The identification of the novel causative genes in embryonal rhabdomyosarcoma and the elucidation of the molecular mechanism

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Rhabdomyosarcoma is the most common soft tissue tumor seen in children and young adults. Rhabdomyosarcoma can be classified into two major histological subtypes, alveolar and embryonal. In the alveolar subtype, two recurrent chromosomal translocations, t(2;13)(q35;q14) and its variant t(1;13)(p36;q14), have been identified as the specific cytogenetic abnormalities. These translocations create the PAX3-FOXO1 and PAX7-F0X01 fusion genes, respectively. In the embryonal subtype, however, no recurrent chromosomal abnormalities have been identified.In this study, we analyzed the complex chromosomal translocation t(2;8;12) in one case with embryonal rhabdomyosarcoma by means of spectral karyotyping (SKY) and identified a novel translocation involving chromosome band 2q35, which is the locus of PAX3 gene. Furthermore, we identified the novel PAX3 rearrangement using fluorescence in situ hybridization (FISH) analysis. To identify the partner gene located on the 8q breakpoint in this case, we performed sequential FISH analyses using bacterial artificial chromosome (BAC) probes located on 8q. The BAC clones (RP11 series) were selected according to the University of California Santa Cruz (UCSC) Genome Browser (http://genome. ucsc. edu). The results suggested that TIF2 gene (8p11) spanned the 8q breakpoint of complex t(2;8;12). Furthermore, FISH analysis showed the PAX3-TIF2 fusion in tumor cells. Unfortunately, we could not determine the molecular structure of the PAX3-TIF2 fusion gene.To identify others translocations involving the TIF2 gene in rhabdomyosarcoma, we analyzed rhabdomyosarcoma cell lines (Rh2, RD, HKBm, RM2, and Rh30) using FISH. However, no translocations involving the TIF2 gene were detected.