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  • Original Paper
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Transcriptional regulation of IGF-I receptor gene expression by novel isoforms of the EWS-WT1 fusion protein

Oncogene volume 21, pages 1890–1898 (2002)Cite this article

Abstract

The EWS family of genes is involved in numerous chromosomal translocations that are characteristic of a variety of sarcomas. A recently described member of this group is desmoplastic small round cell tumor (DSRCT), which is characterized by a recurrent t(11;22)(p13;q12) translocation that fuses the 5′ exons of the EWS gene to the 3′ exons of the WT1 gene. The originally described chimera comprises exons 1–7 of EWS and exons 8–10 of WT1. We have previously reported that the WT1 protein represses the expression of the IGF-I receptor gene, whereas the EWS(1–7)-WT1(8–10) fusion protein activates IGF-I receptor gene expression. It has recently become apparent that EWS-WT1 chimeras produced in DSCRT are heterogeneous as a result of fusions of different regions of the EWS gene to the WT1 gene. We have recently characterized additional EWS-WT1 translocations that involve the juxtaposition of EWS exons 7 or 8 to WT1 exon 8, and an EWS-WT1 chimera that lacks EWS exon 6. The chimeric transcription factors encoded by these various translocations differ in their DNA-binding characteristics and their ability to transactivate the IGF-I receptor promoter. These data suggest that the molecular pathology of DSRCT is more complex than previously appreciated, and that this diversity may provide the foundation for predictive genotype-phenotype correlations in the future.

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Abbreviations

IGF-I-R:

insulin-like growth factor-I receptor

DSRCT:

desmoplastic small round cell tumor

EWS:

Ewing's Sarcoma

WT:

Wilms' tumor

RT–PCR:

reverse transcription polymerase chain reaction

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Acknowledgements

This work was performed in partial fulfillment of the requirements for the MSc degree by Ina Finkeltov, in the Sackler Faculty of Medicine, Tel Aviv University. HW is the recipient of a Guastalla Fellowship from the Rashi Foundation, Israel. This work was supported by a grant from the Israel Cancer Association to H Werner and by NIH grant DK50810 to CT Roberts.

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Author notes

  1. Scott Kuhn

    Present address: Agritope, Inc., Beaverton, 97008, OR, USA

Authors and Affiliations

  1. Department of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, 69978, Israel

    Ina Finkeltov, Tova Glaser, Gila Idelman & Haim Werner

  2. Division of Clinical Science, Medicine Branch, National Cancer Institute, NIH, Bethesda, 20889, Maryland MD, USA

    John J Wright

  3. Department of Pediatrics, Oregon Health Sciences University, Portland, 97201, Oregon OR, USA

    Scott Kuhn & Charles T Roberts Jr

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Correspondence to Haim Werner.

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Finkeltov, I., Kuhn, S., Glaser, T. et al. Transcriptional regulation of IGF-I receptor gene expression by novel isoforms of the EWS-WT1 fusion protein. Oncogene 21, 1890–1898 (2002). https://doi.org/10.1038/sj.onc.1205042

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