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Paper Chase

The Wilms tumour gene WT1 is expressed in murine mesoderm-derived tissues and mutated in a human mesothelioma.

Nat. Genet.. 8 1, 1993;4(4):415-20.
Park S, Schalling M, Bernard A, Maheswaran S, Shipley GC, Roberts D, Fletcher J, Shipman R, Rheinwald J, Demetri G.

Massachusetts General Hospital Cancer Center, Charlestown 02129.


The tumour suppressor gene WT1 encodes a transcription factor expressed in tissues of the genito-urinary system. Inactivation of this gene is associated with the development of Wilms tumour a pediatric kidney cancer. We show that WT1 is also expressed at high levels in many supportive structures of mesodermal origin in the mouse. We also describe a case of adult human mesothelioma, a tumour derived from the peritoneal lining, that contains a homozygous point mutation within WT1. This mutation, within the putative transactivation domain, converts the protein from a transcriptional repressor of its target sequence to a transcriptional activator. The role of WT1 in normal development thus extends to diverse structures derived from embryonic mesoderm and disruption of WT1 function contributes to the onset of adult, as well as pediatric, tumours.