Fusion of the EWS1 and WT1 genes as a result of the t (11; 22) (p13; q12) translocation in desmoplastic small round cell tumors - Benjamin - 1996 - Pediatric Blood & Cancer - Wiley Online Library

Fusion of the EWS1 and WT1 genes as a result of the t (11; 22) (p13; q12) translocation in desmoplastic small round cell tumors - Benjamin - 1996 - Pediatric Blood & Cancer - Wiley Online Library

Fusion of the EWS1 and WT1 genes as a result of the t (11; 22) (p13; q12) translocation in desmoplastic small round cell tumors - Benjamin - 1996 - Pediatric Blood & Cancer - Wiley Online Library

The isolation and molecular analysis of genes that cause and / or predispose to Wilms' tumor have yielded fascinating insights into the role of tissue-specific gene regulation in both development and disease processes. Analysis of the WT1 transcription factor has clearly established its role in Wilms tumorigenesis and a broader role in both urogenital organogenesis and mesenchymal cell differentiation events. Clearly, loss of function mutations in WT1 is correlated with aberrant function as a regulator of gene expression, ultimately resulting in neoplastic transformation in the developing kidney. WT1 structure and / or function can be associated with other types of malignancies, possibly reflecting WT1 broader role in mesenchymal differentiation. To this end, we have analyzed the rare solid tumor designated I ntra- B D D esmoplastic S mall < (p13; q12) involving the R ound C S arcoma (IADSRCT) which often displays a recurrent chromosomal translocation t (11; in> WT1 genomic locus. We have shown that the EWS1 gene from chromosome 22q12 is fused to the WT1 gene in IADSRCT and that the fusion protein is produced which functions as a potent activator of transcription. Our results suggest that WT1 has sustained the gain-of-function alteration as a result of this fusion and that the fusion gene functions as a dominant oncogene in this disease. Thus, the WT1 locus may be the target for both gain and loss of function mutations resulting in different disease outcomes. A summary of our ongoing analysis of the EWS-WT1 fusion gene is presented. © 1996 Wiley-Liss, Inc.

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