Evaluation of Methylation of MGMT (O⁶-Methylguanine-DNA Methyltransferase) Gene Promoter in Sporadic Colorectal Cancer

Abstract

The DNA repair gene O⁶-methylguanine-DNA methyltransferase (MGMT) is frequently methylated in colorectal cancer (CRC). The aim of this study was to demonstrate that MGMT methylation may be one of the candidate mediators of field cancerization in the colon mucosa. Therefore, quantitative methylation-specific polymerase chain reaction was performed on tumor itself and additional samples of 5 and 10 cm away from the tumor in 40 CRC patients. Moreover, colon mucosa was examined from 30 cases with no evidence of cancer as a control. MGMT promoter methylation was present in 27.5% of colorectal tumor specimens. Tumors that showed MGMT promoter methylation had substantial MGMT promoter methylation in their normal adjacent mucosa. The methylation was also observed in 36.36% (4/11) of normal samples with MGMT promoter methylation in the adjacent tumors, in 20.79% (6/29) of samples without MGMT methylation in the adjacent tumors, and in 6.66% (2/30) of control samples (p<0.006 and p<0.001 respectively). Finally, the mean of MGMT methylation levels was significantly higher in the cancerous group than in the control group (6.25±1.702 vs. 0.086±0.036, p<0.001). Some CRCs arise from a field defect defined by epigenetic inactivation of MGMT. Detection of such abnormality may ultimately be useful in risk assessment for CRCs.

Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

“…Several previous reports of the literature suggest that MGMT hypermethylation results in gene silencing and increased rate of mutations in normal colonic mucosa that might represent an initiating step in the development of mismatch repair-deficient CRC. [22][23][24][25] We also observed an age-related increase in MGMT methylation in CRC tissues in agreement with previous reports by Tserga et al 26 that showed a correlation between age and MGMT promoter methylation in breast cancer specimens, and Menigatti et al 21 that showed an age related increase of MGMT methylation in healthy colonic mucosa samples. CDKN2A was methylated in 29% of CRC samples and both RASSF1A and hMLH1 in 16.8% of them; by contrast, they resulted methylated only in a few healthy mucosa tissues.…”

Applicability of HIN-1, MGMT and RASSF1A promoter methylation as biomarkers for detecting field cancerization in breast cancer

“…To the best of our knowledge, field cancerization due to MGMT promoter methylation has not been reported so far. MGMT field cancerization has, however, been detected in colorectal cancers [ 14 , 41 ] and oral squamous cell carcinomas [ 42 ]. Aberrant methylation in tissue adjacent to breast tumor has already been reported previously for RASSF1A [ 20 , 21 ] and HIN-1 [ 21 ].…”

Prognostic impact of MGMT promoter methylation and MGMT and CD133 expression in colorectal adenocarcinoma

“…Various authors have reported that MGMT methylation is a useful marker to detect early stages of CRC [34,35]. Kang et al .…”