Intragenic homozygous deletion of the WT1 gene in Wilms' tumor.

One example of intragenic homozygous deletion of the WT1 gene on chromosome 11p13 was found after screening 42 samples of Wilms' tumor DNA from Japanese patients. After construction of a restriction map for the genomic sequence covering the 3' half of the gene, the deletion was analysed at the nucleotide sequence level. The deletion occurred in the patient's germline on his paternal chromosome, and most of the short arm of his maternal chromosome 11 was subsequently lost in the tumor. The size of the deletion was about 8 kb, removing exons 6 and 7 and resulting in premature termination. The deletion seemed to be created by recombination between short homologous sequences found in an Alu repeat, with a 16-bp duplication left at the junction. This case conforms to a two-hit model for the genesis of a certain group of tumors, and supports the hypothesis that WT1 is one of the recessive oncogenes responsible for Wilms' tumor.