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Methylome Analysis in Nonfunctioning and GH-Secreting Pituitary Adenomas
Pituitary adenomas (PAs), usually benign lesions, can sometimes present with “aggressive” features (rapid growth, local invasiveness, scarce response to conventional treatments). Despite the fact that a few genetic alterations have been associated to this clinical behavior, the role of epigenetic mo...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007725/ https://www.ncbi.nlm.nih.gov/pubmed/35432200 http://dx.doi.org/10.3389/fendo.2022.841118 |
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author | Giuffrida, Giuseppe D’Argenio, Valeria Ferraù, Francesco Lasorsa, Vito Alessandro Polito, Francesca Aliquò, Federica Ragonese, Marta Cotta, Oana Ruxandra Alessi, Ylenia Oteri, Rosaria Di Maggio, Federica Asmundo, Alessio Romeo, Petronilla Daniela Spagnolo, Federica Pastore, Lucio Angileri, Filippo Flavio Capasso, Mario Cannavò, Salvatore Aguennouz, M’Hammed |
author_facet | Giuffrida, Giuseppe D’Argenio, Valeria Ferraù, Francesco Lasorsa, Vito Alessandro Polito, Francesca Aliquò, Federica Ragonese, Marta Cotta, Oana Ruxandra Alessi, Ylenia Oteri, Rosaria Di Maggio, Federica Asmundo, Alessio Romeo, Petronilla Daniela Spagnolo, Federica Pastore, Lucio Angileri, Filippo Flavio Capasso, Mario Cannavò, Salvatore Aguennouz, M’Hammed |
author_sort | Giuffrida, Giuseppe |
collection | PubMed |
description | Pituitary adenomas (PAs), usually benign lesions, can sometimes present with “aggressive” features (rapid growth, local invasiveness, scarce response to conventional treatments). Despite the fact that a few genetic alterations have been associated to this clinical behavior, the role of epigenetic modifications, mainly methylation and miRNAs activity, is now opening new frontiers in this field. We evaluated the methylation profile of 21 PA (11 GH-omas, 10 nonfunctioning tumors—NFPAs) samples from TNS surgery and 5 normal pituitaries, collected at our neurosurgery between 2015 and 2017. DNA was extracted and sequenced, selecting 184,841 target regions. Moreover, methylation profiles were correlated with demographic, radiological, and clinicopathological features. NFPAs showed higher methylation levels vs. GH-omas, with 178 differentially methylated regions (DMRs) mainly consisting of noncoding and intronic sequences, and mostly localized in the open sea regions. We also found three hypermethylated genes (C7orf50, GNG7, and BAHCC1) involved in tumorigenesis processes and potentially influencing pituitary tumor pathophysiology. Among the clinicopathological features, only the maximum diameter resulted significantly higher in NFPAs. Our data provide further evidence of the complex epigenetic background of pituitary tumors. In line with the current literature, we confirmed a significant prevalence of hypermethylation in NFPAs vs. GH-omas, whose pathophysiological consequence is yet to be defined. |
format | Online Article Text |
id | pubmed-9007725 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90077252022-04-15 Methylome Analysis in Nonfunctioning and GH-Secreting Pituitary Adenomas Giuffrida, Giuseppe D’Argenio, Valeria Ferraù, Francesco Lasorsa, Vito Alessandro Polito, Francesca Aliquò, Federica Ragonese, Marta Cotta, Oana Ruxandra Alessi, Ylenia Oteri, Rosaria Di Maggio, Federica Asmundo, Alessio Romeo, Petronilla Daniela Spagnolo, Federica Pastore, Lucio Angileri, Filippo Flavio Capasso, Mario Cannavò, Salvatore Aguennouz, M’Hammed Front Endocrinol (Lausanne) Endocrinology Pituitary adenomas (PAs), usually benign lesions, can sometimes present with “aggressive” features (rapid growth, local invasiveness, scarce response to conventional treatments). Despite the fact that a few genetic alterations have been associated to this clinical behavior, the role of epigenetic modifications, mainly methylation and miRNAs activity, is now opening new frontiers in this field. We evaluated the methylation profile of 21 PA (11 GH-omas, 10 nonfunctioning tumors—NFPAs) samples from TNS surgery and 5 normal pituitaries, collected at our neurosurgery between 2015 and 2017. DNA was extracted and sequenced, selecting 184,841 target regions. Moreover, methylation profiles were correlated with demographic, radiological, and clinicopathological features. NFPAs showed higher methylation levels vs. GH-omas, with 178 differentially methylated regions (DMRs) mainly consisting of noncoding and intronic sequences, and mostly localized in the open sea regions. We also found three hypermethylated genes (C7orf50, GNG7, and BAHCC1) involved in tumorigenesis processes and potentially influencing pituitary tumor pathophysiology. Among the clinicopathological features, only the maximum diameter resulted significantly higher in NFPAs. Our data provide further evidence of the complex epigenetic background of pituitary tumors. In line with the current literature, we confirmed a significant prevalence of hypermethylation in NFPAs vs. GH-omas, whose pathophysiological consequence is yet to be defined. Frontiers Media S.A. 2022-03-30 /pmc/articles/PMC9007725/ /pubmed/35432200 http://dx.doi.org/10.3389/fendo.2022.841118 Text en Copyright © 2022 Giuffrida, D’Argenio, Ferraù, Lasorsa, Polito, Aliquò, Ragonese, Cotta, Alessi, Oteri, Di Maggio, Asmundo, Romeo, Spagnolo, Pastore, Angileri, Capasso, Cannavò and Aguennouz https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Giuffrida, Giuseppe D’Argenio, Valeria Ferraù, Francesco Lasorsa, Vito Alessandro Polito, Francesca Aliquò, Federica Ragonese, Marta Cotta, Oana Ruxandra Alessi, Ylenia Oteri, Rosaria Di Maggio, Federica Asmundo, Alessio Romeo, Petronilla Daniela Spagnolo, Federica Pastore, Lucio Angileri, Filippo Flavio Capasso, Mario Cannavò, Salvatore Aguennouz, M’Hammed Methylome Analysis in Nonfunctioning and GH-Secreting Pituitary Adenomas |
title | Methylome Analysis in Nonfunctioning and GH-Secreting Pituitary Adenomas |
title_full | Methylome Analysis in Nonfunctioning and GH-Secreting Pituitary Adenomas |
title_fullStr | Methylome Analysis in Nonfunctioning and GH-Secreting Pituitary Adenomas |
title_full_unstemmed | Methylome Analysis in Nonfunctioning and GH-Secreting Pituitary Adenomas |
title_short | Methylome Analysis in Nonfunctioning and GH-Secreting Pituitary Adenomas |
title_sort | methylome analysis in nonfunctioning and gh-secreting pituitary adenomas |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007725/ https://www.ncbi.nlm.nih.gov/pubmed/35432200 http://dx.doi.org/10.3389/fendo.2022.841118 |
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