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Although the interest in TME in somatotropinomas has increased exponentially over the last few decades, there is limited elucidation of its mechanisms, particularly in relation to genes expression involved in its regulation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A retrospective, observational, single-center study was conducted on 85 subjects: 46 patients diagnosed with acromegaly and 39 controls. After DNA extraction, clinical exome sequencing was performed and genomic alterations were detected, classified, and filtered using a dedicated bioinformatics pipeline.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>5759 unique genetic variants were found in patients with acromegaly. 33 patients (72%) showed the presence of at least one pathogenic variant in at least one of the following genes: FANCD2, SPTA1, TYRO3, and ZNF335. The enrichment pathway analysis of mutated genes was performed and showed that these genes were included in the same genetic pathway called \u201cregulation of lymphocyte activation\u201d (GO:0051249). Inflammatory infiltrate was analyzed in histological samples in 26 patients. A significantly higher number of CD68\u2009+\u2009macrophages (P-value\u2009=\u20090.008), a lower number of CD8\u2009+\u2009T lymphocytes (P-value\u2009=\u20090.037) and a higher CD68\u2009+\u2009macrophages\/ CD8\u2009+\u2009T-lymphocytes ratio (P-value\u2009=\u20090.004) were observed in patients with pathogenic variants of genes of \u201cregulation of lymphocyte activation\u201d pathway.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This study provides new insights into the genetic basis of the TME in somatotropinomas and suggests that genetics may influence immune cells infiltration in acromegaly.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11102-025-01537-w","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T22:27:13Z","timestamp":1748212033000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genes of the \u201cregulation of lymphocyte activation\u201d pathway may influence immune cells infiltration in growth hormone secreting pituitary tumors"],"prefix":"10.1007","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9241-2392","authenticated-orcid":false,"given":"Sabrina","family":"Chiloiro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia","family":"Costanza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni Luca","family":"Scaglione","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo","family":"Russo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmela","family":"Nardelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Giampietro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Paolo","family":"Mattogno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liverana","family":"Lauretti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Rindi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"De Marinis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Gessi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Doglietto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ettore Domenico","family":"Capoluongo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Pontecorvi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"1537_CR1","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/s11060-013-1354-5","volume":"117","author":"ED Aflorei","year":"2014","unstructured":"Aflorei ED, Korbonits M (2014) Epidemiology and etiopathogenesis of pituitary adenomas. 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