Promoter methylation status of hMLH1,MGMT,and CDKN2A/p16 in colorectal adenomas

被引:18
|
作者
Vasiliki Psofaki [1 ]
Chryssoula Kalogera [2 ]
Nikolaos Tzambouras [3 ]
Dimitrios Stephanou [4 ]
Epameinondas Tsianos [3 ]
Konstantin Seferiadis [2 ]
Georgios Kolios [2 ]
机构
[1] Laboratory of Clinical Chemistry,University of Ioannina Medical School,45500 Ioannina,Greece
[2] Laboratory of Biochemistry,University Hospital of Ioannina,Leoforos S.Niarchou,45500 Ioannina,Greece
[3] Hepatogastroenterology Unit of Internal Medicine,University Hospital of Ioannina,Leoforos S.Niarchou,45500 Ioannina,Greece
[4] Laboratory of Pathology,University Hospital of Ioannina,Leoforos S.Niarchou,45500 Ioannina,Greece
关键词
Promoter methylation; Microsatellite instability; Human DNA mismatch repair gene mutator L homologue 1; O-6-methylguanine DNA methyltransferase; Cyclin-dependent kinase inhibitor 2A;
D O I
暂无
中图分类号
R735.3 [肠肿瘤];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:3553 / 3560
页数:8
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