Epigenetic mechanisms and therapeutic advances in diffuse midline glioma (Review)

Gliomas are the most common primary malignant tumors of the central nervous system in adults, with diffuse midline gliomas (DMG) being particularly aggressive and associated with inferior survival rate. Notwithstanding advances in molecular diagnostics and epigenetics, the specific pathological mechanisms of DMG remain to be fully elucidated. A series of studies have demonstrated that histone modifications, particularly the histone H3 lysine 27 (H3K27)M mutation, play a pivotal role in the development and progression of DMG. The mutation disrupts histone methylation and acetylation to induce widespread gene expression abnormalities, tumor aggressiveness and treatment resistance. Conventional treatments such as surgery, local radiotherapy and chemotherapy offer limited efficacy. However, emerging precision therapies targeting histone mutations, epigenetic modifications and innovative immunotherapies show promise in improving outcomes. The present study provided a comprehensive overview of the molecular mechanisms, epigenetic characteristics and the latest therapeutic advances in DMG. By investigating the H3K27M mutation and its associated epigenetic mechanisms, the present review aimed to establish theoretical frameworks and research avenues for developing precise therapeutic strategies for DMG, thus contributing to advancing the field of personalized medicine.