Vulnerabilities of Mutant SWI/SNF Complexes in Cancer

Cancer genome sequencing efforts have revealed the novel theme that chromatin modifiers are frequently mutated across a wide spectrum of cancers. Mutations in genes encoding subunits of SWI/SNF (BAF) chromatin remodeling complexes are particularly prevalent, occurring in 20% of all human cancers. As...

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Bibliographic Details
Published in:Cancer cell 2014-09, Vol.26 (3), p.309-317
Main Authors: Helming, Katherine C., Wang, Xiaofeng, Roberts, Charles W.M.
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Genetic Predisposition to Disease
Humans
Molecular Targeted Therapy
Multiprotein Complexes - genetics
Mutation
Neoplasms - drug therapy
Neoplasms - genetics
Protein Subunits - genetics
Transcription Factors - genetics
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Summary:Cancer genome sequencing efforts have revealed the novel theme that chromatin modifiers are frequently mutated across a wide spectrum of cancers. Mutations in genes encoding subunits of SWI/SNF (BAF) chromatin remodeling complexes are particularly prevalent, occurring in 20% of all human cancers. As these are typically loss-of-function mutations and not directly therapeutically targetable, central goals have been to elucidate mechanism and identify vulnerabilities created by these mutations. Here, we discuss emerging data that these mutations lead to the formation of aberrant residual SWI/SNF complexes that constitute a specific vulnerability and discuss the potential for exploiting these dependencies in SWI/SNF mutant cancers.
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2014.07.018