{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:04:23Z","timestamp":1776931463531,"version":"3.51.2"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100017050","name":"Cycle for Survival","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100017050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017050","name":"Cycle for Survival","doi-asserted-by":"publisher","award":["P50 CA217694"],"award-info":[{"award-number":["P50 CA217694"]}],"id":[{"id":"10.13039\/100017050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>CREB<\/jats:italic> gene family (<jats:italic>ATF1<\/jats:italic>, <jats:italic>CREB1<\/jats:italic>, <jats:italic>CREM<\/jats:italic>) fusions with either <jats:italic>EWSR1<\/jats:italic> or <jats:italic>FUS<\/jats:italic> gene partners drive the pathogenesis of a wide range of neoplasms, including various soft tissue tumors, intracranial myxoid mesenchymal tumors (IMMTs), hyalinizing clear cell carcinoma (HCCC), and rare mesotheliomas. Recently, a <jats:italic>SMARCA2<\/jats:italic>::<jats:italic>CREM<\/jats:italic> fusion was reported in one case each of IMMT and HCCC. In this study, we expand the clinicopathologic and molecular spectrum of these neoplasms by describing three additional cases with <jats:italic>SMARCA2<\/jats:italic>::<jats:italic>CREM<\/jats:italic> and one with a novel <jats:italic>SMARCA4<\/jats:italic>::<jats:italic>CREM<\/jats:italic> fusion, highlighting the recurrent potential of additional CREB gene fusion partners beyond FET family members. To evaluate if these fusions define a new pathologic entity, we performed a comprehensive genomic and methylation analysis and compared the results to other related tumors. Tumors occurred in children and young adults (median age 20\u2009years) and spanned a broad anatomic distribution, including soft tissue, intracranial, head and neck, and prostatic urethra. Microscopically, the tumors shared an undifferentiated round to epithelioid cell phenotype and a hyalinized fibrous stroma. Immunohistochemically, a polyphenotypic profile was observed, with variable expression of SOX10, desmin, and\/or epithelial markers. No targetable genomic alterations were found using panel\u2010based DNA sequencing. By DNA methylation and transcriptomic analyses, tumors grouped closely to <jats:italic>FET<\/jats:italic>::<jats:italic>CREB<\/jats:italic> entities, but not with <jats:italic>SMARCA4<\/jats:italic>\/<jats:italic>SMARCB1<\/jats:italic>\u2010deficient tumors. High expression of CREM by immunohistochemistry was also documented in these tumors. Patients experienced local recurrence (<jats:italic>n<\/jats:italic>\u2009=\u20092), locoregional lymph node metastases (<jats:italic>n<\/jats:italic>\u2009=\u20092), and an isolated visceral metastasis (<jats:italic>n<\/jats:italic>\u2009=\u20091). Overall, our study suggests that <jats:italic>SMARCA2\/4<\/jats:italic>::<jats:italic>CREM<\/jats:italic> fusions define a distinct group of neoplasms with round cell to epithelioid histology, a variable immunoprofile, and a definite risk of malignancy. Larger studies are needed to further explore the pathogenetic relationship with the <jats:italic>FET<\/jats:italic>::<jats:italic>CREB<\/jats:italic> family of tumors. \u00a9 2024 The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6350","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T04:00:46Z","timestamp":1727668846000},"page":"305-317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Expanding the clinicopathologic spectrum and genomic landscape of tumors with <scp><i>SMARCA2<\/i><\/scp><i>\/4<\/i>::<scp><i>CREM<\/i><\/scp> fusions"],"prefix":"10.1002","volume":"264","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0216-5330","authenticated-orcid":false,"given":"Joanna","family":"Cyrta","sequence":"first","affiliation":[{"name":"Department of Pathology, Institut Curie PSL Research University  Paris 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