Analysis for microsatellite instability and mutations of the DNA mismatch repair gene hMLH1 in familial gastric cancer

Int J Cancer. 1996 Nov 27;68(5):571-6. doi: 10.1002/(SICI)1097-0215(19961127)68:5<571::AID-IJC3>3.0.CO;2-W.


We examined 30 gastric-cancer patients with a varying degree of family history of stomach cancer and/or synchronous gastric tumors for microsatellite instability. We observed microsatellite instability at at least 1 of 8 loci tested in tumors of 14/30 patients; of these 14, 8 had single locus alterations and 6 had alterations at at least half of the 8 loci. Among the patients with microsatellite instability at > or = 4 loci, 3 patients showed a strong familial clustering of gastric cancer. Mutation analysis of the DNA mismatch repair gene hMLHl on paired non-tumorous and tumor DNA from 10 patients, 6 with microsatellite instability at > or = 4 loci and 4 with an alteration at one locus, revealed a novel missense mutation, present in the normal and tumor DNA of one patient with microsatellite instability at multiple loci in his tumor. His family history of cancer included one second-degree relative affected with gastric cancer. These data suggest that germline mutations in the hMLHl gene occur in some gastric-cancer patients and that in the majority of cases microsatellite instability in gastric tumors may be due to defects in other genes responsible for DNA replication fidelity than the hMLHl.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Aged, 80 and over
  • Carrier Proteins
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Microsatellite Repeats / genetics*
  • Middle Aged
  • MutL Protein Homolog 1
  • Mutation
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins
  • Pedigree
  • Stomach Neoplasms / genetics*


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • MutL Protein Homolog 1