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.

Loneliness, Depression, and Genetics in the Elderly: Prognostic Factors of a Worse Health Condition?

“…Thus, for instance, rs6265 (BDNF) only has an association in the “solos and depressed individuals” group and not in the solos group or in the depressed individuals group ( Table S4 available in Supplementary Materials ). Against the evolutionary models of loneliness, in which it is proposed that the presence of certain genetic variants would be responsible for a greater sensitivity to socioenvironmental factors and would lead to higher levels of loneliness [ 60 ], it seems that alleles of the SNPs related to changes in telomere length, such as those of SYT16 and BDNF, would play a more important role in the group of “solos and depressed individuals”. Several studies have demonstrated the association between depression and telomere shortening [ 138 , 139 ], although this association with the alleles of the SNP rs2487999 or rs12335203, identified among the solos group, is not confirmed in the group of “solos and depressed individuals”.…”

“…The maintenance of telomere length is key since excessive shortening would lead to the appearance of symptoms associated with premature aging, and aberrant activity could favor the immortality of malignant cells. In recent years, there has been a number of publications on the search for mutations in the TER (RNA sequence of telomerase) sequence and in the TERT (telomerase reverse transcriptase) gene in various pathologies such as Zinsser–Cole–Engmann syndrome, also called Dyskeratosis Congenita [ 58 ]; aplastic anemia [ 59 ]; different types of cancer such as glioblastoma [ 60 ], melanoma [ 61 ], thyroid carcinoma [ 62 ], and breast cancer [ 63 ], among others; idiopathic pulmonary fibrosis [ 64 ]; and atherosclerosis [ 65 ] and more. Carroll et al (2013) [ 66 ] observed that elderly people (65–84 years), both men and women, with less social support had shorter telomeres.…”

MRI radiomics model for predicting TERT promoter mutation status in glioblastoma

“…Pathological diagnosis was made according to the 2021 (fifth edition) classification criteria for central nervous system brain tumors. IDH and TERT mutation statuses were obtained by next-generation sequencing, as described elsewhere (Arita, Narita, Takami et al, 2013;Hasanau et al, 2022). in a ratio of 7:3.…”

Molecular Biomarkers and Recent Liquid Biopsy Testing Progress: A Review of the Application of Biosensors for the Diagnosis of Gliomas

“…TERT mutations occur mainly in the promoter region but rarely in the coding region [40,41], see Figure 3. Gene mutations of TERT promoter (TERTp) cause telomerase reactivation in approximately 90% of solid tumors.…”