Association Between Type-specific HPV Infections and hTERT DNA Methylation in Patients with Invasive Cervical Cancer

Cancer Genomics Proteomics. 2016;13(6):483-491. doi: 10.21873/cgp.20011.

Abstract

Background: There exists limited information on the role of hTERT methylation, and its association with type-specific HPV infections in cervical cancer.

Materials and methods: Eighty-seven frozen samples were analyzed for type-specific HPV infection using a GP5+/GP6+ PCR-RLB assay (RLB). hTERT DNA methylation analysis was performed using a newly developed PCR-RLB-hTERT.

Results: Ninety-three percent of samples were HPV-positive and fifteen different types were detected. hTERT methylation analysis of region 1 revealed no methylation in 78.8% of the samples and partial methylation in 21.2%. In region two, 68.2% showed no methylation and 31.8% showed a pattern of partial methylation. An association between the alpha 9 and alpha 7 species with a pattern of no methylation of hTERT in the region 1 was established (p=0.02 and p=0.03, respectively).

Conclusion: Differences in patterns of methylation of the hTERT core promoter [region 1 (nt -208 to -1) and region 2 (nt +1 to +104) relative to first ATG] are related to the HPV species present.

Keywords: DNA methylation; papillomavirus infections; telomerase reverse transcriptase; uterine cervical neoplasms.

MeSH terms

  • DNA Methylation / genetics*
  • Female
  • HeLa Cells
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / pathogenicity
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / pathogenicity
  • Humans
  • Neoplasm Invasiveness / genetics
  • Papillomavirus Infections / classification
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / virology
  • Telomerase / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology

Substances

  • TERT protein, human
  • Telomerase