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Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an immune response in squamous
1Department of Human Genetics, Medical School, University of Saarland, Homburg/Saar, Germany.
Abstract:
Amplification of cellular oncogenes is an important mechanism of altered gene expression in human cancers. Using comparative genomic hybridization we recently identified an amplification at 3q26.1-q26.3 in 30% of squamous cell carcinomas of the lung. A variety of methods including microdissection-mediated procedures permit cloning of genes encoded within amplified domains but do not directly lead to the identification of biologically relevant genes. In this study, we have circumvented this problem by combining an immunological and molecular genetic approach to analyze squamous cell lung carcinoma. To identify both amplified and tumor relevant genes, we generated a cDNA expression library from a tumor with the 3q amplification and hybridized the expressed recombinant polypeptides with the autologous serum. Of 400000 cDNA clones we identified 17 antigens which induce an immune response in a patient with squamous cell lung carcinoma. While most clones represent individual genes sequence analysis revealed that four of the 17 cDNAs are nearly identical with the eukaryotic translation initiation factor (eIF)-4gamma recently assigned on 3q. We demonstrated that the gene for eIF-4gamma was amplified within 3q26-q27 in independent squamous cell lung carcinomas. In this study, we report the identification of several antigens which elicit an immune response in a squamous cell lung carcinoma patient including eIF-4gamma. eIF-4gamma is encoded by an amplified gene and possibly plays a crucial part in the development of squamous cell lung carcinoma.
Insights
Researchers identified eukaryotic translation initiation factor 4 gamma (eIF-4γ) as a key antigen in lung cancer. This protein is encoded by an amplified gene and may play a crucial role in squamous cell lung carcinoma development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gene amplification is a key mechanism in human cancer development.
- Amplification at 3q26.1-q26.3 is found in 30% of lung squamous cell carcinomas.
- Identifying specific amplified genes and their roles is challenging.
Purpose of the Study:
- To identify amplified and tumor-relevant genes in lung squamous cell carcinoma.
- To combine immunological and molecular genetic approaches for gene discovery.
- To investigate the role of eukaryotic translation initiation factor 4 gamma (eIF-4γ) in lung cancer.
Main Methods:
- Comparative genomic hybridization (CGH) to identify gene amplifications.
- Construction of a cDNA expression library from tumor tissue.
- Immunization screening using autologous serum to detect tumor antigens.
- Sequence analysis of identified cDNA clones.
- Confirmation of gene amplification in independent tumor samples.
Main Results:
- 17 antigens eliciting an immune response were identified from 400,000 cDNA clones.
- Four of the identified cDNAs were nearly identical to eukaryotic translation initiation factor 4 gamma (eIF-4γ).
- The gene encoding eIF-4γ was confirmed to be amplified in 3q26-q27 in independent lung squamous cell carcinomas.
- eIF-4γ was identified as an antigen recognized by the patient's immune system.
Conclusions:
- eIF-4γ is an amplified gene in lung squamous cell carcinoma.
- eIF-4γ is a tumor antigen that elicits an immune response.
- eIF-4γ may play a significant role in the pathogenesis of squamous cell lung carcinoma.