title: IRIZIO: a novel gene cooperating with PAX3-FOXO1 in alveolar rhabdomyosarcoma (ARMS).
abstract: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children with an annual incidence of five new cases per million. Alveolar rhabdomyosarcoma (ARMS) is characterized by the t(2;13) or t(1;13) chromosomal translocations, which generate the PAX3-FOXO1 or PAX7-FOXO1 fusion genes, respectively. The oncogenic activity of PAX3-FOXO1 has been demonstrated in vitro and in vivo, yet expression of the fusion protein alone in primary myoblasts or a mouse model is insufficient for tumorigenic transformation. To identify genes cooperating with PAX3-FOXO1 in ARMS tumorigenesis, we generated a retroviral complementary DNA (cDNA) expression library from the Rh30 ARMS cell line. Arf-/- myoblasts expressing PAX3-FOXO1 and the retroviral cDNA library rapidly formed tumors after subcutaneous injection into NOD-SCID mice. Tumors formed by Arf-/-/PAX3-FOXO1/MarX-library myoblasts contained an unknown cDNA, encoding the C-terminus of the Homo sapiens hypothetical protein, FLJ10404, herein named IRIZIO. Expression of full length IRIZIO cDNA also cooperated with PAX3-FOXO1 in the transformation of Arf-/- myoblasts. Given that IRIZIO is expressed at increased levels in RMS, it might contribute to rhabdomyosarcomagenesis in humans.
authors.affiliation: Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Picchione
authors.forename: Colin
authors.initials: C
authors.lastname: Pritchard
authors.forename: Irina
authors.initials: I
authors.lastname: Lagutina
authors.forename: Laura
authors.initials: L
authors.lastname: Janke
authors.forename: Gerard C
authors.initials: GC
authors.lastname: Grosveld
mesh_terms: D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D032446:Myoblasts / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D009857:Oncogenes; D051761:Paired Box Transcription Factors / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D016160:Retinoblastoma Protein / Q000502:physiology; D018232:Rhabdomyosarcoma, Alveolar / Q000209:etiology* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: C558647:FAM193B protein, human; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C471563:PAX3-FOXO1A fusion protein, human; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53