TERT promoter mutation associated with multifocal phenotype and poor prognosis in patients with IDH wild-type glioblastoma

Abstract

Background Although mutations in the promoter region of the telomerase reverse transcriptase gene (TERTp) are the most common alterations in glioblastoma (GBM), their clinical significance remains unclear. Therefore, we investigated the impact of TERTp status on patient outcome and clinicopathological features in patients with GBM over a long period of follow-up Methods We retrospectively analyzed 153 cases of GBM. Six patients with isocitrate dehydrogenase 1 (IDH1) or H3F3A gene mutations were excluded from this study. Among the 147 cases of IDH wild-type GBM, 92 (62.6%) had the TERTp mutation. Clinical, immunohistochemical, and genetic factors (BRAF, TP53 gene mutation, CD133, ATRX expression, O 6-methylguanine-DNA methyltransferase [MGMT] promoter methylation) and copy number alterations (CNAs) were investigated Results GBM patients with the TERTp mutation were older at first diagnosis versus those with TERTp wild type (66.0 vs. 60.0 years, respectively, P=0.034), and had shorter progression-free survival (7 vs. 10 months, respectively, P=0.015) and overall survival (16 vs. 24 months, respectively, P=0.017). Notably, magnetic resonance imaging performed showed that TERTp-mutant GBM was strongly associated with multifocal/distant lesions (P=0.004)According to the CNA analysis, TERTp mutations were positively correlated with EGFR amp/gain, CDKN2A deletion, and PTEN deletion; however, these mutations were negatively correlated with PDGFR amp/gain, CDK4 gain and TP53 deletion Conclusions TERTp mutations were strongly correlated with multifocal/distant lesions and poor prognosis in patients with IDH wild-type GBM. Less aggressive GBM with TERTp wild type may be a distinct clinical and molecular subtype of IDH wild type GBM.

Detection of EGFR Mutation Distribution and Transcriptional Variants in IDH-wildtype High-grade Gliomas using a Next-generation Sequencing Oncopanel

“…The frequency of EGFR alterations in our cohort was lower than that in TCGA and MSKCC cohorts. However, a study from Japan reported that 25.5-33.1% of GBMs have EGFR ampli cations [19,20], which is consistent with our ndings. Recent reports indicate that 14.4-26% GBMs harbor EGFR mutations [2,21]; however, the EGFR mutation frequency in GBMs in our cohort (6.0%) was considerably lower than that in the previous study cohort.…”

Molecular analyses of rosette-forming glioneuronal tumor of the midbrain tegmentum: A report of two cases and a review of the FGFR1 status in unusual tumor locations

“…[ 3 ] Moreover, TERT p mutation is a poor prognostic factor for glioblastoma. [ 6 , 19 ] At present, the clinical significance of TERT p mutation is unknown in RGNT. RGNT occasionally presents with spontaneous shrinkage,[ 16 ] as observed in Case 1 of the present study.…”

Primary glioblastoma of the cauda equina with molecular and histopathological characterization: Case report

“… 19 , 20 TERT promoter mutations have been associated with poor prognosis in IDH wild-type GBM. 21 The described cauda equina lesion thus contains several genetic features expected to facilitate GBM growth.…”