{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:11:47Z","timestamp":1792498307292,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009888","name":"Regione Toscana","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The molecular landscape of thymic epithelial tumors has been partially elucidated. GTF2I mutation drives the pathogenesis in approximately 50% of tumors; however, the key molecular aberrations in the other cases remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We designed a panel including the most frequently mutated genes in thymic epithelial tumors and sequenced tumor and normal DNA from 70 patients prospectively accrued at a single institution in the Thymogene trial. Moreover, 19 neoplastic samples were dissociated to isolate tumor cells using flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GTF2I mutations were the most common, being present in 41% of patients. GTF2I mutations were prevalent in type A and AB thymomas, in Stage I\u2013II tumors, and in patients without myasthenia gravis. The unique pattern of mutually exclusive and co\u2010occurring mutations suggests a distinct pathogenesis for thymomas with and without GTF2I mutation. In 39% of patients, no mutations were found in the 77 genes evaluated. The absence of epithelial cells in some dissociated tumors highlights the challenge of identifying mutations in a subset of thymic epithelial tumors that lack the GTF2I mutation. Mutational signatures, including COSMIC 1, 19, and 25, were enriched, possibly linked to 5\u2032\u2010methylcytosine deamination and the effects of chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GTF2I mutations drive the growth of a significant portion of thymic epithelial tumors, often in conjunction with other gene mutations. Somatic mutations are not commonly found in many GTF2I wild\u2010type tumors, where the underlying genomic abnormalities remain elusive, even when using a dedicated tool for sequencing thymic epithelial tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1759-7714.70205","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T12:55:57Z","timestamp":1765976157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Somatic Mutations of Thymic Epithelial Tumors Identified in the Prospective\n                    <scp>THYMOGENE<\/scp>\n                    Trial"],"prefix":"10.1111","volume":"16","author":[{"given":"Eleonora","family":"Pardini","sequence":"first","affiliation":[{"name":"Department of Translational Research and New Surgical and Medical Technologies University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Cucchiara","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Barachini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Montali","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisella","family":"Sardo Infirri","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Surgical and Medical Technologies University of Pisa  Pisa 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Hospital of Pisa  Pisa Italy"},{"name":"Thoracic Surgery, Department of Surgical, Medical and Molecular Pathology and Critical Care University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Nicol\u00ec","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Translational Research and New Surgical and Medical Technologies University of Pisa  Pisa Italy"},{"name":"Department of Biomedicine and Prevention The University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Copped\u00e8","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Translational Research and New Surgical and Medical Technologies University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Bacchin","sequence":"additional","affiliation":[{"name":"Thoracic Surgery, Department of Surgical, Medical and Molecular Pathology and Critical Care University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelina Cristina","family":"Zafira","sequence":"additional","affiliation":[{"name":"Robotic surgery, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Aprile","sequence":"additional","affiliation":[{"name":"Thoracic Surgery, Department of Surgical, Medical and Molecular Pathology and Critical Care University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Melfi","sequence":"additional","affiliation":[{"name":"Robotic surgery, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine University of Pisa  Pisa 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