Genetics of Wilms' tumor: A blend of aberrant development and genomic imprinting

Wilms' tumor or nephroblastoma (WT), one of the most common childhood solid tumors (1:10,000, 8% of childhood tumors), is probably the one that best deserves the designation of embryonal tumor. Wilms' tumors are composed of three major elements in variable proportions: compact areas of blastemal cells, tubular structures of various sizes and fibrous or mixoid stroma containing elongated stellate-shaped large round cells. These components are reminiscent of normal human nephrogenesis, known to be initiated by the ingrowth of the ureteral bud into the metanephrogenic mesenchyma which then condenses and forms the different portions of the nephron. These tumors thus show a remarkable mimicry of the normal nephrogenic processes, although in an extravagant mode leading to incompletely differentiated structures with as many dead ends as a labyrinth [1]. These structures are accompanied, in a minority of cases, by heterologous ectopic tissues of mesodermal origin including bone, cartilage and skeletal muscle [2].