Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics

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Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics

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Title: Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics
Author: Kadoch, Cigall; Crabtree, Gerald R.

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Citation: Kadoch, Cigall, and Gerald R. Crabtree. 2015. “Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics.” Science Advances 1 (5): e1500447. doi:10.1126/sciadv.1500447. http://dx.doi.org/10.1126/sciadv.1500447.
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Abstract: Over the past 4 years, nearly 100 exome sequencing studies have revealed the high frequency of mutations in the genes encoding the subunits of ATP-dependent chromatin remodelers in human cancer. Most of these mutations are within the genes encoding subunits of the BAF (Brg/Brahma-associated factors) or mSWI/SNF complex, which is one of two dozen predicted ATP-dependent chromatin remodeling complexes in mammals. Considering BAF complexes as a single entity, the 15 subunits encoded by 29 genes are mutated in >20% of human cancer, across a broad range of tumor types. These observations demonstrate that there is little redundancy in the oncogenic function of BAF complexes with the other remodeling complexes, underscoring their unique roles. Several important conclusions emerge from these genomic data: specific subunits appear to be mutated in specific cancers, highlighting tissue-specific protective roles; mutations can function as tumor suppressors or oncogenes; mutations can be homozygous or, more commonly, heterozygous, implying their dosage-sensitive roles in an unknown yet fundamental process used to suppress the genesis of cancer. These new human genetic findings paired with biochemical studies are challenging old ideas on how chromatin remodeling complexes function, generating new hypotheses with respect to their normal and oncogenic mechanisms and highlighting potential avenues for therapeutic intervention in human cancer.
Published Version: doi:10.1126/sciadv.1500447
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640607/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845143
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