Importance of Cadherins Methylation in Ovarian Cancer: a Next Generation Sequencing Approach

Pathol Oncol Res. 2019 Oct;25(4):1457-1465. doi: 10.1007/s12253-018-0500-y. Epub 2018 Oct 27.

Abstract

Epigenetic aberrations are well known to play an important role in carcinogenesis, and also have a great potential to serve as biomarkers in many types of cancers, including ovarian cancer in which sensitive and specific biomarkers and detection methods are critically needed. The aim of this study was to investigate methylation of cadherin genes CDH10, CDH13 and CDH18 in ovarian cancer tissue by comparison with control tissue. The study group consisted of 38 patients with ovarian cancer and 25 control patients. For detection of epigenetic events we used next generation sequencing, the most important data were confirmed using high-resolution melting analysis and real-time PCR. We observed significantly higher methylation in CDH13, sporadic methylation in CDH10 and loss of methylation in CDH18 in the ovarian cancer group compared with the control group. These observations suggest that changes in methylation of cadherin genes may be one of the major mechanisms associated with ovarian cancer progression. In addition, because of the high frequency of methylation of the CDH13 gene in the early stages of ovarian cancer, the analyzed CpG sites might be good targets for next study of potential ovarian cancer screening biomarkers.

Keywords: Cadherins; Epigenetics; Methylation; Next generation sequencing; Ovarian cancer.

MeSH terms

  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Cadherins / genetics*
  • Case-Control Studies
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / pathology
  • DNA Methylation*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Promoter Regions, Genetic
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Cadherins
  • H-cadherin