Loss of heterozygosity at chromosome 11p15 in Wilms tumors: identification of two independent regions

Loss of heterozygosity (LOH) on the short arm of chromosome 11 is the most frequent genetic alteration in Wilms tumors, indicating that one or more tumor suppressor genes that map to this chromosomal region are involved in the development of the disease, The WT1 gene located on 11p13 has been characterized but mutations in this gene occur in only about 10% of Wilms tumors, A second locus (WT2) at chromosome 11p15 has also been described in Wilms tumors but thus far efforts to clone the WT2 gene(s) have been frustrated by the large size (similar to 10 Mb) of this region. Using a high-density marker LOH analysis of 11p15.5-15.4, we have refined the location of a Wilms tumor suppressor gene between the markers D11S1318-D11S1288 (similar to 800 kb) within 11p15.5, We have also identified a second, novel region of LOH that spans the markers D11S1338-D11S1323 (similar to 336 kb) at 11p15.5-p15.4. Thus a second distinct locus, in addition to the previously defined WT2, on chromosome 11p15.5, appears to play a role in the development of Wilms tumors.