Eel WT1 sequence and expression in spontaneous nephroblastomas in Japanese eel

Nephroblastomas spontaneously developing in Japanese eel reared at farms for 5 to 9months after collection from the wild [Masahito et al., Cancer Res., 52 (1992) 2575-2579] were investigated to cast light on the role of Wilms' tumor 1 gene (WT1) in eel kidney tumorigenesis. Cloning of the WT1 counterpart, EWT1, revealed that conservation of an alternative splice II site, located between the third and fourth zinc fingers, was conserved. The zinc finger domain was highly conserved. The transregulator region, sequences corresponding to exons 4 and 5 in WT1, were lacking in EWT1 cDNA. EWT1 was found to be expressed in kidney, testis and spleen and in situ hybridization revealed dark-stained immature cells in elver kidney to be positive. Although no EWT1 gene mutations were found in 38 eel nephroblastomas, 26 polymorphic nucleic acid changes were observed. Aberrant WT1 expression was noted in epithelial (12 out of 27; 44%) and nephroblastic cell histological types (three out of five; 60%) of eel nephroblastomas. On in situ hybridization the EWT1 expressive cells resembled human blastema cells, similar to those in human Wilms' tumor. These data demonstrated strong signals that the EWT1 protein may function in the development of eel kidney and play a role in genesis of nephroblastomas as in mammals.