COMPARATIVE IN-SITU HYBRIDIZATION ANALYSIS OF PAX2, PAX8, AND WT1 GENE-TRANSCRIPTION IN HUMAN FETAL KIDNEY AND WILMS-TUMORS

Wilms' tumor (WT) is a childhood renal neoplasm with histological feat ures resembling fetal kidney development. Two members of the paired bo x family of genes, PAX2 and PAX8, are expressed in WT and are potentia lly involved in its induction. A zinc finger gene, WT1, which is invol ved in WT induction, encodes a DNA binding protein, and like PAX2 and PAX8 proteins is a transcription factor with an important role in kidn ey development. We have compared the expression patterns of PAX2, PAX8 , and WT1 in fetal kidney and WT's by in situ hybridization. The PAX2, PAX8, and WT1 genes were transcribed in the condensed mesenchyme and early stages of epithelial differentiation in fetal kidney. WT1 gene t ranscription was observed in the glomeruli of fetal kidney until a lat er stage in development than PAX genes. In WTs all three genes were ex pressed in the condensed blastema, but WT1 expression was not detectab le in the epithelial structures in two WTs. No evidence of attenuation of PAX gene expression was found in WT. These results suggest that in some WTs the expression of WT1 is attenuated in structures that conti nued to express PAX genes. It is unlikely that both PAX2 and PAX8 gene s would be mutated in WT. However, failure of PAX gene expression to a ttenuate in WTs may result from mutations involved in the onset of the tumor.