Uncovering the role of epigenetic changes in chromosomal structure in cancer
Cancer genomics allowed systematic mapping of oncogenic genetic alterations of genes. However, oncogenic epigenetic alterations of regulatory elements away from genes remain unknown. Recently, it was demonstrated that aberrant DNA methylation of CTCF binding sites perturbs chromosomal topology in IDH-mutant glioma and SDH-deficient gastrointestinal stromal tumours. Losing CTCF binding at the border between two topologically associating domains disrupts their insulation, leading to oncogene activation. This pioneering model connects metabolic, epigenetic and topological alterations demonstrating potential oncogenesis. The EU-funded CancerEpiTopology project will develop new statistical models and experimental approaches to systematically map and understand the regulation of DNA methylation at CTCF binding sites. It will show how its disruption in cancer leads to epigenetic heterogeneity and drives oncogenesis.
Fields of science
Funding SchemeERC-STG - Starting Grant
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