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DNA aberrations at the retinoblastoma gene locus in human squamous cell carcinomas of the lung
R Sachse1, Y Murakami, M Shiraishi
1Oncogene Division, National Cancer Center Research Institute, Tokyo, Japan.
Abstract:
We detected DNA aberrations at the RB locus in surgical specimens of human primary non-small cell lung carcinoma by single-strand conformation polymorphism analysis of polymerase chain reaction products amplified from regions of exons 2 to 27 including parts of the flanking intron sequences. Detection of nucleotide sequence polymorphism revealed loss of heterozygosity in six of eight informative cases among 13 squamous cell carcinomas analysed. In two of the six cases, mutations in the remaining allele were detected. In 25 adenocarcinomas analysed, no loss of heterozygosity was observed in 16 informative cases and a point mutation was detected in one of the uninformative cases. In one of three adenosquamous carcinomas analysed, a point mutation was detected and one adenoid cystic carcinoma analysed showed allelic loss of the RB gene. Our results indicated that loss of heterozygosity at the RB locus is frequent in squamous cell carcinomas of the lung, but not in adenocarcinomas. In the squamous cell carcinomas with allelic loss, mutations of the RB gene in the remaining alleles were found in one third of the tumors.
Insights
DNA aberrations at the RB locus are frequent in squamous cell lung carcinomas but not adenocarcinomas. Mutations in the remaining RB allele were found in one third of squamous cell tumors with allelic loss.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung carcinoma (NSCLC) is a major cause of cancer mortality.
- The Retinoblastoma (RB) gene is a critical tumor suppressor gene.
- Alterations in tumor suppressor genes are common in cancer development.
Purpose of the Study:
- To investigate DNA aberrations at the RB locus in human primary non-small cell lung carcinoma.
- To determine the frequency of RB gene alterations in different subtypes of NSCLC.
Main Methods:
- Single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products.
- Analysis of exons 2 to 27 and flanking intron sequences of the RB gene.
- Detection of nucleotide sequence polymorphism, loss of heterozygosity (LOH), and point mutations.
Main Results:
- Loss of heterozygosity at the RB locus was detected in 6 of 8 informative squamous cell carcinomas (SCC).
- Mutations in the remaining RB allele were found in 2 of 6 SCC cases with LOH.
- No LOH was observed in 16 informative adenocarcinomas; one point mutation was detected.
- One adenosquamous carcinoma showed a point mutation, and one adenoid cystic carcinoma showed allelic loss of the RB gene.
Conclusions:
- Loss of heterozygosity at the RB locus is frequent in squamous cell lung carcinomas.
- RB gene alterations are less common in adenocarcinomas of the lung.
- These findings highlight the importance of the RB gene in the pathogenesis of specific NSCLC subtypes.