Relationship between the extent of chromosomal losses and the pattern of CpG methylation in gastric carcinomas

J Korean Med Sci. 2005 Oct;20(5):790-805. doi: 10.3346/jkms.2005.20.5.790.


The extent of unilateral chromosomal losses and the presence of microsatellite instability (MSI) have been classified into high-risk (high- and baseline-level loss) and low-risk (low-level loss and MSI) stem-line genotypes in gastric carcinomas. A unilateral genome-dosage reduction might stimulate compensation mechanism, which maintains the genomic dosage via CpG hypomethylation. A total of 120 tumor sites from 40 gastric carcinomas were examined by chromosomal loss analysis using 40 microsatellite markers on 8 chromosomes and methylation analysis in the 13 CpG (island/non-island) regions near the 10 genes using the bisulfite-modified DNAs. The high-level-loss tumor (four or more losses) showed a tendency toward unmethylation in the Maspin, CAGE, MAGE-A2 and RABGEF1 genes, and the other microsatellite-genotype (three or fewer losses and MSI) toward methylation in the p16, hMLH1, RASSF1A, and Cyclin D2 genes (p<0.05). The non-island CpGs of the p16 and hMLH1 genes were hypomethylated in the high-level-loss and hypermethylated in the non-high-level-loss sites (p<0.05). Consequently, hypomethylation changes were related to a high-level loss, whereas the hypermethylation changes were accompanied by a baseline-level loss, a low-level loss, or a MSI. This indicates that hypomethylation compensates the chromosomal losses in the process of tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Aberrations / statistics & numerical data*
  • Chromosome Mapping / methods*
  • CpG Islands / genetics*
  • DNA Methylation*
  • DNA Mutational Analysis / methods
  • France / epidemiology
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing / methods
  • Genomic Instability / genetics
  • Humans
  • Incidence
  • Korea / epidemiology
  • Microsatellite Repeats / genetics
  • Polymorphism, Genetic
  • Risk Assessment / methods*
  • Risk Factors
  • Statistics as Topic
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / genetics*