TERTmonitor-qPCR Detection of TERTp Mutations in Glioma

Genes (Basel). 2023 Aug 25;14(9):1693. doi: 10.3390/genes14091693.

Abstract

Telomerase promoter (TERTp) mutations are frequently observed in various types of tumours and commonly characterised by two specific hotspots located at positions -124 and -146 upstream of the start codon. They enhance TERTp activity, resulting in increased TERT expression. In central nervous system (CNS) tumours, they are integrated as biomarkers, aiding in the diagnosis and with a role in prognosis, where, in some settings, they are associated with aggressive behaviour. In this study, we evaluated the performance of TERTmonitor for TERTp genotyping in a series of 185 gliomas in comparison to the traditional method, Sanger sequencing. Against the gold-standard Sanger method, TERTmonitor performed with a 97.8% accuracy. Inaccuracy was mainly due to the over-detection of variants in negative cases (by Sanger) and the presence of variants that can modify the chemistry of the probe detection. The distribution of the mutations was comparable to other series, with the -124 being the most represented (38.92% for Sanger and TERTmonitor) and more prevalent in the higher-grade tumours, gliosarcoma (50.00%) and glioblastoma (52.6%). The non-matched cases are debatable, as we may be dealing with the reduced sensitivity of Sanger in detecting rare alleles, which strengthens the use of the TERTmonitor. With this study, we present a reliable and rapid potential tool for TERTp genotyping in gliomas.

Keywords: CNS tumours; TERTmonitor; genotyping; gliomas; qPCR; telomerase promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression
  • Glioblastoma*
  • Glioma* / diagnosis
  • Glioma* / genetics
  • Humans
  • Mutation
  • Real-Time Polymerase Chain Reaction / methods
  • Telomerase* / genetics

Substances

  • Telomerase

Grants and funding

This study was funded by national funds by FCT—Fundação para a Ciência e Tecnologia, I.P., through a research contract to J.V. (2022.00276.CEECIND) and to the project PTDC/MED-ONC/0531/2021—CTRL + ALT + CEL: how ATRX controls an alternative program in the β-cell. This study is also part of the project “Institute for Research and Innovation in Health Sciences” (UID/BIM/04293/2019); the project “Cancer Research on Therapy Resistance: From Basic Mechanisms to Novel Targets”-NORTE-01-0145-FEDER-000051, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); and the project “The Porto Comprehensive Cancer Center” with the reference NORTE-01-0145-FEDER-072678—Consórcio PORTO.CCC—Porto.Comprehensive Cancer Center Raquel Seruca. Additional funding was obtained from project “2022-C05IO101-02—Agenda Illiance (Bosch, project nº 46)—PPS4—OLI health”, with reference C644919832-00000035, funded by PRR—Plano de Recuperação e Resiliência e pelos Fundos Europeus NextGenerationEU, através do sistema de incentivos «Agendas para a Inovação Empresarial».