Wilms tumor 1 expression in malignant gliomas and correlation of +KTS isoforms with p53 status

OBJECT The WT1 gene is overexpressed in many types of human cancer. It has been demonstrated that Wilms tumor 1 (WT1) promotes tumor cell proliferation and survival in some cell lines by inhibiting p53-mediated apoptosis; however, this relationship has not been investigated in gliomas. The goal in this study was to characterize the expression pattern of WT1 in human gliomas and to determine if a correlation exists between WT1 expression and p53 status. METHODS The authors screened nine malignant glioma cell lines, 50 glioblastoma multiforme (GBM) samples, and 16 lower-grade glial tumors for WT1 expression. RESULTS Five of nine cell lines, 44 of 50 GBM samples, and 13 of 16 lower-grade gliomas expressed WT1 mRNA on reverse transcriptase polymerase chain reaction (PCR) analysis. Expression of WT1 was not detected in normal astrocytes. Two WT1 isoforms, +/+ and −/+, were expressed in the majority of these samples. Real-time PCR analysis of the GBM cell lines revealed that the level of WT1 mRNA ranged from 6.33 to 214.70 ng per ng 18S ribosomal RNA. The authors screened the GBM samples for p53 mutation by using PCR and single-stranded conformational polymorphism analysis, and they demonstrated an association between WT1 expression and p53 status. Tumors that contained wild-type p53 were significantly more likely to express WT1 than tumors that contained mutant p53. CONCLUSIONS The presence of WT1 in glioma cell lines and the majority of primary tumor samples and its absence in normal astrocytes support the suggestion that WT1 expression is important in glioma biology.