INFREQUENT MUTATION OF THE WT1 GENE IN 77 WILMS-TUMORS

Homozygous deletions in Wilms' tumor DNA have been a key step in the i dentification and isolation of the WT1 gene. Several additional loci a re also postulated to contribute to Wilms' tumor formation. To assess the frequency of WT1 alterations we have analyzed the WT1 locus in a p anel of 77 Wilms' tumors. Eight tumors showed evidence for large delet ions of several hundred or thousand kilobasepairs of DNA, some of whic h were also cytogenetically detected. Additional intragenic mutations were detected using more sensitive SSCP analyses to scan all 10 WT1 ex ons. Most of these result in premature stop codons or missense mutatio ns that inactivate the remaining WT1 allele. The overall frequency of WT1 alterations detected with these methods is less than 15%. While so me mutations may not be detectable with the methods employed, our resu lts suggest that direct alterations of the WT1 gene are present in onl y a small fraction of Wilms' tumors. Thus, mutations at other Wilms' t umor loci or disturbance of interactions between these genes likely pl ay an important role in Wilms' tumor development. (C) 1994 Wiley-Liss, Inc.