Detection of TERT Promoter Mutations as a Prognostic Biomarker in Gliomas: Methodology, Prospects, and Advances

Abstract

This article reviews the existing approaches to determining the TERT promoter mutational status in patients with various tumoral diseases of the central nervous system. The operational characteristics of the most common methods and their transferability in medical practice for the selection or monitoring of personalized treatments based on the TERT status and other related molecular biomarkers in patients with the most common tumors, such as glioblastoma, oligodendroglioma, and astrocytoma, are compared. The inclusion of new molecular markers in the course of CNS clinical management requires their rapid and reliable assessment. Availability of molecular evaluation of gliomas facilitates timely decisions regarding patient follow-up with the selection of the most appropriate treatment protocols. Significant progress in the inclusion of molecular biomarkers for their subsequent clinical application has been made since 2016 when the WHO CNS classification first used molecular markers to classify gliomas. In this review, we consider the methodological approaches used to determine mutations in the promoter region of the TERT gene in tumors of the central nervous system. In addition to classical molecular genetical methods, other methods for determining TERT mutations based on mass spectrometry, magnetic resonance imaging, next-generation sequencing, and nanopore sequencing are reviewed with an assessment of advantages and disadvantages. Beyond that, noninvasive diagnostic methods based on the determination of the mutational status of the TERT promoter are discussed.

Keywords: MRI; NGS; Sanger sequencing; TERT; TERT mutations; TERT promoter region; central nervous system tumors; dPCR; ddPCR; glioma; molecular biomarkers; noninvasive detection; telomerase activation; telomerase reverse transcriptase.

Figure 1

Schematic presentation of TERT gene at chromosome 5p, its promoter structure and two canonical mutations causing gliomagenesis. C > T mutation occurs at one of both positions of the TERTp (−124 and −146 to ATG for C228T and C250T, respectively) in gliomas, which create de novo ETS binding motifs. CC242/243TT is a rare mutation and has not previously been seen in gliomas; it has been observed in other types of cancer. The figure was created with BioRender.com (19 March 2021).