Glioblastoma is a complex and aggressive primary brain tumour that is rapidly fatal. Timely and accurate diagnosis is therefore crucial. Here, we explore the newly emerging field of epitranscriptomics to understand the modifications that occur on RNA molecules in the healthy and diseased brain, focusing on glioblastoma. RNA modifications are modulated by various regulators and are diverse, specific, reversible, and involved in many aspects of brain tumour biology. Epitranscriptomic biomarkers may therefore be ideal candidates for clinical diagnostic workflows. This review summarises the current understanding of epitranscriptomics and its clinical relevance in brain cancer diagnostics.

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.