Related Experiment Video
Updated: Aug 17, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Fragile histidine triad (FHIT) gene abnormalities in lung cancer
S Zöchbauer-Müller1, I I Wistuba, J D Minna
1Hamon Center for Therapeutic Oncology Research, The University of Texas, Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Abstract:
Lung cancer is the most common cause of cancer death in the world. In recent years, enormous progress has been made in understanding the molecular and cellular biology of lung cancer. The fragile histidine triad (FHIT) gene, a candidate tumor-suppressor gene, was recently identified at chromosome 3p14.2, spanning the FRA3B common fragile site. Frequent allelic losses as well as homozygous deletions have been described at the FHIT locus, making FHIT a strong candidate as a tumor-suppressor gene. However, the occurrence of mutations is very rare. Aberrant FHIT transcripts, including deletions of exons, insertions between exons, and insertions replacing exons, are detected in a high percentage of lung tumors. Reduction or complete loss of FHIT expression by immunohistochemical testing is seen in about 30%-70% of non small-cell lung cancer and in about 20% of bronchial biopsies from chronic smokers without evidence of lung cancer. This finding supports the theory that FHIT is a molecular target of tobacco smoke carcinogens. However, the location of the gene in one of the most fragile sites of the human genome and the paucity of mutations have led to an alternative hypothesis that abnormalities of the gene are bystander effects resulting from disruption of the FRA3B locus. Thus, the function of FHIT as a candidate tumor-suppressor gene is still controversial, and additional studies are necessary to clarify the role of FHIT in lung cancer pathogenesis.
Insights
The fragile histidine triad (FHIT) gene
Area of Science:
- Molecular biology
- Cancer research
- Genetics
Background:
- Lung cancer is a leading cause of cancer mortality worldwide.
- The fragile histidine triad (FHIT) gene, located at chromosome 3p14.2, is a potential tumor suppressor.
- FHIT alterations are frequently observed in lung tumors, but the exact role is debated.
Purpose of the Study:
- To investigate the role of the FHIT gene in lung cancer development.
- To explore the relationship between FHIT alterations and tobacco smoke exposure.
- To clarify the controversial function of FHIT as a tumor suppressor.
Main Methods:
- Analysis of FHIT gene alterations (allelic losses, homozygous deletions, aberrant transcripts) in lung tumors.
- Immunohistochemical assessment of FHIT protein expression in non-small cell lung cancer and bronchial biopsies from smokers.
- Comparison of mutation data with FHIT expression levels.
Main Results:
- While FHIT mutations are rare, aberrant FHIT transcripts are common in lung tumors.
- Reduced or lost FHIT expression is observed in 30-70% of non-small cell lung cancer and 20% of chronic smokers.
- These findings suggest FHIT may be a target of tobacco carcinogens, but its role is complex.
Conclusions:
- The function of FHIT as a tumor suppressor in lung cancer remains controversial.
- Aberrant FHIT transcripts and reduced expression are prevalent, potentially linked to tobacco smoke.
- Further research is needed to elucidate FHIT's precise role in lung cancer pathogenesis due to its location at a fragile site and rare mutations.
Related Concept Videos
02:30Histone Variants at the Centromere
02:39lncRNA - Long Non-coding RNAs