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Fusion of PAX3 to a Member of the Forkhead Family of Transcription Factors in Human Alveolar Rhabdomyosarcoma¹

Departments of Experimental Oncology [D. N. S., J. E. S., B. L.], Hematology/Oncology [D. N. S.], Pathology [J. R. D.], Tumor Cell Biology [J. R. D.], and Virology and Molecular Biology [C. W. N.], St. Jude Children's Research Hospital, Memphis, Tennessee 38105, and Departments of Pediatrics [D. N. S.] and Pathology [J. R. D., C. W. N.], University of Tennessee College of Medicine, Memphis, Tennessee 38163

Alveolar rhabdomyosarcoma, a malignant tumor of skeletal muscle, is characterized by a chromosomal translocation, t(2;13)(q35;q14). This translocation is associated with a structural rearrangement of the gene encoding PAX3, a presumed transcriptional regulator expressed exclusively during embryogenesis. The breakpoint results in a fusion between PAX3 and a gene provisionally named ALV, a novel member of the forkhead family of transcription factors. In PAX3-ALV, the structural integrity of both PAX3 DNA-binding regions, the paired box and homeodomain, are retained while the putative transcriptional activation domain of PAX3 is replaced by the bisected forkhead DNA-binding domain of ALV. Formation of chimeric transcription factors has now been implicated in diverse human tumors of myogenic, hematopoietic, neuroectodermal, and adipocytic origin, suggesting that transcriptional deregulation is a common mechanism of tumorigenesis.

¹ Supported in part by Grant CA-23099 and Cancer Center CORE Grant CA-21765 from the NIH and by the American Lebanese Syrian Associated Charities (ALSAC).

² To whom requests for reprints should be addressed, at the Department of Experimental Oncology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105.

Received 9/29/93. Accepted 10/ 1/93.

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