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Infrequency of ras, p53, WT1, or RB gene alterations in Wilms tumors
1Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.
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.
Insights
Ras family, p53, and RB genes are not mutated in Wilms tumors, indicating they do not play a role in the development of this pediatric cancer. N-myc and IGF-II were found to be overexpressed.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ras family oncogenes, p53, and RB tumor suppressor genes are frequently altered in human cancers.
- Wilms tumors exhibit N-myc and IGF-II gene overexpression and WT1 gene alterations.
- The role of common oncogenes and tumor suppressors in Wilms tumor pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the involvement of ras family genes (H-ras, K-ras, N-ras), p53, and RB in the development of Wilms tumors.
- To analyze mutations and alterations in these key genes within Wilms tumor specimens.
Main Methods:
- Analysis of ras gene mutations (codons 12, 13, 61) using single-strand conformation polymorphism (SSCP) and direct DNA sequencing.
- Assessment of WT1 gene abnormalities via Southern and Northern blot analysis and RT-PCR.
- Screening for p53 mutations and LOH of RB, alongside measurement of N-myc, c-myc, WT1, and IGF-II mRNA expression.
Main Results:
- No mutations were detected in H-ras, K-ras, or N-ras genes.
- No mutations or gross alterations were found in the p53 or RB genes.
- Consistent with prior reports, N-myc and IGF-II were overexpressed, while WT1 alterations were not detected by the methods used.
Conclusions:
- H-ras, K-ras, N-ras, p53, and RB genes are unlikely to be involved in the pathogenesis of Wilms tumor.
- The study highlights that common genetic alterations found in other cancers are not prevalent in Wilms tumors.
- Further research may be needed to elucidate the specific genetic pathways driving Wilms tumor development.
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