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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Cell Differentiation / genetics
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Child
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Chromosomes, Human, Pair 11
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Chromosomes, Human, Pair 22
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Cloning, Molecular
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DNA Primers / genetics
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DNA, Neoplasm / genetics
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DNA, Neoplasm / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Genes, Wilms Tumor*
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Humans
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Kidney Neoplasms / genetics
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Molecular Sequence Data
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Mutation*
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Oncogenes*
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Phenotype
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Sarcoma, Ewing / genetics*
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Sarcoma, Small Cell / genetics*
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Sarcoma, Small Cell / metabolism
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Transcriptional Activation
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Translocation, Genetic
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Wilms Tumor / genetics
Substances
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DNA Primers
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DNA, Neoplasm
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DNA-Binding Proteins
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Recombinant Fusion Proteins