{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T06:40:05Z","timestamp":1756449605911,"version":"3.44.0"},"reference-count":23,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Mastermind\u2010like transcriptional coactivator (<jats:italic>MAML<\/jats:italic>) gene fusions have been documented in Thymic Epithelial Tumors (TETs). Specifically, lysine methyltransferase 2A (<jats:italic>KMT2A)::MAML2<\/jats:italic> gene fusions are associated with type B2 and B3 thymomas. Here, we report for the first time a young patient with invasive type B3 thymoma harboring a novel <jats:italic>KMT2A::MAML3<\/jats:italic> gene fusion. <jats:italic>MAML3<\/jats:italic> and <jats:italic>MAML2<\/jats:italic> are paralogues. In addition to the classic type B3 thymoma histology, this article documents intratumor heterogeneity, characterized by a trabecular and fascicular pattern, as well as areas of clear cells. Immunohistochemistry showed keratin positivity in tumor cells, while neuroendocrine markers were negative in trabecular regions. DNA\u2010based next\u2010generation sequencing failed to identify pathogenic variants, but RNA sequencing detected the <jats:italic>KMT2A::MAML3<\/jats:italic> gene fusion. We compared the gene fusion sites of <jats:italic>MAML2<\/jats:italic> and <jats:italic>MAML3<\/jats:italic>, focusing on exon 2, and found that they share similar functional protein domains. Moreover, the same domain appeared downstream of the <jats:italic>KMT2A::MAML2<\/jats:italic> fusion protein. Therefore, we hypothesize that <jats:italic>MAML3<\/jats:italic> gene fusions, like <jats:italic>MAML2<\/jats:italic>, lead to abnormal Notch signaling pathways and increase the invasive potential of certain thymoma subtypes. Our findings expand the genetic landscape of aggressive thymomas and offer new insights for molecular studies in TETs.<\/jats:p>","DOI":"10.1002\/gcc.70071","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T06:36:27Z","timestamp":1754980587000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Type <scp>B3<\/scp> Thymoma With a Novel <i>KMT2A::MAML3<\/i> Fusion: Expanding the Spectrum of Gene Fusions Beyond the <scp><i>MAML2<\/i><\/scp> Gene"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8063-1512","authenticated-orcid":false,"given":"Ziqi","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pathology Nanfang Hospital, School of Basic Medical Sciences, Southern Medical University  Guangzhou Guangdong China"},{"name":"Guangdong Province Key Laboratory of Molecular Tumor Pathology  Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqi","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology Nanfang Hospital, School of Basic Medical Sciences, Southern Medical University  Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conghao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology Nanfang Hospital, School of Basic Medical Sciences, Southern Medical University  Guangzhou Guangdong China"},{"name":"Guangdong Province Key Laboratory of Molecular Tumor Pathology  Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5952-2319","authenticated-orcid":false,"given":"Jie","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology Nanfang Hospital, School of Basic Medical Sciences, Southern Medical University  Guangzhou Guangdong 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