Pathol
Authors
Keywords
Abstract

Soft-tissue sarcomas are increasingly characterized and subclassified by genetic abnormalities that represent underlying drivers of their pathology. Hallmark tumor suppressor gene mutations and pathognomonic gene fusions collectively account for approximately one-third of all sarcomas. These genetic abnormalities most often result in global transcriptional misregulation via disruption of protein regulatory complexes which govern chromatin architecture. Specifically, alterations to mammalian SWI/SNF (mSWI/SNF or BAF) ATP-dependent chromatin remodeling complexes and polycomb repressive complexes cause disease-specific changes in chromatin architecture and gene expression across a number of sarcoma subtypes. Understanding the functions of chromatin regulatory complexes and the mechanisms underpinning their roles in oncogenesis will be required for the design and development of new therapeutic strategies in sarcomas. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Year of Publication
2018
Journal
J Pathol
Volume
244
Issue
5
Pages
638-649
Date Published
2018 04
ISSN
1096-9896
DOI
10.1002/path.5042
PubMed ID
29359803
PubMed Central ID
PMC6755911
Links
Grant list
DP2 CA195762 / CA / NCI NIH HHS / United States
R01 CA237241 / CA / NCI NIH HHS / United States
T32 GM095450 / GM / NIGMS NIH HHS / United States