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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...

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Autores principales: Kober, Paulina, Boresowicz, Joanna, Rusetska, Natalia, Maksymowicz, Maria, Paziewska, Agnieszka, Dąbrowska, Michalina, Kunicki, Jacek, Bonicki, Wiesław, Ostrowski, Jerzy, Siedlecki, Janusz A., Bujko, Mateusz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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