Topic Completed: 1 November 2015

Minor changes: 31 August 2020

Copyright: 2002-2020,, Inc.

PubMed Search: FHIT [title]

Sheren Younes, M.D.
Page views in 2019: 3
Page views in 2020 to date: 7
Cite this page: Younes S. FHIT. website. Accessed September 20th, 2020.
Definition / general
  • Fragile histidine triad (FHIT) gene, which is partially or entirely lost in most human cancers
  • FHIT is a 17 kd protein containing 147 amino acids; FHIT protein is phosphorylated at tyrosine 114 by Src family proteins (Lancet Oncol 2002;3:748)
  • Tumor suppressor gene is present at FRA3B, one of the most common fragile sites (Nat Rev Cancer 2001;1:214)
  • Common Fragile Sites (CFSs) are non-randomly distributed specific loci
  • Under conditions that impair DNA replication, CFSs show breaks, gaps and rearrangements, making cells susceptible to genomic instability
  • Genetic alterations of FHIT include deletions, translocations and promoter hypermethylation that results in loss or reduction of FHIT protein expression
  • Loss of one allele result in reduction of FHIT in metaplastic lesions, and loss of both alleles is associated with loss of FHIT expression (Annu Rev Genet 1998;32:7)
Clinical features
  • Lung cancer
    • FHIT loss is associated with invasiveness in lung tumor cells (Oncogene 2010;29:1203), due to expression of genes associated with epithelial mesenchymal transition (PLoS One 2013;8:e78610)
    • FHIT loss correlates with shorter overall survival, relapse free survival and poor response to cisplatin-based chemotherapy in non small cell lung carcinoma (Oncogene 2015;34:2505), and FHIT methylation is a useful biomarker of biologically aggressive disease in these patients (Asian Pac J Cancer Prev 2014;15:4281)
  • FHIT knockout mice:
    • Are much more susceptible to cancer induction than wild type mice (Proc Natl Acad Sci U S A 2000;97:4742)
    • FHIT viral gene therapy in mouse cancer cell models reverses carcinogen-induced tumors (Nat Rev Cancer 2001;1:214)
    • Similarly, overexpression of FHIT in FHIT negative cancer cell lines leads to suppression of tumorigenicity
  • Squamous cell carcinoma: FHIT loss by immunohistochemistry is related to higher grade, poor overall survival and disease progression in patients treated with chemotherapy (Appl Immunohistochem Mol Morphol 2014;22:275)
  • Urothelial carcinoma: FHIT is immunohistochemically expressed at lower level compared to adjacent normal bladder
    • Expression is related to advanced stage, lower grade, large tumor size, tumor recurrence and reduced survival (J Int Med Res 2012;40:507)
  • Nasopharyngeal carcinoma: LOH and abnormal FHIT expression correlate with advanced clinical stage and recurrence (Eur Arch Otorhinolaryngol 2010;267:1933)
  • Glioblastoma: reduction or loss of FHIT protein expression by genetic alteration or epigenetic mechanism may be associated with tumorigenesis (Cell Mol Neurobiol 2010;30:301)
Back to top
Image 01 Image 02