Novel Oncogenic Mutations in the WT1 Wilms' Tumor Suppressor Gene: A t(11;22) Fuses the Ewing's Sarcoma Gene, EWS1, to WT1 in Desmoplastic Small Round Cell Tumor

Abstract

These studies suggest that the WT1 tumor suppressor gene, originally identified as a recessive oncogene in Wilms' tumors, is capable of sustaining a gain-of-function mutation which results in its contribution to a completely different disease entity: desmoplastic small round cell tumor. Two independent biochemical functions of WT1, DNA-binding activity and mode of transcriptional regulation, are altered as a consequence of the chromosomal translocation and fusion with EWS. The fusion of EWS and WT1 genes in DSRCT thus provides a unique paradigm for a means by which different alterations of transcription factor function can lead to diverse oncogenic processes.