Journal Article

Unravelling the mosaic: Epigenetic diversity in glioblastoma

Constantinou, Myrianni, Lucchini, Sara, Marino, Silvia

2024

Overview

Glioblastoma is the most common primary malignant brain tumour. Despite decades of intensive research in the disease, its prognosis remains poor, with an average survival of only 14 months after diagnosis. The remarkable level of intra‐ and interpatient heterogeneity is certainly contributing to the lack of progress in tackling this tumour. Epigenetic dysregulation plays an important role in glioblastoma biology and significantly contributes to intratumour heterogeneity. However, it is becoming increasingly clear that it also contributes to intertumour heterogeneity, which historically had mainly been linked to diverse genetic events occurring in different patients. In this review, we explore how DNA methylation, chromatin remodelling, microRNA (miRNA) dysregulation, and long noncoding RNA (lncRNA) alterations contribute to intertumour heterogeneity in glioblastoma, including its implications for advanced tumour stratification, which is the essential first step for developing more effective patient‐specific therapeutic approaches. Glioblastoma is a malignant brain tumour characterised by prominent heterogeneity at both the intra‐ and interpatient level. Despite advances in the genetic and transcriptional stratification of patients, clinical outcomes have not improved. Here we review epigenetic dysregulation in glioblastoma, focusing on its contribution to interpatient heterogeneity with an emphasis on classification refinement and novel therapeutic approaches.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Animals / Antisense RNA / Biomarkers / Brain Cancer / Brain Neoplasms - genetics / Brain Neoplasms - pathology / Brain tumors / brain tumours / Cancer Therapies / cell‐of‐origin / Chromatin / Chromatin Assembly and Disassembly - genetics / Chromatin remodeling / Chromosomes / DNA / DNA methylation / DNA Methylation - genetics / Epigenesis, Genetic / Epigenetic inheritance / Epigenetics / Gene expression / Gene Expression Regulation, Neoplastic / Genetic aspects / Genetic diversity / Genomes / Glioblastoma / Glioblastoma - genetics / Glioblastoma - pathology / Glioblastoma multiforme / Glioma / Health aspects / Humans / interpatient heterogeneity / Medical research / Medicine, Experimental / Methylation / MicroRNA / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / miRNA / Mutation / Nervous system / Patients / Personalized Medicine / Prognosis / Review / RNA, Long Noncoding - genetics / RNA, Long Noncoding - metabolism / Stem cells / Tumors