THE WILMS-TUMOR (WT1) GENE IS MUTATED IN A SECONDARY LEUKEMIA IN A WAGR PATIENT

The Wilms tumour (WT1) gene was first localized through its deletion i n individuals with the WAGR syndrome (Wilms tumour, aniridia, genitour inary abnormalities and mental retardation). Such individuals have a 3 0-50% lifetime risk of developing Wilms tumour and carry constitutiona l interstitial deletions of chromosome 11p13, including the WT1 gene. Second primary tumours occurring in such individuals might also be rel ated to their genetic predisposition to cancer, as shown for hereditar y retinoblastoma. We have found a mutation in the zinc finger region o f the remaining WT1 allele in a case of acute myeloid leukaemia develo ping in a Wilms tumour survivor with the WAGR syndrome. This mutation would be predicted to disrupt DNA binding by this developmentally regu lated transcription factor. This finding implicates the WT1 gene in th e regulation of myelopoiesis and suggests that WT1 mutations may be fo und in some sporadic leukaemias.