brg1 [Neurosurgery Wiki]

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BRG1 (or SMARCA4) is the most frequently mutated [[chromatin remodeling]] [[ATPase]] in cancer. Mutations in this gene were first recognized in human cancer cell lines derived from the adrenal gland and lung.
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Studies (i) identified [[BRG1]] (encoded by SMARCA4), the catalytic subunit of the mammalian SWI/SNF (BAF) chromatin remodeling complex, as a novel dependency in pediatric H3K27M glioma; (ii) investigated the molecular mechanisms underlying the maintenance of the progenitor state; and (iii) demonstrated efficacy for BRG1 inhibitors. The authors identified the BRG1 ATPase as a dependency in pediatric H3K27M-mutant DMG. SOX10 recruits BRG1 to regulatory elements to drive progression. Pharmacologically targeting BRG1 reduced tumor volume and improved survival in vivo. Inhibiting BRG1 ATPase represents a potential therapeutic strategy for pediatric H3K27M DMG
((Beytagh MC, Weiss WA. Epigenetic Rewiring Underlies SMARCA4-Dependent Maintenance of Progenitor State in Pediatric H3K27M Diffuse Midline Glioma. Cancer Discov. 2022 Dec 2;12(12):2730-2732. doi: 10.1158/2159-8290.CD-22-1030. PMID: 36458436.))