The role of WT1 in oncogenesis: tumor suppressor or oncogene?

Although originally identified as a tumor suppressor gene, WT1 is overexpressed in a variety of hematologic malignancies and solid tumors, including acute leukemia, breast cancer, malignant mesothelioma, renal cell carcinoma, and others. Overexpression of both wild-type and mutant WT1 has been reported. In some cases, this finding represents overexpression of a gene that should be expressed at lower levels, but in other cases, WT1 is expressed at high levels in a tissue type in which there is normally no expression at all. In this review, the mechanisms of altered WT1 expression are explored, including changes in promoter methylation. WT1 target genes that may be important for oncogenesis are discussed, as is the use of WT1 expression as a diagnostic tool. The prognostic implications of altered WT1 expression and the potential for immunotherapy aimed at WT1 are also discussed.