论文部分内容阅读
AIM:To investigate aberrant DNA methylation of CpG islands and subsequent low-or high-level DNA microsatellite instability(MSI)which is assumed to drive colon carcinogenesis. METHODS:DNA of healthy individuals,adenoma(tu-bular or villous/tubulovillous)patients,and colorectal carcinoma patients who underwent colonoscopy was used for assessing the prevalence of aberrant DNA methylation of human DNA mismatch repair gene mutator L homologue 1(hMLH1),Cyclin-dependent kinase inhibitor 2A(CDKN2A/p16),and O-6-methylguanine DNA methyltransferase(MGMT),as well as their rela- tion to MSI. RESULTS:The frequency of promoter methylation for each locus increased in the sequence healthy tissue/adenoma/carcinoma.MGMT showed the highest frequency in each group.MGMT and CDKN2A/p16 presented a statistically significant increase in promoter methylation between the less and more tumorigenic forms of colorectal adenomas(tubular vs tubullovillous and villous adenomas).All patients with tubulovillous/villous adenomas,as well as all colorectal cancer patients,showed promoter methylation in at least one of the examined loci.These findings suggest a potentially crucial role for methylation in the polyp/adenoma to cancer progres- sion in colorectal carcinogenesis.MSI and methylation seem to be interdependent,as simultaneous hMLH1, CDKN2A/p16,and MGMT promoter methylation was present in 8/9 colorectal cancer patients showing the MSI phenotype. CONCLUSION:Methylation analysis of hMLH1,CD- KN2A/p16,and MGMT revealed specific methylation profiles for tubular adenomas,tubulovillous/villous adenomas,and colorectal cancers,supporting the use of these alterations in assessment of colorectal tumorigenesis.
METHODS: DNA of healthy individuals, adenoma (tu-bular or villous / tubulovillous) patients , and colorectal carcinoma patients who underwent colonoscopy was used for assessing the prevalence of aberrant DNA methylation of human DNA mismatch repair gene mutator L homologue 1 (hMLH1), Cyclin-dependent kinase inhibitor 2A (CDKN2A / p16), and O-6-methylguanine DNA methyltransferase (MGMT), as well as their rela- tionship to MSI. RESULTS: The frequency of promoter methylation for each locus increased in the sequence healthy tissue / adenoma / carcinoma. MGMT showed the highest frequency in each group. MGMT and CDKN2A / p16 presented a resistance significant increase in promoter methylation between the less and more tumorigenic forms of colorectal adenomas (tuberculosis vs tubullovillous and villous adenomas). All patients with tubulovillous / villous a denomas, as well as all of colorectal cancer patients, showed promoter methylation in at least one of the examined loci. the findings suggest a potentially crucial role for methylation in the polyp / adenoma to cancer progres- sion in colorectal carcinogenesis. MSI and methylation seem to CONCLUSION: Methylation analysis of hMLH1, CD-KN2A / p16, and MGMT revealed specific methylation profiles for tubular adenomas, tubulovillous / villous adenomas, and colorectal cancers, supporting the use of these alterations in assessment of colorectal tumorigenesis.