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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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.
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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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