A novel EWS-WT1 gene fusion product in desmoplastic small round cell tumor is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene

Haim Werner, Gila Idelman, Moran Rubinstein, Patrick Pattee, Srinivasa R. Nagalla, Charles Roberts

    Research output: Contribution to journalArticle

    36 Citations (Scopus)

    Abstract

    Desmoplastic small round cell tumor (DSRCT) is a primitive sarcoma characterized by a recurrent chromosomal translocation, t(11;22)(p13;q12), which fuses the 5′ exons of the EWS gene to the 3′ exons of the WT1 gene. EWS-WT1 chimeras are heterogeneous as a result of fusions of different regions of the EWS gene to the WT1 gene. We report here a rare and novel EWS-WT1 variant, EWS-WT1 5/10, in a 6-year-old boy diagnosed with DSRCT and analyze the potential transactivation effect of the fusion oncoprotein. The predicted product is comprised of the N-terminal transactivation domain of EWS and lacks any sequence derived from the WT1 gene product. Nonetheless, the truncated protein was able to stimulate expression of the insulin-like growth factor-I receptor gene, a potent antiapoptotic receptor tyrosine kinase with potentially important roles in DSRCT etiology. These findings raise the possibility that the oncogenic potential of EWS-WT1 fusions is not necessarily a consequence of the fusion protein product per se.

    Original languageEnglish (US)
    Pages (from-to)84-90
    Number of pages7
    JournalCancer Letters
    Volume247
    Issue number1-2
    DOIs
    StatePublished - Mar 8 2007

    Fingerprint

    Desmoplastic Small Round Cell Tumor
    IGF Type 1 Receptor
    Trans-Activators
    Gene Fusion
    Genes
    Transcriptional Activation
    Exons
    Genetic Translocation
    Oncogene Proteins
    Receptor Protein-Tyrosine Kinases
    Sarcoma
    Proteins

    Keywords

    • DSRCT
    • EWS-WT1
    • IGF receptor
    • Insulin-like growth factor-I

    ASJC Scopus subject areas

    • Cancer Research
    • Molecular Biology
    • Oncology

    Cite this

    A novel EWS-WT1 gene fusion product in desmoplastic small round cell tumor is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene. / Werner, Haim; Idelman, Gila; Rubinstein, Moran; Pattee, Patrick; Nagalla, Srinivasa R.; Roberts, Charles.

    In: Cancer Letters, Vol. 247, No. 1-2, 08.03.2007, p. 84-90.

    Research output: Contribution to journalArticle

    Werner, Haim ; Idelman, Gila ; Rubinstein, Moran ; Pattee, Patrick ; Nagalla, Srinivasa R. ; Roberts, Charles. / A novel EWS-WT1 gene fusion product in desmoplastic small round cell tumor is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene. In: Cancer Letters. 2007 ; Vol. 247, No. 1-2. pp. 84-90.
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    abstract = "Desmoplastic small round cell tumor (DSRCT) is a primitive sarcoma characterized by a recurrent chromosomal translocation, t(11;22)(p13;q12), which fuses the 5′ exons of the EWS gene to the 3′ exons of the WT1 gene. EWS-WT1 chimeras are heterogeneous as a result of fusions of different regions of the EWS gene to the WT1 gene. We report here a rare and novel EWS-WT1 variant, EWS-WT1 5/10, in a 6-year-old boy diagnosed with DSRCT and analyze the potential transactivation effect of the fusion oncoprotein. The predicted product is comprised of the N-terminal transactivation domain of EWS and lacks any sequence derived from the WT1 gene product. Nonetheless, the truncated protein was able to stimulate expression of the insulin-like growth factor-I receptor gene, a potent antiapoptotic receptor tyrosine kinase with potentially important roles in DSRCT etiology. These findings raise the possibility that the oncogenic potential of EWS-WT1 fusions is not necessarily a consequence of the fusion protein product per se.",
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