Open Access Research article

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

Hitoshi Hiura1, Hiroaki Okae1, Hisato Kobayash2, Naoko Miyauchi1, Fumi Sato1, Akiko Sato3, Fumihiko Suzuki3, Satoru Nagase3, Junichi Sugawara3, Kunihiko Nakai4, Nobuo Yaegashi3 and Takahiro Arima1*

Author Affiliations

1 Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan

2 Department of BioScience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan

3 Departments of Obstetrics and Gynecology, Tohoku University Graduate, School of Medicine, Sendai, Japan

4 Department of Development and Environmental Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

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BMC Medical Genomics 2012, 5:8  doi:10.1186/1755-8794-5-8

Published: 26 March 2012

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.

Keywords:
Genomic imprinting; Ovarian cancer; DNA methylation; Bisulphite PCR-Luminex(BPL)method; LOI (loss of imprinting)