title: MGMT-B gene promoter hypermethylation in patients with inflammatory bowel disease - a novel finding.
abstract: Inflammatory bowel disease (IBD) is a disease strongly associated with colorectal cancer (CRC) as a well-known precancerous condition. Alterations in DNA methylation and mutation in K-ras are believed to play an early 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 intensive investigation worldwide. The aim of this study was to investigate the status of promoter methylation of MGMT-B, APC1A and SFRP2 genes, in inflamed and normal colon tissues of patients with IBD compared with control normal tissues. A total of 52 IBD tissues as well as corresponding normal tissues and 30 samples from healthy participants were obtained. We determined promoter methylation status of MGMT-B, SFRP2 and APC1A genes by chemical treatment with sodium bisulfite and subsequent MSP. The most frequently methylated locus was MGMT-B (71%; 34 of 48), followed by SFRP2 (66.6 %; 32 of 48), and APC1A (43.7%; 21 of 48). Our study demonstrated for the first time that hypermethylation of the MGMT-B and the SFRP2 gene promoter regions might be involved in IBD development. Methylation of MGMT-B and SFRP2 in IBD patients may provide a method for early detection of IBD-associated neoplasia.
authors.affiliation: Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran E-mail : alizadem@sums.ac.ir, malizadenaini@yahoo.com.
authors.forename: Pooneh
authors.initials: P
authors.lastname: Mokarram
authors.forename: Soudabeh
authors.initials: S
authors.lastname: Kavousipour
authors.forename: Mostafa Moradi
authors.initials: MM
authors.lastname: Sarabi
authors.forename: Golnosh
authors.initials: G
authors.lastname: Mehrabani
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Fahmidehkar
authors.forename: Seyedeh Azra
authors.initials: SA
authors.lastname: Shamsdin
authors.forename: Abbas
authors.initials: A
authors.lastname: Alipour
authors.forename: Mahvash Alizade
authors.initials: MA
authors.lastname: Naini
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C515491:MGMT protein, human