Abstract

Objective: The aim of this study was to determine if there is a significant difference in the risk of developing Wilms tumour between patients with submicroscopic and visible deletions of the WT1 tumour suppressor gene.

Methods: To ascertain individuals with WT1 deletions, high resolution chromosomal deletion analysis of the 11p13 region was carried out in 193 individuals with aniridia. The rationale for this was that aniridia is caused by loss of function of one copy of the PAX6 gene, and although most aniridia patients have intragenic mutations, a proportion will have deletions that also include the nearby WT1 gene. FISH analysis of aniridia patients identifies individuals with WT1 deletions regardless of whether or not they have Wilms tumour, allowing the deletion size to be correlated with clinical outcome.

Results: Wilms tumour was not observed in any case without a WT1 deletion. Of those individuals in which WT1 was deleted, 77% with submicroscopic deletions (detectable only by high-resolution FISH analysis) presented with Wilms tumour compared to 42.5% with visible deletions (detectable by microscopy). This difference was statistically significant.

Conclusions: High-resolution deletion analysis is a useful tool for assessing the risk of Wilms tumour in neonates with aniridia. Individuals with submicroscopic WT1 deletions have a significantly increased risk of Wilms tumour and a high level of vigilance should be maintained in such cases.