Next Article in Journal
Pro-Resolving Molecules—New Approaches to Treat Sepsis?
Previous Article in Journal
Gomisin N Inhibits Melanogenesis through Regulating the PI3K/Akt and MAPK/ERK Signaling Pathways in Melanocytes
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(2), 474; doi:10.3390/ijms18020474

Next-Generation Sequencing Approach in Methylation Analysis of HNF1B and GATA4 Genes: Searching for Biomarkers in Ovarian Cancer

1
Institute of Clinical Biochemistry and Diagnostics, Charles University Faculty of Medicine and University Hospital Hradec Kralove, 500 05 Hradec Kralove, Czech Republic
2
The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital Hradec Kralove, 500 05 Hradec Kralove, Czech Republic
3
Department of Clinical Genetics, University Hospital Hradec Kralove, 500 05 Hradec Kralove, Czech Republic
4
Department of Obstetrics and Gynecology, Charles University Faculty of Medicine and University Hospital Hradec Kralove, 500 05 Hradec Kralove, Czech Republic
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 3 February 2017 / Revised: 14 February 2017 / Accepted: 16 February 2017 / Published: 22 February 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [2595 KB, uploaded 22 February 2017]   |  

Abstract

DNA methylation is well-known to be associated with ovarian cancer (OC) and has great potential to serve as a biomarker in monitoring response to therapy and for disease screening. The purpose of this study was to investigate methylation of HNF1B and GATA4 and correlate detected methylation with clinicopathological characteristic of OC patients. The study group consisted of 64 patients with OC and 35 control patients. To determine the most important sites of HNF1B and GATA4, we used next-generation sequencing. For further confirmation of detected methylation of selected regions, we used high-resolution melting analysis and methylation-specific real-time polymerase chain reaction (PCR). Selected regions of HNF1B and GATA4 were completely methylation free in all control samples, whereas methylation-positive pattern was observed in 32.8% (HNF1B) and 45.3% (GATA4) of OC samples. Evaluating both genes together, we were able to detect methylation in 65.6% of OC patients. We observed a statistically significant difference in HNF1B methylation between samples with different stages of OC. We also detected subtype specific methylation in GATA4 and a decrease of methylation in late stages of OC. The combination of unmethylated HNF1B and methylated GATA4 was associated with longer overall survival. In our study, we employed innovative approach of methylation analysis of HNF1B and GATA4 to search for possible epigenetic biomarkers. We confirmed the significance of the HNF1B and GATA4 hypermethylation with emphasis on the need of selecting the most relevant sites for analysis. We suggest selected CpGs to be further examined as a potential positive prognostic factor. View Full-Text
Keywords: ovarian cancer; methylation; GATA4; HNF1B; next-generation sequencing; biomarker ovarian cancer; methylation; GATA4; HNF1B; next-generation sequencing; biomarker
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Bubancova, I.; Kovarikova, H.; Laco, J.; Ruszova, E.; Dvorak, O.; Palicka, V.; Chmelarova, M. Next-Generation Sequencing Approach in Methylation Analysis of HNF1B and GATA4 Genes: Searching for Biomarkers in Ovarian Cancer. Int. J. Mol. Sci. 2017, 18, 474.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top