Central nervous system (CNS) tumors represent a formidable clinical challenge due to their molecular complexity and varied prognostic outcomes. This review delves into the pivotal role of the epigenetic marker H3K27me3 in the development and treatment of CNS tumors. H3K27me3, specifically the trimethylation of lysine 27 on the histone H3 protein, plays a crucial role in regulating gene expression and maintaining chromatin architecture (e.g., in X-chromosome inactivation). Notably, a reduction in H3K27me3 levels, frequently tied to mutations in the H3 gene family such as H3F3A and HIST1H3B, is evident in diverse brain tumor variants, including the diffuse midline glioma characterized by the H3K27M mutation and certain pediatric high-grade gliomas. The loss of H3K27me3 has been linked to more aggressive behavior in meningiomas, with the trimethylation loss associated with significantly shorter recurrence-free survival (RFS) among grade 2 meningiomas, albeit not within grade 1 tumors. Pediatric posterior fossa ependymomas characterized by a lowered H3K27me3 and DNA hypomethylation exhibit poor prognosis, underscoring the prognostic significance of these epigenetic alterations in CNS tumors. Comprehending the role of H3K27me3 in CNS tumors is vital for advancing diagnostic tools and therapeutic interventions, with the goal of enhancing patient outcomes and quality of life. This review underscores the importance of ongoing investigations into H3K27me to refine and optimize management strategies for CNS tumors, paving the way for improved personalized medicine practices in oncology.
中枢神经系统肿瘤因其分子复杂性及预后差异构成严峻的临床挑战。本综述深入探讨表观遗传标记物H3K27me3在中枢神经系统肿瘤发生发展及治疗中的关键作用。H3K27me3作为组蛋白H3第27位赖氨酸的三甲基化修饰，在基因表达调控和染色质结构维持（如X染色体失活）中发挥重要作用。值得注意的是，H3K27me3水平降低现象广泛存在于多种脑肿瘤亚型中，常与H3F3A、HIST1H3B等组蛋白基因突变相关，尤以伴H3K27M突变的弥漫性中线胶质瘤及部分儿童高级别胶质瘤为典型代表。在脑膜瘤中，H3K27me3缺失与肿瘤侵袭性增强相关，其中2级脑膜瘤患者的三甲基化缺失与无复发生存期显著缩短密切相关，而1级肿瘤中未见此关联。以H3K27me3降低和DNA低甲基化为特征的儿童后颅窝室管膜瘤预后不良，凸显了这些表观遗传改变在中枢神经系统肿瘤中的预后价值。深入理解H3K27me3在中枢神经系统肿瘤中的作用机制，对推进诊断工具研发和治疗策略创新至关重要，有助于改善患者预后及生活质量。本综述强调持续开展H3K27me相关研究对优化中枢神经系统肿瘤管理策略的重要意义，为推进肿瘤个体化精准医疗实践开辟新路径。
H3K27me3 Loss in Central Nervous System Tumors: Diagnostic, Prognostic, and Therapeutic Implications
肿瘤(癌症)患者之家