The role of the FHIT/FRA3B locus in cancer

Annu Rev Genet. 1998;32:7-31. doi: 10.1146/annurev.genet.32.1.7.

Abstract

Common fragile sites form gaps at characteristic chromosome bands in metaphases from normal cells after aphidicolin induction. The distribution of common fragile sites parallels the positions of neoplasia-associated chromosomal rearrangements, prompting the proposal that fragility disposes to chromosomal rearrangements. Implicit in this hypothesis is that genes at fragile sites are altered by chromosome rearrangement and thus contribute to neoplastic growth. Chromosome band 3p14.2, encompassing the most inducible common fragile region, FRA3B, has been cloned and the FHIT gene, straddling FRA3B, characterized. The gene is inactivated by deletions in cancer-derived cell lines and primary tumors and Fhit protein is absent or reduced in lung, stomach, kidney, and cervical carcinomas, consistent with function as a tumor suppressor. FRA3B thus fulfills the prophecy that fragile site alterations contribute to the neoplastic process through inactivation of a tumor suppressor gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acid Anhydride Hydrolases*
  • Alleles
  • Amino Acid Sequence
  • Chromosome Fragile Sites
  • Chromosome Fragility*
  • Chromosomes, Human, Pair 3 / genetics*
  • Female
  • Gene Deletion
  • Gene Rearrangement
  • Genes, Tumor Suppressor
  • Homozygote
  • Humans
  • Male
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Neoplasms / genetics*
  • Physical Chromosome Mapping
  • Proteins / genetics
  • Proteins / physiology
  • RNA, Neoplasm / genetics

Substances

  • Neoplasm Proteins
  • Proteins
  • RNA, Neoplasm
  • fragile histidine triad protein
  • Acid Anhydride Hydrolases