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

Background: Although mutations in the promoter region of the telomerase reverse transcriptase (p) gene are the most common alterations in glioblastoma (GBM), their clinical significance remains unclear. Therefore, we investigated the impact of 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 () or gene mutations were excluded from this study. Among the 147 cases of wild-type GBM, 92 (62.6%) had the p mutation. Clinical, immunohistochemical, and genetic factors (, gene mutation, CD133, ATRX expression, -methylguanine-DNA methyltransferase [] promoter methylation) and copy number alterations (CNAs) were investigated.

Results: GBM patients with the p mutation were older at first diagnosis versus those with p wild type (66.0 vs. 60.0 years, respectively, = .034), and had shorter progression-free survival (7 vs. 10 months, respectively, = .015) and overall survival (16 vs. 24 months, respectively, = .017). Notably, magnetic resonance imaging performed showed that p-mutant GBM was strongly associated with multifocal/distant lesions ( = .004). According to the CNA analysis, p mutations were positively correlated with amp/gain, deletion, and deletion; however, these mutations were negatively correlated with amp/gain, gain, and deletion.

Conclusions: p mutations were strongly correlated with multifocal/distant lesions and poor prognosis in patients with wild-type GBM. Less aggressive GBM with p wild type may be a distinct clinical and molecular subtype of wild-type GBM.