A27 DNA HYPOMETHYLATION INDUCED BY 5-AZA-CDR OR LOSS OF DNMT1 INHIBITS COLITIS-ASSOCIATED COLORECTAL CANCER

Abstract Background Colorectal cancer is the second leading cause of death in Canada. A major risk factor for development colorectal chronic inflammation to colitis-associated (CAC). We previously described a CAC mouse model which tumors arise from DCLK1+ tuft cells following loss tumor suppressor adenomatous polyposis coli (APC) and induction colitis. Interestingly, both colitis display epigenetic changes that modulate gene expression. However, impact DNA methylation on colonic tumorigenesis not known. Thus, we hypothesize inhibition reduces tumorigenesis. Purpose In this study, aim investigate role by inhibiting using genetic pharmacologic means. Method Using publicly available dataset (GSE75214) expression data analyzed microarray biopsies patients with ulcerative Crohn’s Disease active disease, examined methyltransferases (DNMTs). Expression DNMTs mice was additionally RT-qPCR global levels measured 5-mC ELISA. separate experiments, Dclk1-CreERT2/Apcf/f were crossed DNMT1f/f knock-out methyltransferase DNMT1 cells. Dclk1/Apcf/f Dclk1/Apcf/f/DNMT1f/f then administered three doses tamoxifen followed 2.5% dextran sodium sulfate (DSS) five days induce Fourteen weeks later, assessed number size. cohort mice, induced treated six de-methylating drug 5-AZA-2’-deoxycytidine (5-AZA) or vehicle, number. To examine changes, WT 5-AZA DSS isolated intestinal epithelial From cell, ran Infinium MouseMethylation BeadChip Array. Result(s) Patients IBD found have increased compared healthy controls. Mice similarly had expression, as well as, Deletion significantly inhibited size tumors. Treatment decreased specific levels, reduced tumors, average per mouse. Conclusion(s) Our findings demonstrate associated methylation. Furthermore, hypomethylation treatment formation suggesting altered plays critical Disclosure Interest None Declared