MGMT-B gene promoter hypermethylation in patients with inflammatory bowel disease - a novel finding.

Pooneh Mokarram,Mahvash Alizade Naini,Soudabeh Kavousipour,Golnosh Mehrabani,Mohammad Ali Fahmidehkar,Mostafa Moradi Sarabi,Abbas Alipour,Seyedeh Azra Shamsdin

doi:10.7314/apjcp.2015.16.5.1945

Pooneh Mokarram, Mahvash Alizade Naini + Show 6 more

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https://doi.org/10.7314/apjcp.2015.16.5.1945

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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.

Highlights

Inflammatory bowel disease (IBD) with at least two subtype diseases; ulcerative colitis (UC) and Crohn’s disease (CD) is strongly associated with uncontrolled chronic inflammation of intestines (Hartnett and Egan, 2012)
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
Distribution of selected IBD patients and controls According to clinical symptom, 52 patients were included from two referral hospitals in Shiraz, south of Iran in this study

Summary

Introduction

Inflammatory bowel disease (IBD) with at least two subtype diseases; ulcerative colitis (UC) and Crohn’s disease (CD) is strongly associated with uncontrolled chronic inflammation of intestines (Hartnett and Egan, 2012). Chronic Inflammation is thought to be the root cause of tumor development and associated with about 20% of all human cancers (Ullman and Itzkowitz, 2011; Hartnett and Egan, 2012). The most serious associated chronic complication of IBD is colorectal cancer (CRC); IBD patients are 60% more likely prone to develop CRC than general population with 10-15% mortality (Munkholm, 2003; Goel et al, 2011; Herrinton et al, 2012). In order to overcome such difficulties, intensive investigation are done by researchers to find noninvasive and good assessable diagnostic tools to be well-validated for early detection, prognosis and monitoring of precancerous state (Chambers et al, 2005; Mattar et al, 2011)

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