Association of Aberrant Methylation at Promoter Regions of Tumor Suppressor Genes with Placental Pathologies

Abstract

Aim: The resemblance between invasive behavior of cancer cells and placental trophoblasts and the role of aberrant epigenetic regulation in cancer development is well known. Methods: We analyzed the role of promoter region CpG-methylation and H3K9/27me3 of tumor suppressor genes in normal and pathological pregnancies and utilized their CpG-methylation data to search for fetal DNA epigenetic marker in maternal blood. Results: CpG and H3K9/27-methylation associated decreased expression of RASSF1A and APC and increased expression of P16, RB1 and PRKCDBP was observed with advancing normal gestation. Gestational trophoblastic diseases and preeclampsia revealed gene-specific epigenetic deregulation of candidate tumor suppressor genes. Furthermore, APC and PRKCDBP showed the potential to act as fetal DNA epigenetic markers, similar to RASSF1A. Conclusion: Deregulation of methylation of tumor suppressor genes contributes to the development of preeclampsia and gestational trophoblastic diseases. APC and PRKCDBP may act as fetal DNA epigenetic markers for prenatal diagnosis.

Keywords::

• APC
• DNA methylation
• GTDs
• histone modifications
• P16
• PE
• placenta
• PRKCDBP
• RASSF1A
• RB1

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi.16.7

Author contributions

The authors were responsible for the following aspects of the study. B Rahat performed and analyzed MS-HRM, qPCR, ChIP assay and cell culturing assays. J Kaur and B Rahat planned this study and were involved also involved in the interpretation of data. S Thakur and A Hamid analyzed methylation data. R Bagga played role in clinical data collection and patient recruitment. B Rahat and J Kaur prepared the manuscript while all authors critically revised and approved the manuscript.

Financial & competing interests disclosure

This work was supported by Indian Council of Medical Education and Research (ICMR 5/10/FR/3/2010-RHN). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval for all human experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by Indian Council of Medical Education and Research (ICMR 5/10/FR/3/2010-RHN). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.