Mapping chromatin remodelling in glioblastoma identifies epigenetic regulation of key molecular pathways and novel druggable targets

Abstract Background Glioblastoma is the most common and aggressive malignant brain tumour in the adult population and its prognosis is dismal. The heterogeneous nature of the tumour, to which epigenetic dysregulation significantly contributes, is among the main therapeutic challenges of the disease....

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Main Authors: Claire Vinel, James Boot, Weiwei Jin, Nicola Pomella, Alexandra Hadaway, Charles Mein, Nicolae Radu Zabet, Silvia Marino
Format: Article
Language:English
Published: BMC 2025-02-01
Series:BMC Biology
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Online Access:https://doi.org/10.1186/s12915-025-02127-9
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Summary:Abstract Background Glioblastoma is the most common and aggressive malignant brain tumour in the adult population and its prognosis is dismal. The heterogeneous nature of the tumour, to which epigenetic dysregulation significantly contributes, is among the main therapeutic challenges of the disease. Results We have leveraged SYNGN, an experimental pipeline enabling the syngeneic comparison of glioblastoma stem cells and expanded potential stem cell (EPSC)-derived neural stem cells to identify regulatory features driven by chromatin remodelling specifically in glioblastoma stem cells. Conclusions We show epigenetic regulation of the expression of genes and related signalling pathways contributing to glioblastoma development. We also identify novel epigenetically regulated druggable target genes on a patient-specific level, including SMOX and GABBR2.
ISSN:1741-7007