Epigenetic Regulation of Telomere Maintenance for Therapeutic Interventions in Gliomas

Genes
Elisabeth Naderlinger, Klaus Holzmann

Abstract

High-grade astrocytoma of WHO grade 4 termed glioblastoma multiforme (GBM) is a common human brain tumor with poor patient outcome. Astrocytoma demonstrates two known telomere maintenance mechanisms (TMMs) based on telomerase activity (TA) and on alternative lengthening of telomeres (ALT). ALT is associated with lower tumor grades and better outcome. In contrast to ALT, regulation of TA in tumors by direct mutation and epigenetic activation of the hTERT promoter is well established. Here, we summarize the genetic background of TMMs in non-malignant cells and in cancer, in addition to clinical and pathological features of gliomas. Furthermore, we present new evidence for epigenetic mechanisms (EMs) involved in regulation of ALT and TA with special emphasis on human diffuse gliomas as potential therapeutic drug targets. We discuss the role of TMM associated telomeric chromatin factors such as DNA and histone modifying enzymes and non-coding RNAs including microRNAs and long telomeric TERRA transcripts.

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Citations

May 13, 2018·Genes·Tiago Bordeira GasparJoão Vinagre
Dec 24, 2017·Journal of Experimental & Clinical Cancer Research : CR·Luca PompiliErica Salvati
Jan 12, 2020·Current Topics in Medicinal Chemistry·Guilherme G da SilvaDiêgo M de Oliveira
Sep 25, 2020·Cellular and Molecular Life Sciences : CMLS·Omkar Suhas VinchureRitu Kulshreshtha
Apr 4, 2021·Cancers·Fatma Dogan, Nicholas R Forsyth
Mar 25, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Larissa Alexsandra da Silva Neto TrajanoAdenilson de Souza da Fonseca

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Methods Mentioned

BETA
Assay
acetylation
exome sequencing
transcription profiling

Software Mentioned

ALT
TA

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