Department of Neurosurgery, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany.
Institute of Neuropathology, University Hospital Münster, Pottkamp 2, Münster, North Rhine-Westphalia, Germany.
Neurosurg Rev. 2020 Jun;43(3):903-910. doi: 10.1007/s10143-019-01087-3. Epub 2019 Feb 20.
Telomerase activity and (human) Telomerase Reverse Transcriptase (hTERT) expression are considered hallmarks in oncogenesis of neoplasms and are upregulated by alterations of the hTERT promoter. In meningiomas, numerous studies investigated hTERT expression, telomerase activity, promoter mutations, and methylations. Moreover, reports about hTERT-targeted chemotherapy in meningiomas have recently been published. We provide a systematic review of the literature about the role of hTERT in meningiomas. TERT expression and telomerase activity is found in benign and high-grade meningiomas and increase with WHO grade. Remarkably, rates of TERT expression/telomerase activity usually exceed mutation frequency and both telomerase activity and TERT expression have also been found in hTERT promoter wildtype meningiomas, indicating further mechanisms of TERT upregulation. Although hTERT promoter methylation has been reported in the vast majority of meningiomas, correlation with TERT expression remains controversial. Rates of promoter mutations, and methylation were shown to increase with rising WHO grade. Moreover, promoter methylation and mutations strongly correlate with prognosis. Although mutations predicted malignant progression, de novo mutations in high-grade recurrences of former benign lesions were also observed. Retroviral transduction of the TERT gene enabled immortalization in several grade I-III meningioma cell lines. In vitro analyses revealed significant effects on viability in hTERT-mutated meningioma cells after targeted treatment. Alternative mechanisms of telomere lengthening are usually absent in meningiomas. TERT and hTERT promoter alterations play a major role during oncogenesis of meningiomas with implications for prognosis and potentially treatment.
端粒酶活性和（人）端粒酶逆转录酶（hTERT）表达被认为是肿瘤发生的标志，并且 hTERT 启动子的改变会导致其上调。在脑膜瘤中，许多研究调查了 hTERT 表达、端粒酶活性、启动子突变和甲基化。此外，最近也有关于脑膜瘤中 hTERT 靶向化疗的报告。我们对 hTERT 在脑膜瘤中的作用进行了系统的文献回顾。良性和高级别脑膜瘤中均发现 hTERT 表达和端粒酶活性增加，且随着 WHO 分级增加而增加。值得注意的是，hTERT 表达/端粒酶活性的发生率通常超过突变频率，并且 hTERT 启动子野生型脑膜瘤中也发现了端粒酶活性和 hTERT 表达，表明 hTERT 上调的进一步机制。尽管 hTERT 启动子甲基化在绝大多数脑膜瘤中均有报道，但与 hTERT 表达的相关性仍存在争议。随着 WHO 分级的升高，启动子突变和甲基化的发生率也有所增加。此外，启动子甲基化和突变与预后密切相关。尽管突变预测恶性进展，但在良性前病变的高级复发中也观察到了新的突变。TERT 基因的逆转录病毒转导使几种 I-III 级脑膜瘤细胞系实现了永生化。体外分析显示，在 hTERT 突变的脑膜瘤细胞中，靶向治疗后细胞活力有显著影响。端粒延长的替代机制通常不存在于脑膜瘤中。TERT 和 hTERT 启动子改变在脑膜瘤的发生过程中起主要作用，对预后和潜在的治疗有影响。
