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

Background. Although mutations in the promoter region of the telomerase reverse transcriptase (TERTp) gene 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 =.034), and had shorter progression-free survival (7 vs. 10 months, respectively, P =.015) and overall survival (16 vs. 24 months, respectively, P =.017). Notably, magnetic resonance imaging performed showed that TERTp-mutant GBM was strongly associated with multifocal/distant lesions (P =.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.