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Ras oncogene mutations in basal cell carcinomas and squamous cell carcinomas of human skin
J G van der Schroeff1, L M Evers, A J Boot
1Department of Dermatology, University Hospital Leiden, The Netherlands.
Abstract:
Activated ras oncogenes have been detected in a variety of human malignancies. Activation of ras oncogenes usually occurs by point mutations within specific codons of the H-ras, N-ras, and K-ras genes. For the present study, DNA was isolated from 30 basal cell carcinomas (BCC) and 12 squamous cell carcinomas (SCC). After amplification of genomic DNA by using the polymerase chain reaction, the occurrence of point mutations was investigated with 32P-labeled synthetic oligonucleotides. These probes are complementary to the known point-mutated nucleotide sequences of the ras genes. In four out of the 30 BCC studied, point mutations were detected at codon 12 of the K-ras gene and at codon 61 of the H-ras gene. The K-ras mutations involve glycine to cysteine and glycine to asparagine amino acid changes. The mutation at codon 61 of the H-ras gene is consistent with a replacement of glutamine by histidine. In one SCC, a point mutation was detected at codon 12 of the K-ras gene, involving a glycine to cysteine substitution in the gene product. These findings demonstrate that mutational activation of ras genes takes place in skin carcinomas, but the rate at which these mutations occur seems to be relatively low.
Insights
Ras gene mutations are found in skin cancers like basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). These oncogene activations occur at low rates in these malignancies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ras oncogenes are frequently activated in human cancers.
- Activation typically results from point mutations in H-ras, N-ras, and K-ras genes.
Purpose of the Study:
- To investigate the presence and types of ras gene point mutations in basal cell carcinomas (BCC) and squamous cell carcinomas (SCC).
Main Methods:
- DNA was extracted from 30 BCC and 12 SCC samples.
- Polymerase chain reaction (PCR) amplified specific ras gene regions.
- 32P-labeled oligonucleotide probes identified point mutations at specific codons.
Main Results:
- Point mutations in ras genes were detected in 4 out of 30 BCCs.
- Mutations occurred at K-ras codon 12 (glycine to cysteine/asparagine) and H-ras codon 61 (glutamine to histidine).
- One SCC sample showed a K-ras codon 12 mutation (glycine to cysteine).
Conclusions:
- Mutational activation of ras genes occurs in skin carcinomas.
- The frequency of these ras gene mutations appears to be low in BCC and SCC.