Familial Wilms tumor.

Wilms tumor (WT), an embryonic tumor arising from undifferentiated renal mesenchyme, has been a productive model for understanding the role of genes in both tumorigenesis and normal organogenesis. Approximately 2% of WT patients have a family history of WT, and even sporadic WT is thought to have a strong genetic component to its etiology. Familial WT cases generally have an earlier age of onset and an increased frequency of bilateral disease, although there is variability among WT families, with some families displaying later than average ages at diagnosis. One WT gene, WT1 at 11p13, has been cloned, but only a minority of tumors carry detectable mutations at that locus, and it can be excluded as the predisposition gene in most WT families. Two familial WT genes have been localized, FWT1 at 17q12-q21 and FWT2 at 19q13.4; lack of linkage in some WT families to either of these loci implies the existence of at least one additional familial WT gene. Originally modeled as the inheritance of a mutation in a tumor suppressor gene, molecular analysis of familial tumors not linked to 11p13 have provided data suggesting that this model may be overly simplistic and/or not applicable to all WT families. Identification of the FWT1 and FWT2 genes will help clarify this and will also likely aid in our understanding in general of the roles of the various WT genes and their genetic interactions in the development of WT. Copyright 2004 Wiley-Liss, Inc.