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.
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 carcinomapatients 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 cancerpatients, 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 cancerpatients 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.
Authors: M E Martínez; R Sampliner; J R Marshall; A K Bhattacharyya; M E Reid; D S Alberts Journal: Gastroenterology Date: 2001-04 Impact factor: 22.682
Authors: J R Jass; K G Biden; M C Cummings; L A Simms; M Walsh; E Schoch; S J Meltzer; C Wright; J Searle; J Young; B A Leggett Journal: J Clin Pathol Date: 1999-06 Impact factor: 3.411
Authors: Päivi Laiho; Virpi Launonen; Päivi Lahermo; Manel Esteller; Mingzhou Guo; James G Herman; Jukka-Pekka Mecklin; Heikki Järvinen; Pertti Sistonen; Kyoung-Mee Kim; Darryl Shibata; Richard S Houlston; Lauri A Aaltonen Journal: Cancer Res Date: 2002-02-15 Impact factor: 12.701
Authors: A Loukola; K Eklin; P Laiho; R Salovaara; P Kristo; H Järvinen; J P Mecklin; V Launonen; L A Aaltonen Journal: Cancer Res Date: 2001-06-01 Impact factor: 12.701
Authors: Zsolt Petko; Mahan Ghiassi; Anthony Shuber; Janice Gorham; Walter Smalley; M Kay Washington; Stephen Schultenover; Shiva Gautam; Sanford D Markowitz; William M Grady Journal: Clin Cancer Res Date: 2005-02-01 Impact factor: 12.531
Authors: S Veganzones; M L Maestro; S Rafael; V de la Orden; M Vidaurreta; B Mediero; M Espantaleón; J Cerdán; E Díaz-Rubio Journal: Tumour Biol Date: 2015-01-10