LINKAGE OF FAMILIAL WILMS-TUMOR PREDISPOSITION TO CHROMOSOME-19 AND A2-LOCUS MODEL FOR THE ETIOLOGY OF FAMILIAL TUMORS

Familial predisposition to Wilms' tumor (WT), a childhood kidney tumor , is inherited as an autosomal dominant trait, For most WT families st udied, the 11p13 gene WT1 and genomic regions implicated in tumorigene sis in a subset of tumors can be ruled out as the site of the familial predisposition gene, Following a genome-wide genetic linkage scan, we have obtained strong evidence (log of the odds ratio = 4.0) in five f amilies for an inherited WT predisposition gene (FWT2) at 19q13.3-q13. 4. In addition, we observed loss of heterozygosity at 19q in tumors fr om individuals from two families in which 19q can be ruled out as the site of the inherited predisposing mutation, From these data, we hypot hesize that alterations at two distinct loci are critical rate-limitin g steps in the etiology of familial WTs.