PURPOSE OF INVESTIGATION: aberrant gene function and transcriptional silencing by CpG island hypermethylation have become a critical component in the initiation and progression of endometrial cancer. The aim of this study was to investigate the methylation status of genes associated with aberrant DNA hypermethylation in benign, premalignant and malignant endometrial lesions. METHODS: using nested methylation-specific PCR, we assessed the methylation of the promoter regions of two genes, hMLH1 and CDKN2A/p16, in tissue samples from endometrial polyps (EP), atypical hyperplasia (AH) and endometrial cancer (EC). RESULTS: the promoter region of at least one of the two genes was aberrantly methylated in EP (hMLH1 42%, CDKN2A/p16 16%), AH (hMLH1 16%, CDKN2A/p16 50%), EC (hMLH1 50%, CDKN2A/p16 75%). Interestingly, hypermethylation of both genes was found with significant increased frequence in AH and EC, but not in benign lesions. CONCLUSIONS: our preliminary findings seem to suggest that the association of the two genes hMLH1 and CDKN2A/p16 may allow a differential diagnosis between benign and premalignant/malignant endometrial lesions; this further supports the hypothesis that methylation of such DNA mismatch repair and tumour-suppressor genes may be associated with endometrial carcinogenesis thus representing a valuable target for selective pharmacologic therapy.
PURPOSE OF INVESTIGATION: aberrant gene function and transcriptional silencing by CpG island hypermethylation have become a critical component in the initiation and progression of endometrial cancer. The aim of this study was to investigate the methylation status of genes associated with aberrant DNA hypermethylation in benign, premalignant and malignant endometrial lesions. METHODS: using nested methylation-specific PCR, we assessed the methylation of the promoter regions of two genes, hMLH1 and CDKN2A/p16, in tissue samples from endometrial polyps (EP), atypical hyperplasia (AH) and endometrial cancer (EC). RESULTS: the promoter region of at least one of the two genes was aberrantly methylated in EP (hMLH1 42%, CDKN2A/p16 16%), AH (hMLH1 16%, CDKN2A/p16 50%), EC (hMLH1 50%, CDKN2A/p16 75%). Interestingly, hypermethylation of both genes was found with significant increased frequence in AH and EC, but not in benign lesions. CONCLUSIONS: our preliminary findings seem to suggest that the association of the two genes hMLH1 and CDKN2A/p16 may allow a differential diagnosis between benign and premalignant/malignant endometrial lesions; this further supports the hypothesis that methylation of such DNA mismatch repair and tumour-suppressor genes may be associated with endometrial carcinogenesis thus representing a valuable target for selective pharmacologic therapy.
Authors: J Bischoff; A Ignatov; A Semczuk; C Schwarzenau; T Ignatov; T Krebs; D Küster; D Przadka-Rabaniuk; A Roessner; S D Costa; R Schneider-Stock Journal: Clin Exp Metastasis Date: 2012-05-03 Impact factor: 5.150
Authors: Jamie N Bakkum-Gamez; Nicolas Wentzensen; Matthew J Maurer; Kieran M Hawthorne; Jesse S Voss; Trynda N Kroneman; Abimbola O Famuyide; Amy C Clayton; Kevin C Halling; Sarah E Kerr; William A Cliby; Sean C Dowdy; Benjamin R Kipp; Andrea Mariani; Ann L Oberg; Karl C Podratz; Viji Shridhar; Mark E Sherman Journal: Gynecol Oncol Date: 2015-02-10 Impact factor: 5.482
Authors: Krina T Zondervan; Nilufer Rahmioglu; Andrew P Morris; Dale R Nyholt; Grant W Montgomery; Christian M Becker; Stacey A Missmer Journal: Semin Reprod Med Date: 2016-08-11 Impact factor: 1.303