IRIZIO: a novel gene cooperating with PAX3-FOXO1 in alveolar rhabdomyosarcoma (ARMS)

Carcinogenesis. 2011 Apr;32(4):452-61. doi: 10.1093/carcin/bgq273. Epub 2010 Dec 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, SCID
  • Myoblasts / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Oncogene Proteins, Fusion / physiology*
  • Oncogenes*
  • Paired Box Transcription Factors / physiology*
  • RNA, Messenger / analysis
  • Retinoblastoma Protein / physiology
  • Rhabdomyosarcoma, Alveolar / etiology*
  • Rhabdomyosarcoma, Alveolar / genetics
  • Tumor Suppressor Protein p53 / physiology


  • FAM193B protein, human
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • PAX3-FOXO1A fusion protein, human
  • Paired Box Transcription Factors
  • RNA, Messenger
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53