High-throughput detection of aberrant imprint methylation in the ovarian cancer by the bisulphite PCR-Luminex method

BMC Med Genomics. 2012 Mar 26:5:8. doi: 10.1186/1755-8794-5-8.

Abstract

Background: Aberrant DNA methylation leads to loss of heterozygosity (LOH) or loss of imprinting (LOI) as the first hit during human carcinogenesis. Recently we developed a new high-throughput, high-resolution DNA methylation analysis method, bisulphite PCR-Luminex (BPL), using sperm DNA and demonstrated the effectiveness of this novel approach in rapidly identifying methylation errors.

Results: In the current study, we applied the BPL method to the analysis of DNA methylation for identification of prognostic panels of DNA methylation cancer biomarkers of imprinted genes. We found that the BPL method precisely quantified the methylation status of specific DNA regions in somatic cells. We found a higher frequency of LOI than LOH. LOI at IGF2, PEG1 and H19 were frequent alterations, with a tendency to show a more hypermethylated state. We detected changes in DNA methylation as an early event in ovarian cancer. The degree of LOI (LOH) was associated with altered DNA methylation at IGF2/H19 and PEG1.

Conclusions: The relative ease of BPL method provides a practical method for use within a clinical setting. We suggest that DNA methylation of H19 and PEG1 differentially methylated regions (DMRs) may provide novel biomarkers useful for screening, diagnosis and, potentially, for improving the clinical management of women with human ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • DNA Methylation*
  • Female
  • High-Throughput Screening Assays*
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Loss of Heterozygosity
  • Luminescent Measurements*
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Polymerase Chain Reaction
  • Proteins / genetics
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics
  • Sulfites / chemistry

Substances

  • Biomarkers, Tumor
  • H19 long non-coding RNA
  • IGF2 protein, human
  • Proteins
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Sulfites
  • mesoderm specific transcript protein
  • Insulin-Like Growth Factor II
  • hydrogen sulfite