Promoter methylation status of hMLH1, MGMT, and CDKN2A/p16 in colorectal adenomas
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Psofaki, V.
Kalogera, C.
Tzambouras, N.
Stephanou, D.
Tsianos, E.
Seferiadis, K.
Kolios, G.
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peer-reviewed
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World J Gastroenterol
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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 (tubular 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 relation 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 progression 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, CDKN2A/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.
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Adaptor Proteins, Signal Transducing/*genetics, Adenoma/*genetics/physiopathology, Aged, Colorectal Neoplasms/*genetics/physiopathology, CpG Islands/genetics, Cyclin-Dependent Kinase Inhibitor p16/*genetics, DNA Methylation/*physiology, DNA Modification Methylases/*genetics, DNA Repair Enzymes/*genetics, Disease Progression, Female, Humans, Male, Microsatellite Repeats/genetics, Middle Aged, Nuclear Proteins/*genetics, Promoter Regions, Genetic/*genetics, Tumor Suppressor Proteins/*genetics
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http://www.ncbi.nlm.nih.gov/pubmed/20653064
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en
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Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής