A Third Wilms5 Tumor Locus on Chromosome 16q

Loss of heterozygosity studies have been used to identify chromosomal regions which are frequently deleted and thus indicate areas which may harbor tumor suppressor genes. As a result, both the WT1 gene located in chromosome 11 pi3 and an unidentified gene(s) within chromosome 11 pi5 have been implicated in Wilms9 tumorigenesis. Cytogenetic and linkage studies suggest that additional non-chromosome 11 sites are involved in Wilms tumor. Because these sites may also involve loss of heterozygosity, loci on 33 autosomal arms were screened for allele loss in a series of Wilms9 tumors. We found that in addition to loss on chromosome Up (11 of 25 informative tumors) there was significant loss on chromosome 16q (9 of 45 informative tumors), while the total frequency of allele loss excluding these loci was low (9 of 426 total informative loci). These data indicate that losses of both chromosome Up and 16q alleles are nonrandom events and suggest that 16q is the location of a third tumor suppressor gene underlying Wilms9 tumorigenesis. The parental origin of the lost chromosome 16q allele was determined in eight sporadic tumors. Alleles of paternal and of maternal origin were each lost in four sporadic tumors indicating that, unlike chromosome Up, alleles of either parental origin are lost on 16q.