A unique case of Alveolar Rhabdomyosarcoma with two translocations:t(2;13) and t(1;13), and amplification of N-myc in a 5-year-old child. R. Mosely¹, M. Liu¹, B. Myers¹, M.A. Thompson², T. McCurley², S. Shankar³, V.G. Dev¹, A. Yenamandra¹. 1) Genetics Associates Inc., Nashville, TN; 2) Dept of Pathology, Vanderbilt University School of Medicine, Nashville, TN; 3) Dept of Medicine,Vanderbilt University School of Medicine, Nashville, TN.
   The most common type of rhabdomyosarcoma is alveolar rhabdomyosarcoma (ARMS), characterized by the specific translocation t(2;13)(q35;q14) or its rarer variant, t(1;13)(p36;q14), producing the fusion genes PAX3-FKHR and PAX7-FKHR, respectively. The N-myc gene is also reported to be amplified in a few cases of ARMS. We report a previously healthy, 5-year-old girl who presented with a four-week history of severe back pain and parasthesias in lower extremities. Radiographs of her spine showed a collapsed vertebral body. Further evaluation revealed a large paraspinal mass with intraspinal extension and spinal cord compression. She had widespread metastatic disease involving multiple bony sites and bone marrow. The differential diagnosis was sarcoma or neuroblastoma. The histopathological studies of the biopsy demonstrated that the tumor cells were positive for the muscle marker MyoD1, desmin, CD99, and NSE. The specific neuroendocrine markers chromogranin and synaptophysin were negative, as were antibodies to lymphoid markers and to keratin. Cytogenetic analysis of the patient revealed the translocations t(2;13) and t(1;13). FISH with FKHR breakapart DNA probe revealed that the 3 end of the FKHR sequences of one chromosome 13 had moved to 2q35 whereas the 3 end of the second chromosome 13 that had moved to 1p was deleted. N-myc gene was amplified 15-20 times in about 50% of the cells. PAX3-FKHR and PAX7-FKHR overexpression has been reported to result from two distinct genetic mechanisms. The PAX3-FKHR from altered transcriptional regulation and the PAX7-FKHR from fusion gene amplification. In our case PAX3-FKHR fusion gene seems to be intact while the PAX7-FKHR gene appears to be deleted at the 3end of FKHR along with the N-myc gene amplification. Further analysis of the regulation mechanisms will lead to the understanding of the critical level of gene product for the oncogenic effects of these fusions.