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The Role of Aberrant DNA Methylation in Misregulation of Gene Expression in Gonadotroph Nonfunctioning Pituitary Tumors
Gonadotroph nonfunctioning pituitary adenomas (NFPAs) are common intracranial tumors, but the role of aberrant epigenetic regulation in their development remains poorly understood. In this study, we investigated the effect of impaired CpG methylation in NFPAs. We determined DNA methylation and trans...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895980/ https://www.ncbi.nlm.nih.gov/pubmed/31731486 http://dx.doi.org/10.3390/cancers11111650 |
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author | Kober, Paulina Boresowicz, Joanna Rusetska, Natalia Maksymowicz, Maria Paziewska, Agnieszka Dąbrowska, Michalina Kunicki, Jacek Bonicki, Wiesław Ostrowski, Jerzy Siedlecki, Janusz A. Bujko, Mateusz |
author_facet | Kober, Paulina Boresowicz, Joanna Rusetska, Natalia Maksymowicz, Maria Paziewska, Agnieszka Dąbrowska, Michalina Kunicki, Jacek Bonicki, Wiesław Ostrowski, Jerzy Siedlecki, Janusz A. Bujko, Mateusz |
author_sort | Kober, Paulina |
collection | PubMed |
description | Gonadotroph nonfunctioning pituitary adenomas (NFPAs) are common intracranial tumors, but the role of aberrant epigenetic regulation in their development remains poorly understood. In this study, we investigated the effect of impaired CpG methylation in NFPAs. We determined DNA methylation and transcriptomic profiles in 32 NFPAs and normal pituitary sections using methylation arrays and sequencing, respectively. Ten percent of differentially methylated CpGs were correlated with gene expression, and the affected genes are involved in a variety of tumorigenesis-related pathways. Different proportions of gene body and promoter region localization were observed in CpGs with negative and positive correlations between methylation and gene expression, and different proportions of CpGs were located in ‘open sea’ and ‘shelf/shore’ regions. The expression of ~8% of genes differentially expressed in NFPAs was related to aberrant methylation. Methylation levels of seven CpGs located in the regulatory regions of FAM163A, HIF3A and PRSS8 were determined by pyrosequencing, and gene expression was measured by qRT-PCR and immunohistochemistry in 83 independent NFPAs. The results clearly confirmed the negative correlation between methylation and gene expression for these genes. By identifying which aberrantly methylated CpGs affect gene expression in gonadotrophinomas, our data confirm the role of aberrant methylation in pathogenesis of gonadotroph NFPAs. |
format | Online Article Text |
id | pubmed-6895980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68959802019-12-24 The Role of Aberrant DNA Methylation in Misregulation of Gene Expression in Gonadotroph Nonfunctioning Pituitary Tumors Kober, Paulina Boresowicz, Joanna Rusetska, Natalia Maksymowicz, Maria Paziewska, Agnieszka Dąbrowska, Michalina Kunicki, Jacek Bonicki, Wiesław Ostrowski, Jerzy Siedlecki, Janusz A. Bujko, Mateusz Cancers (Basel) Article Gonadotroph nonfunctioning pituitary adenomas (NFPAs) are common intracranial tumors, but the role of aberrant epigenetic regulation in their development remains poorly understood. In this study, we investigated the effect of impaired CpG methylation in NFPAs. We determined DNA methylation and transcriptomic profiles in 32 NFPAs and normal pituitary sections using methylation arrays and sequencing, respectively. Ten percent of differentially methylated CpGs were correlated with gene expression, and the affected genes are involved in a variety of tumorigenesis-related pathways. Different proportions of gene body and promoter region localization were observed in CpGs with negative and positive correlations between methylation and gene expression, and different proportions of CpGs were located in ‘open sea’ and ‘shelf/shore’ regions. The expression of ~8% of genes differentially expressed in NFPAs was related to aberrant methylation. Methylation levels of seven CpGs located in the regulatory regions of FAM163A, HIF3A and PRSS8 were determined by pyrosequencing, and gene expression was measured by qRT-PCR and immunohistochemistry in 83 independent NFPAs. The results clearly confirmed the negative correlation between methylation and gene expression for these genes. By identifying which aberrantly methylated CpGs affect gene expression in gonadotrophinomas, our data confirm the role of aberrant methylation in pathogenesis of gonadotroph NFPAs. MDPI 2019-10-25 /pmc/articles/PMC6895980/ /pubmed/31731486 http://dx.doi.org/10.3390/cancers11111650 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kober, Paulina Boresowicz, Joanna Rusetska, Natalia Maksymowicz, Maria Paziewska, Agnieszka Dąbrowska, Michalina Kunicki, Jacek Bonicki, Wiesław Ostrowski, Jerzy Siedlecki, Janusz A. Bujko, Mateusz The Role of Aberrant DNA Methylation in Misregulation of Gene Expression in Gonadotroph Nonfunctioning Pituitary Tumors |
title | The Role of Aberrant DNA Methylation in Misregulation of Gene Expression in Gonadotroph Nonfunctioning Pituitary Tumors |
title_full | The Role of Aberrant DNA Methylation in Misregulation of Gene Expression in Gonadotroph Nonfunctioning Pituitary Tumors |
title_fullStr | The Role of Aberrant DNA Methylation in Misregulation of Gene Expression in Gonadotroph Nonfunctioning Pituitary Tumors |
title_full_unstemmed | The Role of Aberrant DNA Methylation in Misregulation of Gene Expression in Gonadotroph Nonfunctioning Pituitary Tumors |
title_short | The Role of Aberrant DNA Methylation in Misregulation of Gene Expression in Gonadotroph Nonfunctioning Pituitary Tumors |
title_sort | role of aberrant dna methylation in misregulation of gene expression in gonadotroph nonfunctioning pituitary tumors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895980/ https://www.ncbi.nlm.nih.gov/pubmed/31731486 http://dx.doi.org/10.3390/cancers11111650 |
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