Abstract
Mutations in the telomerase reverse transcriptase gene promoter (TERTp) are common in glioblastomas (GBMs) and oligodendrogliomas (ODGs), and therefore, have a key role in tumorigenesis and may be of prognostic value. However, the extent of their prognostic importance in various gliomas is controversial. We studied 168 patients separated into five groups: Group 1: 65 patients with ODG carrying an IDH1 or IDH2 mutation (IDH-mutant) and 1p/19q–codeletion, Group 2: 23 patients with anaplastic astrocytoma (AA), IDH-mutant, Group 3: 13 patients with GBM, IDH-mutant, Group 4: 15 patients with AA, IDH-wildtype (WT), and Group 5: 52 patients with GBM, IDH-WT. TERTp mutations were found in 96.9%, 4.4%, 76.9%, 20.0%, and 84.6% of patients in Groups 1, 2, 3, 4, and 5, respectively. The R132H mutation in IDH1 was found in 60.5% (23/38) of patients in the AA cohort (Groups 2 and 4) and 20.0% (13/65) of patients from our GBM cohort (Groups 3 and 5), whereas all patients with ODG (Group 1) had a mutation either in IDH1 (n = 62) or IDH2 (n = 3). Using Kaplan Meier survival analysis, we found that the TERTp mutation was correlated with poor overall survival (OS) in Groups 2 and 4 combined (P = 0.001) and in Group 4 (P = 0.113), and in multivariate analysis, the TERTp mutant group was associated with significantly poor survival in Group 5 (P = 0.045). However, IDH mutation, MGMT methylation, and younger patient age (<55 years old) were significantly correlated with favorable OS (all P < 0.05) in our cohort of astrocytic and ODGs. In patients with ODG (Group 1), mutant IDH and TERTp did not have prognostic value because these mutations were universally present. Based on the revised 2016 WHO classification of gliomas, we found that TERTp mutation was frequently present in patients with GBM or ODG and because it was strongly correlated with poor survival outcome in patients with IDH-WT GBM in multivariate analysis, it may be of prognostic value in this subgroup of patients with gliomas.
Highlights
Gliomas are the most common primary malignant tumor of the central nervous system (CNS), and are comprised of diffuse astrocytic and oligodendroglial tumors (ODG)
There was no evidence of an association between telomerase reverse transcriptase gene promoter (TERTp) mutation and Isocitrate dehydrogenase (IDH) or Alpha-thalassemia/mental retardation syndrome X-linked (ATRX) mutation (ATRX loss) or O6 methylguanine-DNA methyltransferase promoter (MGMTp) methylation status, gender preference, or age preference in all patient groups except the patients with AA by Pearson χ2 test
In Group 4 (IDH-WT AA), we found that patients with TERTp-mutant tumor showed shorter median survival compared to patients with TERTp-WT tumors [median survival with 95% CI: 8.0 months (0.000– 20.002) vs. 18.1 months (0.000–46.107), respectively]; TERTp mutation status did not have an statistically significant effect on overall survival (OS) or Progression free survival (PFS) (Table 5, Fig. 5c and d), possibly because the number of TERTp mutant cases were too few to attain statistical significance (P = 0.113)
Summary
Gliomas are the most common primary malignant tumor of the central nervous system (CNS), and are comprised of diffuse astrocytic and oligodendroglial tumors (ODG). Significant research in the pathogenesis of gliomas revealed that various morphological phenotypes are related to underlying molecular genetic variations [4, 26]. The second most important genetic alteration is a co-deletion at chromosome regions 1p and 19q, which results from a chromosomal translocation t(1p;19q)(q10;p10), and is exclusively associated with ODGs and better prognosis [20]. Such examples demonstrate that the identification of new molecular genetic changes, which occur during glioma formation or development, are necessary to better guide clinical decision making
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
