EWS AND WT-1 GENE FUSION IN DESMOPLASTIC SMALL ROUND-CELL TUMOR OF THE ABDOMEN

Chromosome translocations found in neoplasms often result in the creat ion of hybrid genes encoding chimeric proteins. This case study descri bes a patient with desmoplastic small round cell tumor (DSRCT) of the abdomen, an aggressive neoplasm characterized by translocation of chro mosomes 11 and 22. Southern hybridization showed that the Ewing sarcom a gene (EWS) gene was rearranged in the DSRCT. Reverse transcriptase-p olymerase chain reaction analysis of tumor cell RNA revealed that exon s 1 to 7 of the EWS gene were joined to exons 8 to 10 of the Wilms' Tu mor-1 (WT-1) gene resulting in the production of a chimeric message. T he WT-1 and EWS genes encode DNA and RNA binding proteins involved in Wilms' tumor and Ewing sarcoma pathogenesis, respectively. The fusion of these two genes in DSRCT results in the production of a putatively oncogenic protein composed of the zinc finger DNA binding domains of W T-1 linked to potential transcriptional regulatory domains of EWS. DNA sequencing revealed the genomic breakpoints of translocation on chrom osomes 11 and 22. The genomic breakpoint on chromosome 22 occurred in EWS intron 7 just 2 nucleotides 3' of exon 7. Polymerase chain reactio n-based assays were developed that could detect the fused genes in the DSRCT tumor using either RNA or genomic DNA. The potential diagnostic use of these assays is discussed. Copyright (C) 1995 by W.B. Saunders Company