MGMT-B Gene Promoter Hypermethylation in Patients with Inflammatory Bowel Disease - A Novel Finding


Inflammatory bowel disease (IBD) is a disease strongly associated with colorectal cancer (CRC) as a wellknownprecancerous condition. Alterations in DNA methylation and mutation in K-ras are believed to play anearly etiopathogenic role in CRC and may also an initiating event through deregulation of molecular signaling.Epigenetic silencing of APC and SFRP2 in the WNT signaling pathway may also be involved in IBD-CRC.The role of aberrant DNA methylation in precancerous state of colorectal cancer (CRC) is under intensiveinvestigation worldwide. The aim of this study was to investigate the status of promoter methylation of MGMTB,APC1A and SFRP2 genes, in inflamed and normal colon tissues of patients with IBD compared with controlnormal tissues. A total of 52 IBD tissues as well as corresponding normal tissues and 30 samples from healthyparticipants were obtained. We determined promoter methylation status of MGMT-B, SFRP2 and APC1A genesby chemical treatment with sodium bisulfite and subsequent MSP. The most frequently methylated locus wasMGMT-B (71%; 34 of 48), followed by SFRP2 (66.6 %; 32 of 48), and APC1A (43.7%; 21 of 48). Our studydemonstrated for the first time that hypermethylation of the MGMT-B and the SFRP2 gene promoter regionsmight be involved in IBD development. Methylation of MGMT-B and SFRP2 in IBD patients may provide amethod for early detection of IBD-associated neoplasia.