DNMT inhibitors increase methylation of CpGs related to p53 pathway genes in colon, lymphoma, bladder, ovarian, and breast cancer cells

Abstract

BackgroundDNA 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.\n\nMaterials and MethodsTo identify such CpGs, we analysed publicly available 450K methylation data of multiple cancer type cell lines.\n\nResultsWe identified 637 CpGs corresponding to genes enriched for p53 and olfactory receptor pathways with a transient increase in methylation (median {Delta}{beta} = 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.\n\nConclusionDNMTi treatment increases methylation of subset of CpGs in cancer genome.