HMLH1 promoter methylation and JC virus T antigen presence in the tumor tissue of colorectal cancer Israeli patients of different ethnic groups

Background: Hypermethylation of tumor suppressor gene's promoter and JC virus infection may be etiologic factors in the development of colorectal cancer (CRC). Objevtives: To look at both JC virus T antigen and hMLH1 promoter methylation in CRC tissue in Israeli ethnic groups with different incidence of CRC. Methods: Twenty-four consecutive patients with sporadic CRC were included in the study. Genomic DNA was isolated from paraffin-embedded microdomains removed from five slides of 7- μm by deparaffinizing in multiple xylene washes. Isolated DNA was used as a template for PCR to amplify DNA sequences coding the amino terminus of JC virus T antigen. Methylation-specific PCR was performed on bisulfite-modified DNA templates from CRC tissue materials to study methylation status of hMLH1 promoter, using two sets of primers specific for amplification of methylated and unmethylated alleles. Results: hMLH1 promoter methylation was observed in five patients (20.8%) who were also positive for JC virus T antigen, with even distribution among the ethnic groups. JC virus T antigen DNA was found in cancer tissues of 20 of the 24 patients; 50, 90.9, and 100% of Asia-Africa-born Jews, Europe-America-born Jews, and Israeli Arabs, respectively (P = 0.036 between the first group to the other). Conclusion: Evidence for higher JC virus infection was shown among Europe-America-born Jews and Israeli Arabs. hMLH1 promoter methylation was evenly distributed between different ethnic groups in Israel.