Fragile histidine triad (FHIT) gene abnormalities in lung cancer

S. Zöchbauer-Müller, I. I. Wistuba, J. D. Minna, A. F. Gazdar

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)141-145
Number of pages5
JournalClinical lung cancer
Issue number2
StatePublished - Nov 2000


  • Chromosome 3p
  • FHIT
  • FRA3B
  • Lung cancer
  • Tumor-suppressor gene

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research


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