Disruption of mammalian SWI/SNF and polycomb complexes in human sarcomas: mechanisms and therapeutic opportunities. Issue 5 (6th March 2018)

• Record Type: Journal Article
• Authors: McBride, Matthew J; Kadoch, Cigall
• Editors: Huntsman, David G; Ladanyi, Marc
• Is Part Of: Journal of pathology. Volume 244:Issue 5(2018)
• Page Start: 638
• Page End: 649
• Publication Date: 2018-03-06
• Subjects: soft‐tissue sarcoma -- epigenetic regulation -- chromatin remodeling -- mSWI/SNF complexes -- BAF complexes -- polycomb repressive complexes -- fusion oncoproteins, oncogenesis; Pathology -- Periodicals; 616.07
• DOI: 10.1002/path.5042
• Languages: English
• ISSNs: 0022-3417

Abstract

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.