title: Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor.
abstract: Desmoplastic small round cell tumor is a recently recognized distinctive tumor shown to be associated with a recurrent translocation, t(11;22)(p13;q12), and rearrangement of the genes for Ewing sarcoma (EWS) and Wilms tumor (WT1). A genomic DNA fragment containing the EWS-WT1 gene fusion has been isolated from a desmoplastic small round cell tumor, and the breakpoint has been characterized. The breakpoints involve the intron between EWS exons 7 and 8 and the intron between WT1 exons 7 and 8. Chimeric transcripts corresponding to the fusion gene were detected in four of six cases studied. Analysis of these transcripts show an in-frame fusion of RNA encoding the amino-terminal domain of EWS to both alternatively spliced forms of the last three zinc fingers of the DNA-binding domain of WT1. Desmoplastic small round cell tumor represents the third tumor type associated with translocation of EWS and the first tumor associated with consistent translocation of WT1. The chimeric products are predicted to modulate transcription at WT1 target sites and contribute to development of this unique tumor.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: W L
authors.initials: WL
authors.lastname: Gerald
authors.forename: J
authors.initials: J
authors.lastname: Rosai
authors.forename: M
authors.initials: M
authors.lastname: Ladanyi
mesh_terms: D000008:Abdominal Neoplasms / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002678:Chimera; D002880:Chromosomes, Human, Pair 11; D002892:Chromosomes, Human, Pair 22; D003001:Cloning, Molecular; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016162:Genes, Wilms Tumor; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D013899:Thoracic Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D025721:WT1 Proteins
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D012334:RNA, Neoplasm; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D014157:Transcription Factors; D025721:WT1 Proteins