{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:55:41Z","timestamp":1788306941066,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T00:00:00Z","timestamp":1665100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To profile clinically non\u2010aggressive and aggressive pituitary adenomas (PAs)\/pituitary neuroendocrine tumours (PitNETs) and pituitary carcinomas for somatic mutations and epigenetic alterations of genes involved in cell proliferation\/differentiation, microRNAs (miRNA)\/long noncoding RNA (LncRNA)\u2010post\u2010transcriptional regulators and therapy targets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Retrospective observational study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Measurements<\/jats:title><jats:p>A total of 64 non\u2010aggressive and 41 aggressive PAs\/PitNETs and 6 pituitary carcinomas treated by endoscopic surgery with \u22651\u2010year follow\u2010up were included. Somatic mutations of 17 genes and DNA methylation of 22 genes were assessed. Ten normal pituitaries were used as control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found at least one mutation in 17 tumours, including 6\/64 non\u2010aggressive, 10\/41 aggressive PAs\/PitNETs, and 1\/6 pituitary carcinoma. <jats:italic>AIP<\/jats:italic> (<jats:italic>N<\/jats:italic>\u2009=\u20096) was the most frequently mutated gene, followed by <jats:italic>NOTCH<\/jats:italic> (4), and <jats:italic>TP53<\/jats:italic> (3). Hypermethylation of <jats:italic>PARP15, LINC00599, ZAP70<\/jats:italic> was more common in aggressive than non\u2010aggressive PAs\/PITNETs (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). Lower levels of methylation of <jats:italic>AIP, GNAS<\/jats:italic> and <jats:italic>PDCD1<\/jats:italic> were detected in aggressive PAs\/PITNETs than non\u2010aggressive ones (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). For X\u2010linked genes, males presented higher level of methylation of <jats:italic>FLNA, UXT<\/jats:italic> and <jats:italic>MAGE<\/jats:italic> family (<jats:italic>MAGEA11, MAGEA1, MAGEC2<\/jats:italic>) genes in aggressive vs. non\u2010aggressive PAs\/PITNETs (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05).<\/jats:p><jats:p>In pituitary carcinomas, methylation of autosomal genes <jats:italic>PARP15, LINC00599, MIR193<\/jats:italic> and <jats:italic>ZAP70<\/jats:italic> was higher than in PAs\/PITNETs, while X\u2010linked genes methylation level was lower.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Somatic mutations and methylation levels of genes involved in cell proliferation\/differentiation, miRNA\/LncRNA\u2010post\u2010transcriptional regulators and targets of antineoplastic therapies are different in non\u2010aggressive and in aggressive PAs\/PitNETs. Methylation profile also varies according to gender. Combined genetic\u2010epigenetic analysis, in association with clinico\u2010radiological\u2010pathological data, may be of help in predicting PA\/PitNET behaviour.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14827","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T10:21:26Z","timestamp":1664187686000},"page":"763-772","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Epigenomic and somatic mutations of pituitary tumors with clinical and pathological correlations in 111 patients"],"prefix":"10.1111","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8416-1669","authenticated-orcid":false,"given":"Federica","family":"Guaraldi","sequence":"first","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna Bologna 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