Detection of a novel truncated WT1 transcript in human neoplasia

Background: The Wilms' tumor 1 (T1) gene encodes a transcription factor cri tical in urogenital development. Using a new model of prostate cancer progr ession that permits comparison of the cellular and molecular properties of increasingly aggressive sublines of simian virus 40 large T-antigen-immorta lized human prostate epithelial cells within the same lineage, the role of WT1 in tumorigenesis was investigated. Methods and Results: Using RT-PCR and northern blotting, we identified a no vel truncated WT1 transcript in these prostate cancer cell lines. This 2.1- kb transcript consisted of the coding region of the zinc-finger domain of W T1, together with a portion of intron 5 at the 5' end of the transcript. Fu rthermore, two peptides were detected by western blotting using antibodies to epitopes of the COOH terminus of WT1. Using RT-PCR, the 2.1-kb transcrip t was also detected in leukemia cell line K562, breast cancer cell line MCF 7, and blood samples from patients with acute leukemia. Conclusion: These novel findings in both cell lines and patient-derived spe cimens suggest this new WT1 gene alteration has a potential role in the dev elopment of new diagnostic assays for some human malignancies.