Raised risk of Wilms tumour in patients with aniridia and submicroscopic WT1 deletion
- 1MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK
- 2Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands
- 3Department of Pediatric Oncology, Emma Children’s Hospital, Academic Medical Centre, Amsterdam, The Netherlands
- 4Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, UK
- Veronica van Heyningen, MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK;
- Received 30 April 2007
- Revised 3 July 2007
- Accepted 5 July 2007
- Published Online First 14 July 2007
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 those with visible deletions of the WT1 tumour suppressor gene.
Methods: To determine which subjects had WT1 deletions, high-resolution chromosomal deletion analysis of the 11p13 region was carried out in 193 people 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 patients with aniridia have intragenic mutations, a proportion has deletions that also include the nearby WT1 gene. Fluorescence in situ hybridisation (FISH) analysis of patients with aniridia identifies people with WT1 deletions regardless of whether 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 subjects in whom WT1 was deleted, 77% with submicroscopic deletions (detectable only by high-resolution FISH analysis) presented with Wilms tumour compared with 42.5% with visible deletions (detectable by microscopy). This difference was significant.
Conclusions: High-resolution deletion analysis is a useful tool for assessing the risk of Wilms tumour in neonates with aniridia. People with submicroscopic WT1 deletions have a significantly increased risk of Wilms tumour, and a high level of vigilance should be maintained in such cases.
Competing interests: none declared.
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