Barange Mukesh, Epari Sridhar, Gurav Mamta, Shetty Omshree, Sahay Ayushi, Shetty Prakash, Goda Jayantsastri, Moyiadi Aliasagar, Gupta Tejpal, Jalali Rakesh
Department of Pathology (Including Division of Molecular Pathology), Tata Memorial Hospital and ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra, India.
Department of Neurosurgical division of Surgical Oncology, Tata Memorial Hospital and ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra, India.
Neurol India. 2021 Jan-Feb;69(1):126-134. doi: 10.4103/0028-3886.310096.
Telomerase reverse transcriptase promoter (pTERT) mutation is a dominant altered telomere maintenance mechanism in primary glioblastomas (GBMs).
The aim of this study was to correlate pTERT mutations with clinico-histological features and other molecular markers (p53 protein-expression, ATRX protein-expression, IDH mutations, EGFR gene amplification and MGMT methylation) in adult GBMs.
Evaluated for histological patterns, p53 and ATRX protein expression by immunohistochemistry (IHC), IDH mutations by IHC followed by sequencing in IHC negative cases, EGFR gene amplification by fluorescence in situ hybridization, MGMT promoter methylation by methylation-specific PCR and pTERT mutation by sequencing.
A total of 155 adult supratentorial GBMs [age-range 20-80 years] formed study cohort. 15.6% were IDH1R132 mutated, none were IDH2R172 mutated and 27% were EGFR amplified. 43% were MGMT methylated and were more common with IDH-mutation (mIDH) than EGFR amplification. 90% of mIDH (but no EGFR amplified) cases showed ATRX-loss. 43.5% were pTERT mutated (C228T was the commonest type) and were mutually exclusive with ATRX-loss. 14% of mIDH and 42% of EGFR amplified cases showed pTERT mutation, the latter was more commonly pMGMT unmethylated (63.6%).
43.5% of the GBMs showed pTERT mutation (C228T was commonest; 72%). pTERT mutations were mutually exclusive with ATRX protein loss, more commonly associated with IDH wild type and EGFR amplified GBMs.
端粒酶逆转录酶启动子（pTERT）突变是原发性胶质母细胞瘤（GBM）中一种主要的端粒维持机制改变。
本研究旨在将pTERT突变与成人GBM的临床组织学特征及其他分子标志物（p53蛋白表达、ATRX蛋白表达、异柠檬酸脱氢酶（IDH）突变、表皮生长因子受体（EGFR）基因扩增和O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）甲基化）相关联。
通过免疫组织化学（IHC）评估组织学模式、p53和ATRX蛋白表达，对IHC阴性病例通过IHC检测IDH突变后进行测序，通过荧光原位杂交检测EGFR基因扩增，通过甲基化特异性PCR检测MGMT启动子甲基化，通过测序检测pTERT突变。
共155例成人幕上GBM[年龄范围20 - 80岁]组成研究队列。15.6%为IDH1 R132突变，无IDH2 R172突变，27%为EGFR扩增。43%为MGMT甲基化，且在IDH突变（mIDH）中比在EGFR扩增中更常见。90%的mIDH（但无EGFR扩增）病例显示ATRX缺失。43.5%为pTERT突变（C228T是最常见类型），且与ATRX缺失相互排斥。14%的mIDH和42%的EGFR扩增病例显示pTERT突变，后者更常见于pMGMT未甲基化（63.6%）。
43.5%的GBM显示pTERT突变（C228T最常见；72%）。pTERT突变与ATRX蛋白缺失相互排斥，更常见于IDH野生型和EGFR扩增的GBM。
