Division of Cancer and Cell Biology, Translational Genomics Research Institute, 445 N 5th Street, Phoenix, AZ, 85004, USA.
Curr Neurol Neurosci Rep. 2018 Mar 10;18(4):15. doi: 10.1007/s11910-018-0825-7.
High-throughput genomic sequencing has identified alterations in the gene encoding human telomerase reverse transcriptase (TERT) as points of interest for elucidating the oncogenic mechanism of multiple different cancer types, including gliomas. In gliomas, the TERT promoter mutation (TPM) and resultant overexpression of TERT are observed mainly in the most aggressive (primary glioblastoma/grade IV astrocytoma) and the least aggressive (grade II oligodendroglioma) cases. This article reviews recent research on (1) the mechanism of TERT activation in glioma, (2) downstream consequences of TERT overexpression on glioma pathogenesis, and (3) targeting TPMs as a therapeutic strategy.
New molecular classifications for gliomas include using TPMs, where the mutant group demonstrates the worst prognosis. Though a canonical function of TERT is established in regard to telomere maintenance, recent studies on non-canonical functions of TERT explore varied roles of telomerase in tumor progression and maintenance. Somatic alterations of the TERT promoter present a promising target for novel therapeutics development in primary glioma treatment.
高通量基因组测序已经确定了人端粒酶逆转录酶（TERT）基因的改变是阐明多种不同癌症类型（包括神经胶质瘤）致癌机制的关注点。在神经胶质瘤中，TERT 启动子突变（TPM）和 TERT 的过表达主要观察到在最具侵袭性（原发性胶质母细胞瘤/IV 级星形细胞瘤）和侵袭性最低（II 级少突胶质细胞瘤）的病例中。本文综述了 TERT 在神经胶质瘤中激活的机制、TERT 过表达对神经胶质瘤发病机制的下游影响以及将 TPM 作为治疗策略的最新研究进展。
神经胶质瘤的新分子分类包括使用 TPM，其中突变组的预后最差。尽管 TERT 的一个典型功能是维持端粒，但最近关于 TERT 的非典型功能的研究探索了端粒酶在肿瘤进展和维持中的多种作用。TERT 启动子的体细胞改变为原发性神经胶质瘤治疗的新型治疗药物的开发提供了一个很有前途的靶点。
