Raised risk of Wilms tumour in patients with aniridia and submicroscopic WT1 deletion.
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.
van Heyningen
Veronica
V
Hoovers
Jan M N
JM
de Kraker
Jan
J
Crolla
John A
JA
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015783:Aniridia / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics* / Q000648:ultrastructure; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D016162:Genes, Wilms Tumor; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008853:Microscopy; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000172:deficiency / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D009396:Wilms Tumor / Q000453:epidemiology / Q000235:genetics*
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins