表观遗传学
SMARCA4型
染色质
祖细胞
祖细胞
癌症研究
癌变
染色质重塑
组蛋白
生物
细胞生物学
医学
遗传学
干细胞
癌症
DNA
基因
作者
Mary Clare Beytagh,William A. Weiss
出处
期刊:Cancer Discovery
[American Association for Cancer Research]
日期:2022-12-02
卷期号:12 (12): 2730-2732
标识
DOI:10.1158/2159-8290.cd-22-1030
摘要
Epigenetic reprogramming drives tumorigenesis in pediatric H3K27M diffuse midline glioma (DMG) by altering the canonical functions of chromatin remodeling complexes. These 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. See related article by Panditharatna et al., p. 2880 (5) See related article by Mo et al., p. 2906 (4) .
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