KangDa College of Nanjing Medical University, Nanjing, China.
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
CNS Neurosci Ther. 2017 Oct;23(10):790-797. doi: 10.1111/cns.12724. Epub 2017 Sep 3.
The purpose of this study was to explore the clinical significance of telomerase reverse transcriptase (TERT) promoter mutations in gliomas.
We used DNA sequencing data to analyze 887 gliomas for TERT promoter mutations based on histological and genetic backgrounds. TERT promoter mutations were detected in 39.6% of low-grade gliomas, 40.3% of anaplastic gliomas, 44.7% of primary glioblastomas, 29.4% of secondary glioblastomas, and in 29.7% of Proneural, 38.6% of Neural, 41.8% of Classical, and 41.6% of Mesenchymal subtypes. Frequency of C250T mutation in recurrent gliomas was approximately half that in newly diagnosed gliomas. TERT exhibited improved prognosis when co-occurred with isocitrate dehydrogenase 1 (IDH1) and 1p19q alteration, but experienced inverse survival in the Mesenchymal subtype or tumor protein p53 (TP53) and epidermal growth factor receptor (EGFR) alteration. Furthermore, the five subtypes were classified based on the prognostic impact of the TERT mutation with different genetic backgrounds of glioma.
We describe the TERT promoter mutation spectrum according to the histological, genetic, and molecular subtypes of glioma, which may aid in glioma subtype classification and have clinical implications.
本研究旨在探讨端粒酶逆转录酶（TERT）启动子突变在脑胶质瘤中的临床意义。
我们使用 DNA 测序数据，根据组织学和遗传学背景，分析了 887 例脑胶质瘤中 TERT 启动子突变。低级别胶质瘤中检测到 TERT 启动子突变的比例为 39.6%，间变性胶质瘤为 40.3%，原发性胶质母细胞瘤为 44.7%，继发性胶质母细胞瘤为 29.4%，神经前体细胞型为 29.7%，神经型为 38.6%，经典型为 41.8%，间充质型为 41.6%。复发性脑胶质瘤中 C250T 突变的频率约为初诊脑胶质瘤的一半。TERT 与异柠檬酸脱氢酶 1（IDH1）和 1p19q 改变同时存在时预后改善，但在间充质亚型或肿瘤蛋白 p53（TP53）和表皮生长因子受体（EGFR）改变时生存情况相反。此外，还根据 TERT 突变与胶质瘤不同遗传背景的预后影响，对五种亚型进行了分类。
我们根据脑胶质瘤的组织学、遗传学和分子亚型描述了 TERT 启动子突变谱，这可能有助于脑胶质瘤亚型分类，并具有临床意义。
