The Place and Prognostic Value of TERT Promoter Mutation in Molecular Classification in Grade II-III Glial Tumors and Primary Glioblastomas

Abstract

Objective: Diffuse gliomas, the most common primary malignant brain tumors, have been classified by the World Health Organization as class II-IV gliomas. After 2016, two mutations in the promoter region of the telomerase reverse transcriptase (TERT) gene were identified in addition to the IDH, 1p / 19q, and ATRX status. Material and Method: We identified 84 patients with grade II-IV glioma with IDH, ATRX, 1p / 19q and TERT status. All tumor samples were subjected to molecular genetic screening (Sanger sequencing for IDH and TERT mutations, fluorescence in situ hybridization for 1p/19q status) after histological diagnosis (immunohistochemistry for IDH1 R132H, ATRX, and p53) for a more precise molecular diagnosis. The confidence intervals were calculated at the 95% confidence level, and differences at p < 0.05 were considered statistically significant. Results: Primary glioblastomas had the highest frequency of TERT promoter mutations (25 of 28, 89.2%, p=0.006) followed by oligodendrogliomas (29 of 35, 82.8%, p<0.001) while astrocytomas showed the lowest frequency (3 of 15, 20%, p=0.107), and the positivity significantly differed among these three groups (p<0.001). TERT promoter mutations were more frequent in patients older than 55 years of age at diagnosis (p=0.023). The group with TERT promoter mutations, and without IDH mutations showed the worst overall survival. However, the presence of both TERT promoter and IDH mutations, which resembled oligodendroglial progression, showed best overall survival (p=0.042). Conclusion: The discovery of TERT promoter mutations in numerous gliomas has opened the door for a better molecular classification of gliomas, and TERT status is associated with survival. Further studies will help in elucidating the value of TERT promoter mutations as biomarkers in clinical practice, and eventual therapeutic targets.

Keywords

• diffuse glioma
• primary glioblastoma
• tert p
• promoter mutation
• survival