Disruption of DNA methylation underpins the neuroinflammation induced by targeted CNS radiotherapy

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Targeted radiotherapy induces significant DNA methylation changes in peri-lesional brain tissue, impacting gene expression and contributing to neuroinflammation.
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The study identified 3194 differentially methylated regions, with 75% being hypomethylated in irradiated brain tissue, affecting various genomic locations.
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Irradiated samples showed increased microglia/macrophages and decreased peripheral immune cells, indicating a distinct inflammatory microenvironment.
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Cerebral organoid models demonstrated similar DNA methylation alterations and neuropeptide upregulation, supporting the role of epigenetic dysregulation in neurotoxicity.
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These findings suggest that targeting epigenetic changes may offer new strategies to mitigate side effects of radiotherapy in brain cancer patients.

Brain

by Thomas O Millner, Pratistha Panday, Yunchen Xiao, James G Nicholson, James R Boot, Zsharmaine Arpe, Paul A Stevens, Nadia N Rahman, Xinyu Zhang, Charles Mein, Neil Kitchen, Andrew W McEvoy, Edward McKintosh, Grainne S McKenna, Dimitrios Paraskevopoulos, Nicolae Radu Zabet, Rachel Lewis, Sara Badodi, Silvia Marino
April 29, 2025

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