A Third Wilms' Tumor Locus on Chromosome loq1

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 WTl gene located in chromosome 11pi3 and an unidentified gene(s) within chromosome 11p15 have been implicated in Wilms' 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 alíele loss in a series of Wilms' tumors. We found that in addition to loss on chromosome 11p ( 11 of 25 informative tumors) there was significant loss on chromosome 16q (9 of 45 informative tumors), while the total fre quency of alíeleloss excluding these loci was low (9 of 426 total informative loci). These data indicate that losses of both chromosome lip and 16q alíeles are nonrandom events and suggest that 16q is the location of a third tumor suppressor gene underlying Wilms' tumorigen esis. The parental origin of the lost chromosome 16q alíele was deter mined in eight sporadic tumors. Alíeles of paternal and of maternal origin were each lost in four sporadic tumors indicating that, unlike chromosome lip, alíeles of either parental origin are lost on 16q.