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FRA3B and other common fragile sites: the weakest links

K Huebner1, C M Croce

  • 1Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA. K_Huebner@lac.jci.tju.edu

Nature Reviews. Cancer
|March 21, 2002
PubMed

Insights

The fragile histidine triad (FHIT) gene, located at a fragile site, is lost in most cancers, suggesting it acts as a tumor suppressor. Its inactivation may initiate cancer through a one-hit mechanism.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • The first chromosome alteration linked to familial cancer was identified in 1979.
  • A fragile site was subsequently discovered in the same chromosomal region five years later.
  • The fragile histidine triad (FHIT) gene, spanning this fragile site, is frequently lost in human cancers.

Purpose of the Study:

  • To investigate the tumor-suppressor role of the FHIT gene.
  • To explore the mechanism of tumorigenesis involving FHIT.
  • To determine if genes at other fragile sites are also tumor suppressors.

Main Methods:

  • Analysis of chromosome alterations and fragile sites.
  • Gene expression studies focusing on FHIT.
  • Tumorigenesis pathway investigation.

Main Results:

  • Loss of FHIT gene product in most human cancers indicates a tumor-suppressor function.
  • Inactivation of a single FHIT allele impairs suppressor function, suggesting a 'one-hit' tumorigenesis mechanism.
  • FHIT gene is located at a chromosomal fragile site.

Conclusions:

  • The FHIT gene functions as a tumor suppressor.
  • A 'one-hit' mechanism may drive tumorigenesis due to FHIT inactivation.
  • Further research is needed to identify other tumor suppressor genes at fragile sites.

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