Molecular Pathways: SWI/SNF (BAF) Complexes Are Frequently Mutated in Cancer—Mechanisms and Potential Therapeutic Insights

SWI/SNF chromatin remodeling complexes are pleomorphic multisubunit cellular machines that utilize the energy of ATP hydrolysis to modulate chromatin structure. The complexes interact with transcription factors at promoters and enhancers to modulate gene expression and contribute to lineage specific...

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Bibliographic Details
Published in:Clinical cancer research 2014-01, Vol.20 (1), p.21-27
Main Authors: XIAOFENG WANG, HASWELL, Jeffrey R, ROBERTS, Charles W. M
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Chromosomal Proteins, Non-Histone - genetics
Chromosomal Proteins, Non-Histone - metabolism
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Humans
Medical sciences
Molecular Targeted Therapy
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Mutation
Neoplasms - drug therapy
Neoplasms - genetics
Pharmacology. Drug treatments
Protein Subunits - genetics
Protein Subunits - metabolism
Signal Transduction
Transcription Factors - genetics
Transcription Factors - metabolism
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
Tumors
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Summary:SWI/SNF chromatin remodeling complexes are pleomorphic multisubunit cellular machines that utilize the energy of ATP hydrolysis to modulate chromatin structure. The complexes interact with transcription factors at promoters and enhancers to modulate gene expression and contribute to lineage specification, differentiation, and development. Initial clues to a role in tumor suppression for SWI/SNF complexes came over a decade ago when the gene encoding the SMARCB1/SNF5 core subunit was found specifically inactivated in nearly all pediatric rhabdoid tumors. In the last three years, cancer-genome sequencing efforts have revealed an unexpectedly high mutation rate of SWI/SNF subunit genes, which are collectively mutated in 20% of all human cancers and approach the frequency of p53 mutations. Here, we provide a background on these newly recognized tumor suppressor complexes, discuss mechanisms implicated in the tumor suppressor activity, and highlight findings that may lead to potential therapeutic targets for SWI/SNF-mutant cancers.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.ccr-13-0280