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 TITLE=Methylome Analysis in Nonfunctioning and GH-Secreting Pituitary Adenomas JOURNAL=Frontiers in Endocrinology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.841118 DOI=10.3389/fendo.2022.841118 ISSN=1664-2392 ABSTRACT=

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.