儿童高级别胶质瘤是脑肿瘤的一个毁灭性亚型，其特点是具有侵袭性的病理生理学和有限的治疗选择。其中，H3 K27 改变的脑干弥漫性中线胶质瘤 (DMG) 由于其独特的分子特征和糟糕的预后而脱颖而出。分子分析技术的最新进展揭示了 H3 K27 改变在 DMG 发病机制中的关键作用，特别是组蛋白 H3 尾部 27 位 (K27M) 的赖氨酸到蛋氨酸的突变。这些突变导致表观遗传失调，从而导致 DMG 肿瘤细胞中染色质结构和基因表达模式的改变，最终导致 DMG 的侵袭性表型。近年来，DMG 靶向治疗途径的探索势头强劲。包括表观遗传修饰剂、激酶抑制剂和免疫疗法在内的治疗方法正在积极研究中；这些方法旨在破坏异常的信号级联反应并克服 DMG 中的各种治疗耐药机制。血脑屏障渗透和 DMG 肿瘤异质性等挑战需要创新方法来改善药物输送和个性化治疗策略。本综述旨在全面概述对 DMG 不断发展的理解，重点关注驱动肿瘤发生/肿瘤进展的复杂分子机制以及新兴靶向干预措施的现状。

Pediatric high-grade gliomas are a devastating subset of brain tumors, characterized by their aggressive pathophysiology and limited treatment options. Among them, H3 K27-altered diffuse midline gliomas (DMG) of the brainstem stand out due to their distinct molecular features and dismal prognosis. Recent advances in molecular profiling techniques have unveiled the critical role of H3 K27 alterations, particularly a lysine-to-methionine mutation on position 27 (K27M) of the histone H3 tail, in the pathogenesis of DMG. These mutations result in epigenetic dysregulation, which leads to altered chromatin structure and gene expression patterns in DMG tumor cells, ultimately contributing to the aggressive phenotype of DMG. The exploration of targeted therapeutic avenues for DMG has gained momentum in recent years. Therapies, including epigenetic modifiers, kinase inhibitors, and immunotherapies, are under active investigation; these approaches aim to disrupt aberrant signaling cascades and overcome the various mechanisms of therapeutic resistance in DMG. Challenges, including blood-brain barrier penetration and DMG tumor heterogeneity, require innovative approaches to improve drug delivery and personalized treatment strategies. This review aims to provide a comprehensive overview of the evolving understanding of DMG, focusing on the intricate molecular mechanisms driving tumorigenesis/tumor progression and the current landscape of emerging targeted interventions.