Nature Genetics
5, 363 - 367 (1993)
doi:10.1038/ng1293-363
Inactivation of WT1 in nephrogenic rests, genetic precursors to Wilms' tumourSeon Park1, Amy Bernard1, Kevin E. Bove2, Donald A. Sens3, Debra J. Hazen-Martin3, A. Julian Garvin3
& Daniel A. Haber1
1Laboratory of Molecular Genetics, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts 02129, USA
2Deparment of Pathology, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA
3Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA Correspondence should be addressed to D.A.H. Nephrogenic rests consist of foci of primitive renal cells, typically microscopic, that are found within the normal kidney tissue of children with Wilms' tumour. To study the relationship between nephrogenic rests and the associated tumours, we screened these lesions for mutations in the 11p13 Wilms' tumour suppressor gene, WT1. In two cases in which the Wilms' tumour contained a somatic WT1 mutation, the nephrogenic rest had the identical mutation. Nephrogenic rests and Wilms' tumours are therefore topographically distinct lesions that are clonally derived from an early renal stem cell. Inactivation of WT1 appears to be an early genetic event which can lead to the formation of nephrogenic rests, enhancing the probability that additional genetic hits will lead to Wilms' tumour.
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