Is There an Independent Role of TERT and NF1 in High Grade Gliomas?

Razis, Evangelia and Kotoula, Vassiliki and Koliou, Georgia-Angeliki and Papadopoulou, Kyriaki and Vrettou, Eleni and Giannoulatou, Eleni and Tikas, Ioannis and Labropoulos, Stefanos V. and Rigakos, Georgios and Papaemmanoyil, Styliani and Romanidou, Ourania and Bourkoula, Eugenia and Nomikos, Panagiotis and Iliadis, Georgios and Nasioulas, George and Selviaridis, Panagiotis and Polyzoidis, Konstantinos and Fountzilas, George (2020) Is There an Independent Role of TERT and NF1 in High Grade Gliomas? Translational Oncology, 13 (2). pp.346-354. ISSN 19365233

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BACKGROUND: High grade glioma molecular profiling is of particular interest in neurooncology. The role of telomerase reverse transcriptase (TERT) varies dependent upon other molecular parameters. We explored the role of TERT in 101 high-grade gliomas. METHODS: A total of 101 patients (pts) with grade III-IV gliomas treated with standard of care and informative tumor genotypes were included in the present study. Of 55 genes targeted with the next-generation sequencing panel, mutations (muts) were found in 37; these were included in the analysis. TERT mut were tested with Sanger sequencing. MGMT promoter methylation status was determined by methylation specific PCR. RESULTS: 270 mut were detected in 92/101 tumors (91.1%). TERT was the most frequently mutated gene (74.3%). IDH1/2 mut were mutually exclusive with mut in the neurofibromin 1 (NF1) gene. Mutated TERT was associated with wild-type (wt) IDH1/2 (p = 0.025). The 12-month overall survival (OS) rate was 74.3% (median OS: 22 months). Pts with TERT and NF1 wt had a median OS of 40.8 months, while among pts with NF1 wt/TERT mutant, the median OS was 18.5 months. NF1 and TERT mut univariately conferred shorter OS (HR = 3.19; p = 0.004 and HR = 2.28; p = 0.002). Upon multivariate analysis, mutated TERT showed marginal unfavorable prognostic significance for OS (p = 0.049), while NF1 lost its unfavorable significance (p = 0.151). CONCLUSIONS: TERT is herein proven to confer poor prognosis in high grade gliomas, independent of IDH and MGMT. NF1 seems to also confer poor prognosis although our small numbers do not allow for firm conclusions.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 23 Jan 2020 04:17
Last Modified: 19 Oct 2021 01:04

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