Su1866 The CDx2 Homeoprotein Inhibits DNA Repair by Non-Homologous End Joining Specifically in Colon Cancer but Not in Leukemia Cells

activation of DNMT3b, the majority of the differentially methylated genes (83.2%, 886/ 1,065) were CpG hypermethylated in AGS-EBV cells as compared with AGS cells (foldchanges 2.43~65.2).Gene ontology analysis indicated that hypermethylated genes were enriched in the following KEGG pathways (≥10 genes each, P≤0.05): cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, axon guidance, regulation of actin cytoskeleton, insulin signaling pathway, cell adhesion molecules (CAMs), endocytosis, calcium signaling pathway, glutamatergic synapse and focal adhesion.Seven novel hypermethylated genes (MDGA2, IL15RA, OSR1, SCARF2, EPHB6, SSTR1 and REC8) were chosen for further validation.Our results revealed that all seven genes were down-regulated in AGS-EBV cells as compared with AGS cells.Demethylation treatment increased transcription levels of the seven genes in AGS-EBV cells.Dense methylation in the promoter of these candidates was further confirmed by BGS.Conclusions: EBV infection in AGS cells induced genome-wide aberrant promoter hypermethylation of 886 genes involving in several important cancer-related pathways.Induction of promoter methylation by EBV is regulated by upregulation of DNMT3b through LMP2A.