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Molecular analysis of the FHIT gene at 3p14.2 in lung cancer cell lines
K Yanagisawa1, M Kondo, H Osada
1Department of Internal Medicine II, Nagoya University School of Medicine, Tsurumai-cho, Showa-ku, Japan.
Abstract:
Chromosome 3p is frequently deleted in various cancers including examples in the lung. A novel gene, termed FHIT, was recently isolated from the fragile site at 3p14.2, with aberrant transcripts being reported in lung cancer tumor specimens. To avoid overlooking tumor-specific altered transcripts due to contaminating normal cells in primary tumors, FHIT alterations were examined in 41 lung cancer cell lines in the present study. Lack of detectable expression or exclusive expression of aberrantly spliced transcripts, often accompanied by intragenic homozygous deletions, were observed in 7 of 24 non-small cell lung cancers (29%) but in 0 of 17 small cell lung cancers (0%). Extensive reverse transcription-PCR-single-strand conformation polymorphism analysis revealed polymorphisms and alternative splicing but failed to identify point mutations. These results suggest distinct mechanisms for FHIT alterations in lung tumorigenesis and that further studies of this interesting gene are warranted.
Insights
The FHIT gene, located at chromosome 3p14.2, shows alterations in 29% of non-small cell lung cancer cell lines. These changes, including deletions and aberrant splicing, were not found in small cell lung cancers, suggesting distinct lung cancer mechanisms.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromosome 3p deletions are common in various cancers, including lung cancer.
- A novel gene, FHIT (Fragile Histidine Triad), was identified at the 3p14.2 fragile site.
- Aberrant FHIT transcripts have been previously reported in lung cancer specimens.
Purpose of the Study:
- To investigate FHIT gene alterations in lung cancer cell lines to avoid contamination from normal cells.
- To characterize the specific types of FHIT alterations in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).
Main Methods:
- Analysis of 41 lung cancer cell lines (24 NSCLC, 17 SCLC).
- Utilized reverse transcription-PCR-single-strand conformation polymorphism (RT-PCR-SSCP) analysis.
- Examined FHIT transcript expression, splicing, and intragenic homozygous deletions.
Main Results:
- FHIT alterations, including lack of expression or aberrant splicing, were found in 7 of 24 (29%) NSCLC cell lines.
- Intragenic homozygous deletions accompanied FHIT alterations in some NSCLC cases.
- No FHIT alterations were detected in any of the 17 SCLC cell lines.
- RT-PCR-SSCP identified polymorphisms and alternative splicing but no point mutations in FHIT.
Conclusions:
- Distinct mechanisms underlie FHIT alterations in lung tumorigenesis between NSCLC and SCLC.
- Further research into the FHIT gene's role in lung cancer development is warranted.