title: 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.
authors.affiliation: Laboratory of Solid Tumor Genetics, Nice University Hospital, 06107 Nice, France. sirvent.n@chu-nice.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sirvent
authors.forename: Martine
authors.initials: M
authors.lastname: Trassard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ebran
authors.forename: Rita
authors.initials: R
authors.lastname: Attias
authors.forename: Florence
authors.initials: F
authors.lastname: Pedeutour
mesh_terms: D000328:Adult; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22; D002894:Chromosomes, Human, Pair 4; D020732:Cytogenetic Analysis; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008840:Microfilament Proteins; D008854:Microscopy, Electron; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000235:genetics*; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*; D018233:Rhabdomyosarcoma, Embryonal / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D002148:Calmodulin-Binding Proteins; C121257:DUX4L1 protein, human; C500986:EWSR1 protein, human; C101270:FRG1 protein, human; D018398:Homeodomain Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins