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Laboratory for Molecular Oncology, Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, Herestraat 49, B-3000 Leuven, Belgium [J. M. W. G., E. F. P. M. S., W. J. M. V.], and Laboratory of Cancer Genetics, Department of Pathology, Göteborg University, Göteborg, Sweden [E. R., G. S.]
The developmentally regulated HMGIC gene, which encodes an architectural transcription factor, has recently been linked to the pathogenesis of benign solid tumors with chromosome aberrations involving 12q1315. Among these tumors are pleomorphic adenoma of the salivary glands, lipoma, uterine leiomyoma, hamartomas of the breast and lung, fibroadenoma of the breast, angiomyxoma, and endometrial polyps. For most tumor types, however, the translocation partners are variable. At present, no translocation partner genes of HMGIC are known for pleomorphic adenomas. Here, we report that in a primary pleomorphic adenoma of the parotid gland, the FHIT gene, which spans the chromosome 3p14.2 fragile site FRA3B, and is frequently disrupted in tumors, acts as a fusion partner of HMGIC. In addition to normal HMGIC and FHIT transcripts, an HMGIC/FHIT hybrid transcript as well as its reciprocal counterpart, FHIT/HMGIC, were found to be expressed by reverse transcription-PCR. The results establish the concurrent disruption of two tumor-associated genes in a benign tumor.
1 This work was supported in part by the National Fonds voor Wetenschappelijk Onderzoek, the Geconcerteerde Onderzoekacties 19921996, the Flanders Interuniversity Institute for Biotechnology, the Biomed 1 Concerted Action "Molecular Cytogenetics of Solid Tumors" (CT92-0156), the ASLK Programma voor Kankeronderzoek, the Swedish Cancer Society, and the IngaBritt and Arne Lundbergs Research Foundation. J. M. W. G. is a Research Assistant of the Nationaal Fonds voor Wetenschappelijk Onderzoek (Kom op tegen Kanker, Belgium).
2 To whom requests for reprints should be addressed. Phone: 32-16-345987; Fax: 32-16-346073; E-mail: wim.vandeven@med.kuleuven.ac.be.
Received 9/20/96. Accepted 11/20/96.
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