FUSION OF A FORK HEAD DOMAIN GENE TO PAX3 IN THE SOLID TUMOR ALVEOLARRHABDOMYOSARCOMA

We have examined the structure and expression of the products associat ed with the t(2;13)(q35;q14) translocation associated with alveolar rh abdomyosarcoma. The chromosome 13 gene (FKHR) is identified as a membe r of the fork head domain family of transcription factors characterize d by a conserved DNA binding motif. Polymerase chain reaction analysis demonstrates that a 5' PAX3-3' FKHR chimaeric transcript is expressed in all eight alveolar rhabdomyosarcomas investigated. Immunoprecipita tion experiments detect the predicted fusion protein. These findings i ndicate that the t(2;13) generates a potentially tumorigenic fusion tr anscription factor consisting of intact PAX3 DNA binding domains, a tr uncated fork head DNA binding domain and C-terminal FKHR regions.