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.
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.
Rauscher
F J
FJ
Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Benjamin
L E
LE
Fredericks
W J
WJ
Morris
J F
JF
D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D002648:Child; D002880:Chromosomes, Human, Pair 11; D002892:Chromosomes, Human, Pair 22; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016162:Genes, Wilms Tumor; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009857:Oncogenes; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000235:genetics*; D018228:Sarcoma, Small Cell / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014178:Translocation, Genetic; D009396:Wilms Tumor / Q000235:genetics
D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins