Correlation of promoter hypermethylation in hTERT, DAPK and MGMT genes with cervical oncogenesis progression.
DNA hypermethylation occurs during the multistep process of cervical carcinogenesis. We investigated whether the methylation status in the promoter region of a potential oncogene, the human telomerase reverse transcriptase (hTERT), and the tumor suppressor genes death-associated protein kinase (DAPK) and O6-methylguanine DNA methyltransferase (MGMT), were able to distinguish the early from late stages of cervical oncogenesis. The methylation status in the promoter of these genes was analyzed using real-time MethyLight analysis in 115 cervical specimens, including normal, premalignant [atypical squamous epithelial cells (ASCUS), low-grade squamous intraepithelial lesions (LGSIL), high-grade squamous intraepithelial lesions (HGSIL)] and cancer specimens. Clinicopathological parameters (cytology, histology, grade, stage) were compared to the levels of promoter hypermethylation. We found that hTERT, MGMT and DAPK hypermethylation levels were increased during cervical oncogenesis progression. hTERT promoter hypermethylation was able to distinguish normal from cancer (p=0.008), normal from premalignant (p=0.036), as well as premalignant from cervical cancer cases (p=0.003). A significant association was also observed between all three genes and the grade of cervical cancer, with hTERT showing a better association (p<0.0001). Our data suggest that the combination of hTERT, MGMT, DAPK promoter hypermethylation could have a potential function as molecular biomarker of cervical oncogenesis progression.
Iliopoulos
Dimitrios
D
Institute of Biomedical Research and Technology, Larissa, Greece.
Oikonomou
Pagona
P
Messinis
Ioannis
I
Tsezou
Aspasia
A
D000293:Adolescent; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D064550:Death-Associated Protein Kinases; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
D051017:Apoptosis Regulatory Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C509186:TERT protein, human; D019098:Telomerase; D045643:DNA Repair Enzymes