Paper Details

Methylation profile of promoter region determined level of MGMT mRNA expression in colorectal cancer

Jamshid Mehrzad, Mahdieh Mohammaditabr, Arezoo Sadat Khafi

DOI: https://dx.doi.org/10.12692/ijb/4.10.42-50

Int. J. Biosci. 4(10), 42-50. May, 2014. (PDF)

Abstract:

O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair enzyme that is important for colorectal to stay protected against DNA mutagenesis. The role of MGMT reduction or loss in colorectal tumorigenesis is complex but numerous studies have documented methylation of this gene can be regarded as an event in colorectal cancer. The aim of this study is to demonstration of correlation between methylation profile in promoter region of MGMT with MGMT expression level, CRC occurence and with demographic and clinocopathological characteristics of CRC. Methylation profile in promoter region of MGMT was assayed by methylation-specific polymerase chain reaction (MS-PCR) and MGMT gene expression was performed by real time quantitative PCR (qPCR). RNA from embedded paraffin sections of colorectal tissue (in 70 sporadic colorectal tumors as well as adjoining and normal tissue specimens) was reverse transcribed, quantified and analyzed. Aberrant promoter methylation of MGMT gene was detected in 23 (32.9%) of 70 tumor samples and in 5 (7.1%) adjacent normal tissues. Thus, aberrant promoter methylation of MGMT is significantly correlated with CRC occurance. Aberrant promoter methylation was not found significantly associated with tumor stage and other clinocopathological and demographic characteristics. MGMT expression level in tumor tissues was 7.2-fold less than normal adjacent tissues. In conclusion, this study has identified aberrant promoter methylation of MGMT was significantly correlated with CRC, because aberrant promoter methylation effects on MGMT expression. Our assay demonstrated MGMT can be as a potential biomarker for CRC as diagnostic, prognostic and therapeutic targets in the future.