Clinical relevance of mutations in the Wilms tumor suppressor 1 gene WT1 and the cadherin-associated protein beta1 gene CTNNB1 for patients with Wilms tumors: results of long-term surveillance of 71 patients from International Society of Pediatric Oncology Study 9/Society for Pediatric Oncology.

Background: Mutations in the Wilms tumor (WT) suppressor 1 gene (WT1) and the cadherin-associated protein beta1 gene (CTNNB1) are found predominantly in stromal type WT, defining a genetic subgroup. The clinical relevance of these mutations remains to be determined.

Methods: A long-term follow-up study was performed for 71 patients (International Society of Pediatric Oncology Study 9/Society for Pediatric Oncology; n = 77 tumors) with known molecular genetic status.

Different CTNNB1 mutations as molecular genetic proof for the independent origin of four Wilms tumours in a patient with a novel germ line WT1 mutation.

We describe a patient with a novel WT1 pS50X germ line mutation, who developed bilateral Wilms tumours, both with stromal-type histology. Both tumours showed loss of the wild type WT1 allele (loss of heterozygosity (LOH)) and a tumour specific mutation in catenin beta1 (CTNNB1), S45P in the left and Delta45S in the right tumour. Molecular analysis of microdissected cells from the left tumour revealed the same S45P CTNNB1 mutation in blastema, tubuli, stroma and muscle, and a different CTNNB1 mutation (T41A) in stromal cells isolated from another area of the same slide.