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American Journal of Pathology, Vol 146, 40-45, Copyright © 1995 by American Society for Investigative Pathology

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Comparative in situ hybridization analysis of PAX2, PAX8, and WT1 gene transcription in human fetal kidney and Wilms' tumors

MR Eccles, K Yun, AE Reeve and AE Fidler
Department of Biochemistry, University of Otago, Dunedin, New Zealand.

Wilms' tumor (WT) is a childhood renal neoplasm with histological features resembling fetal kidney development. Two members of the paired box family of genes, PAX2 and PAX8, are expressed in WT and are potentially involved in its induction. A zinc finger gene, WT1, which is involved in WT induction, encodes a DNA binding protein, and like PAX2 and PAX8 proteins is a transcription factor with an important role in kidney development. We have compared the expression patterns of PAX2, PAX8, and WT1 in fetal kidney and WTs 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 transcription was observed in the glomeruli of fetal kidney until a later stage in development than PAX genes. In WTs all three genes were expressed in the condensed blastema, but WT1 expression was not detectable 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 continued to express PAX genes. It is unlikely that both PAX2 and PAX8 genes would be mutated in WT. However, failure of PAX gene expression to attenuate in WTs may result from mutations involved in the onset of the tumor.

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