Structural rearrangements of the WT1 gene in Wilms' tumour cells.

We have analysed 55 Wilms' tumour DNAs using the cDNA from the candidate Wilms' predisposition gene, WT1. One tumour, GOS 129, shows a partial homozygous deletion involving only the 3'-most exon of the gene. An adjacent 3' DNA sequence, J7-18, which lies on the same NotI fragment as WT1, is present in GOS 129. Thus, this partial deletion does not extend to the adjacent unmethylated 3' HTF island. These data support the candidature of WT1 as a Wilms' predisposition gene. Tumour GOS 129 has become homozygous as a result of a mitotic recombination event proximal to WT1. Three other tumours showed abnormally sized bands on Southern blot analysis which appear to reflect internal heterozygous rearrangements involving the 5' end of the gene. One of these tumours was from a bilaterally-affected patient and the other 3 were from stage III or IV tumours.