Epigenetics of paediatric glioma stem cells; focusing on exosomes, miRNAs and DNA methylation

Tumours in the central nervous system are accountable for the majority of cancer-related deaths in children. Glioblastoma multiforme, one of the deadliest of the central nervous system tumours, is partly driven by glioma stem cells. The generation and maintenance of these cells is orchestrated by complex genetic and epigenetic mechanisms. This thesis investigates the role of two epigenetic players, miRNAs and DNA methylation, as well as the involvement of exosomes in paediatric glioma stem cells. The first study profiles the miRNA content of these cells and compares it to normal neural stem cells. Furthermore, the miRNA content of the exosomes secreted by glioma stem cells and its effect on normal stem cells is determined. The second study investigates how specific miRNAs are regulated and how they could potentially influence glioma stem cells’ response to the chemotherapeutic agent temozolomide. These studies provide new insights into the multifaceted epigenetic regulation of glioma stem cells. The gained knowledge could lead to a better understanding of the biological processes behind brain tumours

Understanding the Epitranscriptome for Avant-Garde Brain Tumour 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