DNMT inhibitors increase methylation at subset of CpGs in colon, bladder, lymphoma, breast, and ovarian, cancer genome

Abstract

AbstractBackgroundDNA methyltransferase inhibitors (DNMTi) decitabine and azacytidine are approved therapies for acute myeloid leukemia and myelodysplastic syndrome. Identification of CpGs violating demethylaion due to DNMTi treatment may help to understand their resistance mechanisms.Materials and MethodsTo identify such CpGs, we analysed publicly available 450K methylation data of multiple cancer type cell lines.ResultsWe identified 637 CpGs corresponding to genes enriched for p53 and olfactory receptor pathways with a transient increase in methylation (median Δβ = 0.12) after decitabine treatment in HCT116 cells. Azacytidine treatment also increased methylation of identified CpGs in 9 colon, 9 ovarian, 3 breast, and 1 lymphoma cancer cell lines.ConclusionDNMTi treatment increases methylation of subset of CpGs in cancer genome.