NOVEL WT1 MUTATION, 11P LOH, AND T(7-12) (P22-Q22) CHROMOSOMAL TRANSLOCATION IDENTIFIED IN A WILMS-TUMOR CASE

About 5-10% of sporadic Wilms' tumors (WT) are associated with mutatio ns in the Wilms' tumor I gene (WT1). More than 90% of patients with De nys-Drash syndrome (DDS; characterized by renal nephropathy, gonadal a nomaly, and predisposition to WT) show constitutional intragenic WT1 m utations. We describe a novel WT1 stop-mutation in exon 2. This hetero zygous germline mutation was detected in a one-year-old girl who was b ilaterally affected with Wilms' tumor but without any other clinical m anifestations of DDS. The C-to-A transversion is predicted to result i n a polypeptide comprising only the first 165 amino acids of the WT1 p rotein. Loss of heterozygosity (LOH) studies comparing tumor DNA with lymphocyte DNA revealed LOH for the entire short arm of chromosome I I in tumor tissue. In addition to the chromosome I I lesions, the tumor showed a seemingly balanced chromosomal translocation t(7;12) (p22;q2 2) as the only visible cytogenetic aberration. (C) 1998 Wiley-Liss, In c.