Ependymomas (EPN) are tumors of the central nervous system (CNS) that can arise in the supratentorial brain (ST-EPN), hindbrain or posterior fossa (PF-EPN) or anywhere in the spinal cord (SP-EPN), both in children and adults. Molecular profiling studies have identified distinct groups and subtypes in each of these anatomical compartments. In this review, we give an overview on recent findings and new insights what is driving PFA ependymomas, which is the most common group. PFA ependymomas are characterized by a young median age at diagnosis, an overall balanced genome and a bad clinical outcome (56% 10-year overall survival). Sequencing studies revealed no fusion genes or other highly recurrently mutated genes, suggesting that the disease is epigenetically driven. Indeed, recent findings have shown that the characteristic global loss of the repressive histone 3 lysine 27 trimethylation (H3K27me3) mark in PFA ependymoma is caused by aberrant expression of the enhancer of zeste homolog inhibitory protein (EZHIP) or in rare cases by H3K27M mutations, which both inhibit EZH2 thereby preventing the polycomb repressive complex 2 (PRC2) from spreading H3K27me3. We present the current status of the ongoing work on EZHIP and its essential role in the epigenetic disturbance of PFA biology. Comparisons to the oncohistone H3K27M and its role in diffuse midline glioma (DMG) are drawn, highlighting similarities but also differences between the tumor entities and underlying mechanisms. A strong focus is to point out missing information and to present directions of further research that may result in new and improved therapies for PFA ependymoma patients.

室管膜瘤 (EPN) 是中枢神经系统 (CNS) 的肿瘤，可出现在幕上脑 (ST-EPN)、后脑或后颅窝 (PF-EPN) 或脊髓任何部位 (SP-EPN)，两者均位于儿童和成人。分子谱研究已经在这些解剖隔间中确定了不同的组和亚型。在这篇综述中，我们概述了最近的发现和新的见解是什么推动了 PFA 室管膜瘤，这是最常见的组。PFA 室管膜瘤的特点是诊断时的中位年龄年轻、基因组整体平衡和临床结果不佳（56% 的 10 年总生存期）。测序研究显示没有融合基因或其他高度反复突变的基因，这表明该疾病是表观遗传驱动的。确实，最近的研究结果表明，PFA 室管膜瘤中抑制性组蛋白 3 赖氨酸 27 三甲基化 (H3K27me3) 标记的特征性全局缺失是由 zeste 同源抑制蛋白 (EZHIP) 增强子的异常表达或在极少数情况下由 H3K27M 突变引起的，这两者都抑制 EZH2，从而阻止多梳抑制复合物 2 (PRC2) 扩散 H3K27me3。我们介绍了 EZHIP 正在进行的工作的现状及其在 PFA 生物学的表观遗传干扰中的重要作用。绘制了与癌组蛋白 H3K27M 及其在弥漫性中线胶质瘤 (DMG) 中的作用的比较，突出了肿瘤实体和潜在机制之间的相似性和差异。