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 ( TERT p) gene are the most common alterations in glioblastoma (GBM), their clinical significance remains unclear. Therefore, we investigated the impact of TERT p 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 TERT p 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 TERT p mutation were older at first diagnosis versus those with TERT p 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 TERT p-mutant GBM was strongly associated with multifocal/distant lesions ( P = .004). According to the CNA analysis, TERT p 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 TERT p mutations were strongly correlated with multifocal/distant lesions and poor prognosis in patients with IDH wild-type GBM. Less aggressive GBM with TERT p wild type may be a distinct clinical and molecular subtype of IDH wild-type GBM.