Fusion of EWSR1 with the DUX4 facioscapulohumeral muscular dystrophy region resulting from t(4;22)(q35;q12) in a case of embryonal rhabdomyosarcoma.

Abstract Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma and rarely occurs in adults. There are six main subtypes, each histologically, clinically, and cytogenetically distinct. Embryonal RMS is characterized by chromosomal gains, usually not associated with any consistent structural anomaly. We describe here a case of embryonal RMS in a 19-year-old female patient. The conventional cytogenetic analysis showed a t(4;22)(q35;q12) translocation as the sole cytogenetic change. Complementary fluorescence in situ hybridization analysis showed that the translocation breakpoints were located in the EWSR1 gene at 22q12 and the region of the DUX4 and FSHMD1A at 4q35. This constitutes a novel example of the high frequency of EWSR1 rearrangements in various types of sarcomas as well as of its ability to fuse with a large variety of partner genes. Because DUX4 is involved in myogenic differentiation and cell-cycle control, the striated muscle differentiation observed in the present case might be a direct consequence of the alteration of the DUX4 region generated by the t(4;22). The involvement of the DUX4 region might represent the genetic hallmark of a novel subclass of small round cell tumors.