Functionally inactivating point mutation in the tumor-suppressor IRF-1 gene identified in human gastric cancer

Int J Cancer. 1998 Aug 12;77(4):522-7. doi: 10.1002/(sici)1097-0215(19980812)77:4<522::aid-ijc8>;2-w.


Loss of heterozygosity (LOH) observed in human tumors strongly suggests the existence of (a) tumor-suppressor gene(s) at the concerned locus. A series of studies has revealed that LOH on the long arm of chromosome 5 (5q) frequently occurs in differentiated gastric adenocarcinomas. Furthermore, it has been shown that the interferon regulatory factor-1 (IRF-1) locus on chromosome 5q31.1 is one of the common minimal regions of LOH in these cancers. IRF-1 is a transcriptional activator that shows tumor-suppressor activity in the mouse. In the present study, we examined the sequence of the IRF-1 gene in 9 cases of histologically differentiated gastric adenocarcinomas, all of which exhibited LOH at the IRF-1 locus. We identified a mis-sense mutation in the residual allele in one case. This mutated form of IRF-1 showed markedly reduced transcriptional activity. In addition, overexpression of wild-type IRF-1 induced cell-cycle arrest, whereas such activity was attenuated in the mutant IRF-1. These results suggest that the loss of functional IRF-1 is critical for the development of human gastric cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Cycle / genetics
  • Chromosomes, Human, Pair 5 / genetics*
  • DNA-Binding Proteins / genetics*
  • Genes, Tumor Suppressor / genetics*
  • Humans
  • Interferon Regulatory Factor-1
  • Loss of Heterozygosity*
  • Mice
  • Phosphoproteins / genetics*
  • Point Mutation*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology


  • DNA-Binding Proteins
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Irf1 protein, mouse
  • Phosphoproteins