{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:17:56Z","timestamp":1790792276857,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T00:00:00Z","timestamp":1559260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["16cm0106520h0001"],"award-info":[{"award-number":["16cm0106520h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["15cm0106141h0002"],"award-info":[{"award-number":["15cm0106141h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,12,15]]},"abstract":"<jats:p>Tenosynovial giant cell tumor (TSGCT) is a rare neoplasm. Although surgical resection is the widely accepted primary treatment for TSGCT, recurrences are frequent, and patients\u2019 joint function may be severely compromised. Previous studies reported that <jats:italic>CSF1\u2010COL6A3<\/jats:italic> fusion genes were identified in approximately 30% of TSGCTs. The aim of our study was to comprehensively clarify the genomic abnormalities in TSGCTs. We performed whole exome sequencing in combination with target sequence validation on 34 TSGCT samples. RNA sequencing was also performed on 18 samples. RNA sequencing revealed fusion transcripts involving <jats:italic>CSF1<\/jats:italic>, including novel <jats:italic>CSF1<\/jats:italic>\u2010<jats:italic>VCAM1<\/jats:italic>, <jats:italic>CSF1<\/jats:italic>\u2010<jats:italic>FN1<\/jats:italic> and <jats:italic>CSF1<\/jats:italic>\u2010<jats:italic>CDH1<\/jats:italic> fusions, in 13\/18 (72%) cases. These fusion genes were validated by chromogenic <jats:italic>in situ<\/jats:italic> hybridization. All <jats:italic>CSF1<\/jats:italic> fusions resulted in the deletion of <jats:italic>CSF1<\/jats:italic> exon 9, which was previously shown to be an important negative regulator of CSF1 expression. We also found that 12 (35%) of the 34 TSGCT samples harbored <jats:italic>CBL<\/jats:italic> missense mutations. All mutations were detected in exons 8 or 9, which encode the linker and RING finger domain. Among these mutations, C404Y, L380P and R420Q were recurrent. <jats:italic>CBL<\/jats:italic>\u2010mutated cases showed higher JAK2 expression than wild\u2010type <jats:italic>CBL<\/jats:italic> cases (<jats:italic>p<\/jats:italic> = 0.013). <jats:italic>CSF1<\/jats:italic> fusion genes and <jats:italic>CBL<\/jats:italic> mutations were not mutually exclusive, and both alterations were detected in six of the 18 (33%) tumors. The frequent deletion of <jats:italic>CSF1<\/jats:italic> exon 9 in the fusion transcripts suggested the importance of this event in the etiology of TSGCT. Our results may contribute to the development of new targeted therapies using JAK2 inhibitors for <jats:italic>CBL<\/jats:italic>\u2010mutated TSGCT.<\/jats:p>","DOI":"10.1002\/ijc.32421","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T14:56:51Z","timestamp":1558364211000},"page":"3276-3284","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Massively parallel sequencing of tenosynovial giant cell tumors reveals novel CSF1 fusion transcripts and novel somatic CBL mutations"],"prefix":"10.1002","volume":"145","author":[{"given":"Yusuke","family":"Tsuda","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Medicine, Human Genome Center Institute of Medical Science, University of Tokyo  Tokyo Japan"},{"name":"Department of Orthopedic Surgery University of Tokyo  Tokyo 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