Wilms' tumors and malformation complexes

Wilms' tumor is an embryonal tumor which is derived from metanephric metanephric blastema. The occurrence of both sporadic and hereditary forms, along with various congenital abnormalities of Wilms' tumor suggest that the tumors develop when a predisposing germ line mutation is accompanied by a second mutation. The existence of both gross chromosomal abnormalities has led to the genetic characterization of a number of loci involved in the development of Wilms' tumor. A tumor suppressor gene for Wilms' tumor, WT1, has been isolated from the 11p13 region. The product of this gene is a transcription factor with four zinc fingers. Because of expression of WT1 is limited to the developing glomeruli of the kidneys and the genital ridge, it is thought to have a functional role in renal and gonadal organogesis. Thus dysfunction of WT1 causes loss of normal regulation of proliferation and leads to tumor formation and occurrence of Wilms' tumor anomaly complexes. The role of the imprinting genes, H19 and IGF2 in oncogenesis of Wilms' tumors are also discussed.