GENETIC EVENTS PREDISPOSING TO WILMS\u27 TUMOR

Wilms\u27 tumor (WT) is a childhood embryonic tumor of the kidney. In some cases, WT has been associated with a chromosome deletion in the region 11p13. The majority of WT cases, however, have normal karyotypes with no discernable deletions or rearrangements of chromosome 11. To study the genetic events predisposing to the development of WT, I have used a number of gene markers specific for chromosome 11. Gene probes for human catalase and apolipoprotein A1 were localized to chromosome 11 by in situ hybridization. A number of other probes previously mapped to chromosome 11 were also used. Nine WT patients who were heterozygous for at least one 11p marker were shown to lose heterozygosity in their tumor DNA. Gene dosage experiments demonstrated that two chromosomes 11 were present although loss of heterozygosity had occurred in all but two cases. By using gene probes from the short and long arms of chromosome 11, I discerned that loss of heterozygosity was due to somatic recombination in four cases, chromosome deletion in two cases, and chromosome loss and reduplication or somatic recombination in these cases. Examination of DNAs from the parents of six of these patients indicated that the alleles that were lost in tumor tissues were alleles inherited from the mother. In sporadic WT cases one would expect the loss of alleles to be random. These data suggest that the loss of alleles resulting in the development of WT is not a random event, however, the significance of this is not known