Understanding the Epitranscriptome for Avant-Garde Brain Tumour Diagnostics

Abstract

RNA modifications are diverse, dynamic, and reversible transcript alterations rapidly gaining attention due to their newly defined RNA regulatory roles in cellular pathways and pathogenic mechanisms. The exciting emerging field of ‘epitranscriptomics’ is predominantly centred on studying the most abundant mRNA modification, N6-methyladenine (m6A). The m6A mark, similar to many other RNA modifications, is strictly regulated by so-called ‘writer’, ‘reader’, and ‘eraser’ protein species. The abundance of genes coding for the expression of these regulator proteins and m6A levels shows great potential as diagnostic and predictive tools across several cancer fields. This review explores our current understanding of RNA modifications in glioma biology and the potential of epitranscriptomics to develop new diagnostic and predictive classification tools that can stratify these highly complex and heterogeneous brain tumours.

Advancements in Image-Based Models for High-Grade Gliomas Might Be Accelerated

“…Prognostic tests that can be carried out on liquid biopsies from which circulating cells, circulating DNA and RNA can be analyzed are under investigation, but truly informative markers for the prognosis of HGG patients are sparse [149,150]. Modified RNAs that are important factors in the metabolic cooperation between HGG and TME [151,152] have been proposed as diagnostic and prognostic markers. However, those results require large validating multicenter clinical studies [153].…”

The epitranscriptome of high-grade gliomas: a promising therapeutic target with implications from the tumor microenvironment to endogenous retroviruses

“…However, we have yet to observe any tangible improvement in either clinical management or patient outcomes. A potential utility of epitranscriptomics is to be used in conjunction with known glioma sub-entities to further advance tumor stratification and help guide treatment selection [ 15 ]. According to studies mining the Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Repository for Molecular Brain Neoplasia Data (REMBRANDT), epitranscriptomic regulators appear to be differentially expressed based upon molecular alterations and clinical attributes.…”

“…The writers that catalyze this modification include methyltransferase enzymes methyltransferase-like 3 (METTL3), METTL14, and Wilms tumor 1-associated protein (WTAP) [ 14 ]. Examples of erasers that remove them are fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5) [ 15 ]. Readers involved in the m6A physiologic functions usually comprise the YT521-B homology (YTH) domain family of proteins or the heterogeneous nuclear ribonucleoprotein (HNRNP) proteins [ 9 ].…”