Infrequency ofras,p53, WT1, or RB gene alterations in Wilms tumors

Background. Alteration of the ras family of oncogenes and of the tumor suppressor genes p53 and RB are the most common genetic events in human tumors. Although there have been no reports of the prevalence of these alterations in Wilms tumors, overexpression of the N-myc and insulin-like growth factor-II (IGF-II) genes have been observed, and alteration of another tumor suppressor gene (WT1) has been demonstrated. Methods. Forty-four Wilms tumor specimens were tested for the presence of N-, K-, and H-ras mutations in codons 12,13, and 61 by single-strand conformation polymorphism (SSCP) analysis and direct DNA sequence analysis. Sixteen tumors were tested for abnormalities of WT1 by Southern and northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). N-myc, c-myc, WT1, and IGF-II mRNA expression was measured in 16 tumors by Northern blot analysis. Thirty-eight tumors were screened for p53 mutations by SSCP analysis and direct DNA sequence analysis. Nine tumors were analyzed for loss of heterozygosity (LOH) of RB. Results. Although the authors confirmed that N-myc and IGF-II are overexpressed in Wilms tumors, no mutations of ras family, p53, or RB genes were identified, and no gross alterations of WT1 were detected by Southern or Northern blot analysis. Conclusions. These findings suggest that H-ras, K-ras, N-ras, p53, and RB are not involved in the pathogenesis of Wilms tumor.