title: 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.
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.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, 69978 Tel Aviv, Israel. hwerner@post.tau.ac.il
authors.forename: Haim
authors.initials: H
authors.lastname: Werner
authors.forename: Gila
authors.initials: G
authors.lastname: Idelman
authors.forename: Moran
authors.initials: M
authors.lastname: Rubinstein
authors.forename: Patrick
authors.initials: P
authors.lastname: Pattee
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Nagalla
authors.forename: Charles T
authors.initials: CT
authors.lastname: Roberts
mesh_terms: D002648:Child; D002880:Chromosomes, Human, Pair 11; D002892:Chromosomes, Human, Pair 22; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000494:pharmacology*; D034802:RNA-Binding Protein EWS / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D018228:Sarcoma, Small Cell / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection; D014178:Translocation, Genetic; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D015514:Oncogene Proteins, Fusion; D034802:RNA-Binding Protein EWS; D025721:WT1 Proteins; D017526:Receptor, IGF Type 1