متیلاسیون اگزون 1، ژن CDKN2A در نمونه‌های بلوک پارافینه سرطان روده بزرگ

Background: The molecular studies indicate some of the genes in the promoter region itself, will undergo methylation. Methylation of CpG islands in the promoter region of that cause silence or reduced expression of genes involved in cell growth pathways, which are colorectal cancer causing agents. Detection of methylation status can be used as a marker for cancer diagnosis and prediction of disease. CDKN2A tumor suppressor gene encodes a protein, which inhibit CDK 4/6 and loss of retinoblastoma protein phosphorylation (pRb) is involved. The purpose of this study was to investigate the molecular hypermethylation in exon 1 of CDKN2A gene in patients with colorectal cancer and normal subjects. Methods: In this case-control study, the study population consisted of 20 patients with colorectal cancer and 10 healthy persons. Samples in paraffin blocks were prepared in pathology department of Mehr Hospital, Tehran, Iran, from December 2010 to June 2012. Then, specific primers were designed for the methylation and Non-methylation of CDKN2A gene. To determine the level of exon 1 methylation of CDKN2A gene, methylation-specific polymerase chain reaction (MSP) method was performed. Results: In this study, hypermethylation in exon 1 of CDKN2A gene were observed in 80% of tumor tissues (16 cases) and 20% of normal tissues (2 cases). The patients aged older than 50 years, had a higher CDKN2A gene methylation and frequency than patients younger than 50 years old (66% vs 34%) (P<0/001). Conclusion: The result of this study has been confirmed the role of CDKN2A gene promoter methylation of CpG sites of colorectal cancer as the leading cause of colorectal cancer. These data suggest that epigenetic silencing via aberrant methylation of the CDKN2A promoter plays a critical role in the inactivation of this tumor suppressor gene in colorectal cancer and can be used as a marker for early detection and identification of potential applications.