INACTIVATION OF WT1 IN NEPHROGENIC RESTS, GENETIC PRECURSORS TO WILMS-TUMOR

Nephrogenic rests consist of foci of primitive renal cells, typically microscopic, that are found within the normal kidney tissue of childre n with Wilms' tumour. To study the relationship between nephrogenic re sts and the associated tumours, we screened these lesions for mutation s in the 11p13 Wilms' tumour suppressor gene, WT1. In two cases in whi ch 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 deri ved from an early renal stem cell. Inactivation of WT1 appears to be a n early genetic event which can lead to the formation of nephrogenic r ests, enhancing the probability that additional genetic hits will lead to Wilms' tumour.