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Activated H-ras oncogenes in human kidney tumors
1Institute for Cancer Research, Osaka University Medical School, Japan.
Abstract:
Two H-ras oncogenes were detected by NIH/3T3 transfection assay out of 16 primary kidney tumors, 15 renal cell carcinomas (RCC), and one transitional cell carcinoma in 16 patients. Analysis of ras Mr 21,000 protein suggested single point mutations within codon 12 and 61 in each case. The restriction endonuclease analysis of H-ras gene at codon 12 confirmed this in one of them, and the remaining 15 tumors did not have a mutation at this site. DNAs from the noncancerous portions of the kidney with codon 12 mutated tumor, but not leukocytes from the same patient, showed an abnormal resistance to the endonucleases MspI and HpaII, suggesting a presence of codon 12 mutated H-ras gene in the noncancerous cells. No amplification of ras genes was detected in the 16 tumors analyzed. In one of eight tumors from patients heterozygous for H-ras related BamHI restriction fragments, one allele was lost in the tumor but not in the noncancerous portion of the same kidney. Although cytogenetic studies have previously suggested nonrandom involvement of c-raf-1 gene in RCC, no abnormality in the size nor amount of raf transcript was detected in the 15 RCCs. Our results thus indicated that the genetic lesions affecting ras genes do occur in human RCC, and probably serve as one of multisteps in the carcinogenic process.
Insights
Genetic mutations in H-ras oncogenes were found in kidney tumors, including renal cell carcinoma (RCC). These ras gene alterations likely contribute to kidney cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Renal cell carcinoma (RCC) is a significant human malignancy.
- The role of oncogenes, such as H-ras, in RCC pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the presence and nature of H-ras oncogene mutations in primary kidney tumors, including RCC.
- To explore the potential involvement of H-ras gene alterations in the multistep process of kidney cancer development.
Main Methods:
- NIH/3T3 transfection assay to detect H-ras oncogenes in 16 primary kidney tumors.
- Analysis of ras p21 protein for point mutations at codons 12 and 61.
- Restriction endonuclease analysis (MspI, HpaII, BamHI) to confirm mutations and assess gene status.
- Cytogenetic and transcript analysis for c-raf-1 gene.
Main Results:
- Two H-ras oncogenes were detected in 16 kidney tumors (15 RCCs, 1 transitional cell carcinoma).
- Point mutations in codons 12 and 61 of the H-ras gene were identified.
- Evidence suggests the presence of a codon 12 mutated H-ras gene in noncancerous kidney cells from a patient.
- No ras gene amplification was observed; one case showed allele loss in the tumor.
- No abnormalities in c-raf-1 gene size or amount were detected in RCCs.
Conclusions:
- Genetic lesions affecting ras genes occur in human renal cell carcinoma.
- These ras gene alterations are likely involved in the multistep carcinogenic process of kidney cancer.
- Further research into oncogene roles in RCC is warranted.