Telomerase activity, TERT expression, hTERT promoter alterations, and alternative lengthening of the telomeres (ALT) in meningiomas – a systematic review
Telomerase activity, TERT expression, hTERT promoter alterations, and alternative lengthening of the telomeres (ALT) in meningiomas – a systematic review
复制标题
脑膜瘤中端粒酶活性、TERT 表达、hTERT 启动子改变和端粒 (ALT) 替代延长——系统评价
作者：
Louise Stögbauer;W. Stummer;V. Senner;B. Brokinkel
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，并且通过 hTERT 启动子的改变而上调。在脑膜瘤中，大量研究调查了 hTERT 表达、端粒酶活性、启动子突变和甲基化。此外，最近还发表了有关脑膜瘤hTERT靶向化疗的报道。我们对有关 hTERT 在脑膜瘤中的作用的文献进行了系统回顾。 TERT 表达和端粒酶活性存在于良性和高级别脑膜瘤中，并随着 WHO 分级而增加。值得注意的是，TERT 表达/端粒酶活性的比率通常超过突变频率，并且在 hTERT 启动子野生型脑膜瘤中也发现了端粒酶活性和 TERT 表达，这表明 TERT 上调的进一步机制。尽管在绝大多数脑膜瘤中都报道了 hTERT 启动子甲基化，但与 TERT 表达的相关性仍然存在争议。启动子突变率和甲基化率随着 WHO 等级的提高而增加。此外，启动子甲基化和突变与预后密切相关。尽管突变预示着恶性进展，但也观察到了以前良性病变高度复发的新生突变。 TERT 基因的逆转录病毒转导使几种 I-III 级脑膜瘤细胞系能够永生化。体外分析显示，靶向治疗后，hTERT 突变脑膜瘤细胞的活力受到显着影响。脑膜瘤通常不存在端粒延长的替代机制。 TERT 和 hTERT 启动子改变在脑膜瘤的肿瘤发生过程中发挥着重要作用，对预后和潜在的治疗具有影响。
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.
影响因子：
12.7
作者：
Juratli, Tareq A.;McCabe, Devin;Brastianos, Priscilla K.
通讯作者：
Brastianos, Priscilla K.
影响因子：
6
作者：
Heaphy, Christopher M.;Subhawong, Andrea P.;Meeker, Alan K.
通讯作者：
Meeker, Alan K.