Distinct methylation pattern and microsatellite instability in sporadic gastric cancer

Int J Cancer. 1999 Oct 29;83(3):309-13. doi: 10.1002/(sici)1097-0215(19991029)83:3<309::aid-ijc4>3.0.co;2-z.


Aberrant 5' CpG island methylation is an alternative mechanism of gene inactivation during the development of cancer as demonstrated for several tumor-suppressor genes. Also, marked relationship of microsatellite instability (MSI) and DNA methylation has been reported in sporadic colorectal cancer, which is a result of epigenetic inactivation of hMLH1 in association of promoter hypermethylation. In the present study, we investigated the 5' CpG island hypermethylation of hMLH1, E-cadherin and p16 in 61 primary gastric cancers (GCs) by using combined bisulfite restriction analysis (COBRA) and methylation-specific PCR (MSP), and their MSI status. Of 61 GCs investigated, 5 (8.1%) tumors presented hMLH1 methylation, 16 (26.2%) and 25 (40.9%) showed E-cadherin and p16 methylation respectively, and 8 (13.1%) presented high-frequency MSI (MSI-H). Of the 8 MSI-H patients, 5 presented hMLH1 methylation, whereas no low-frequency MSI (MSI-L) and microsatellite stable (MSS) cases exhibited hMLH1 methylation (5/8 vs. 0/43, p < 0.00001). Furthermore, these patients also presented E-cadherin and p16 hypermethylation. Our data showed a significant correlation between hMLH1 methylation and MSI in GC, and suggested that a common mechanism of aberrant de novo methylation can be postulated in these cancers.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Cadherins / genetics
  • Carrier Proteins
  • CpG Islands
  • DNA Methylation*
  • Genes, Tumor Suppressor*
  • Genes, p16
  • Humans
  • Microsatellite Repeats*
  • MutL Protein Homolog 1
  • Neoplasm Proteins / genetics
  • Nuclear Proteins
  • Stomach Neoplasms / genetics*
  • Tumor Cells, Cultured


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