Aberrant Methylation Profile and Microsatellit Instability in Turkish Sporadic Colorectal Carcinoma

Abstract

Objective: Genomic DNA obtained from paraffin blocks of the intended colorectal cancer cases was evaluated for promoting colorectal cancer by investigating the promoter methylation of 6 different gene promoter regions and microsatellite instability. Methods: DNA was isolated from the paraffin tissue of 76 sporadic colorectal cancer patients by cross sections from the areas determined to be tumorous. The methylation specific PCR (MS-PCR) method was used for these DNA samples fo rmethlylation studies in promoter region of six different APC, hMLH1, p16INK4A, p15, p73 and DAPK1 genes. In the same samples, the presence of microsatellite instability (MSI). Results: The fequencey of methylation was 24\% for hMLH1, 31.5\% for APC, 19.6\% for DAPK1, 42.8\% for p16, 30\% for p15, 17\% for p73. We calculated a methylation index (MI=ratio between the number of genes methylated and the number of genes analyzed). MI was ranged from 0-0.83, with an average of 0.271 corresponding to 1.6 genes/sample and median was 0.225 and there were 15 samples which doesn't methylated in any loci. We analysed MSI in C-kit (21\%), hMSH2 (18\%) and APC (15\%), microsatellite region. Conclusion: We observed APC methylation was common then the other population for Turkish patient. P16 was the most commenest methylated loci among the 6 of gene and it seems storongly related with female patients. P73 was releated with left colorectal cancer and additionally it was related with the MSI.