表观遗传重布线是儿童 H3K27M 弥漫性中线脑胶质瘤中 SMARCA4 依赖性祖细胞状态维持的基础。
Epigenetic Rewiring Underlies SMARCA4-Dependent Maintenance of Progenitor State in Pediatric H3K27M Diffuse Midline Glioma.
机构信息
Medical Scientist Training Program, Biomedical Sciences Training Program, University of California, San Francisco, San Francisco, California.
Depart-ments of Neuro-logy, Pediatrics, and Neurosurgery, University of California, San Francisco, San Francisco, California.
出版信息
Cancer Discov. 2022 Dec 2;12(12):2730-2732. doi: 10.1158/2159-8290.CD-22-1030.
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) .
表观遗传重编程通过改变染色质重塑复合物的典型功能，驱动儿科 H3K27M 弥漫性中线胶质瘤（DMG）的肿瘤发生。这些研究：（i）确定了 BRG1（由 SMARCA4 编码），即哺乳动物 SWI/SNF（BAF）染色质重塑复合物的催化亚基，是儿科 H3K27M 神经胶质瘤的新的依赖性因素；（ii）研究了维持祖细胞状态的分子机制；（iii）证明了 BRG1 抑制剂的功效。作者确定 BRG1 ATP 酶是儿科 H3K27M 突变型 DMG 的依赖性因素。SOX10 将 BRG1 募集到调节元件以驱动进展。药理学靶向 BRG1 减少了体内肿瘤体积并提高了生存率。抑制 BRG1 ATP 酶代表了治疗儿科 H3K27M DMG 的潜在治疗策略。见 Panditharatna 等人的相关文章，第 2880 页（5）见 Mo 等人的相关文章，第 2906 页（4）。
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