RNA polymerase chain reaction detects different levels of four alternatively spliced WT1 transcripts in Wilms' tumors.

A Wilms' tumor susceptibility gene (WT1) localized to 11p13 was recently isolated and shown to be altered in some sporadic Wilms' tumors. This gene encodes a DNA-binding protein with four zinc fingers (ZFs) in the carboxy-terminal region and a glutamine/proline (Gln/Pro)-rich domain near the 5' end. Two alternative splice sites were described, splice I in the Gln/Pro-rich domain (51 bp) and splice II between ZFs 3 and 4 (9 bp). Using RNA polymerase chain reaction (PCR) we show that Wilms' tumors contain all four possible transcripts, which are also identified in normal adult and embryonic kidney cells. The transcripts containing the 9-bp ZF insert were always predominant in tumors and normal cells. The presence of all four WT1 transcripts in tumors and expressing tissues suggests that each encoded protein isoform has an important role for the function of the WT1 gene.