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Is There an Independent Role of TERT and NF1 in High Grade Gliomas?
Translational Oncology ( IF 4.5 ) Pub Date : 2019-12-28 , DOI: 10.1016/j.tranon.2019.10.016
Evangelia Razis 1 , Vassiliki Kotoula 2 , Georgia-Angeliki Koliou 3 , Kyriaki Papadopoulou 4 , Eleni Vrettou 5 , Eleni Giannoulatou 6 , Ioannis Tikas 4 , Stefanos V Labropoulos 1 , Georgios Rigakos 1 , Styliani Papaemmanoyil 7 , Ourania Romanidou 8 , Eugenia Bourkoula 9 , Panagiotis Nomikos 10 , Georgios Iliadis 11 , George Nasioulas 9 , Panagiotis Selviaridis 12 , Konstantinos Polyzoidis 12 , George Fountzilas 13
Affiliation  

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.



中文翻译:

TERT和NF1在高级别胶质瘤中是否有独立作用?

背景:高级神经胶质瘤分子轮廓分析在神经肿瘤学中尤为重要。端粒酶逆转录酶(TERT)的作用取决于其他分子参数。我们探讨了TERT在101例高级神经胶质瘤中的作用。方法:本研究共纳入101例经标准护理和信息丰富的肿瘤基因型治疗的III–IV级神经胶质瘤患者。在下一代测序小组针对的55个基因中,有37个发现了突变(突变)。这些都包括在分析中。使用Sanger测序测试了TERT mut。通过甲基化特异性PCR确定MGMT启动子甲基化状态。结果:在92/101个肿瘤中检测到270 mut(91.1%)。TERT是最常见的突变基因(74.3%)。IDH1 / 2 mut与神经纤维蛋白1(NF1)基因中的mut互斥。突变的TERT与野生型(wt)IDH1 / 2相关(p  = 0.025)。12个月总生存(OS)率为74.3%(中位OS:22个月)。具有TERT和NF1 wt的患者的OS中位数为40.8个月,而具有NF1 wt / TERT突变体的患者的OS中位数为18.5个月。NF1和TERT mut单变量赋予较短的OS(HR = 3.19; p  = 0.004和HR = 2.28; p  = 0.002)。经过多因素分析,突变的TERT对OS的预后意义不佳(p  = 0.049),而NF1则对OS的预后意义不佳(p = 0.151)。结论:在本文中证明TERT独立于IDH和MGMT而在高级神经胶质瘤中预后不良。NF1似乎也预后不良,尽管我们的人数很少不能得出肯定的结论。

更新日期:2019-12-28
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