Relationship Between the Extent of Chromosomal Losses and the Pattern of CpG Methylation in Gastric Carcinomas.
10.3346/jkms.2005.20.5.790
- Author:
Seung Jin HONG
1
;
Young Ho KIM
;
Young Deok CHOI
;
Ki Ouk MIN
;
Sang Wook CHOI
;
Mun Gan RHYU
Author Information
1. Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea. rhyumung@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Chromosomal Loss;
Aneuploidy;
CpG Methylation;
DNA Methylation;
Dosage Compensation (Genetics);
Stomach Neoplasms;
Prognostic Genotype;
Genetic Phenomena
- MeSH:
Chromosome Aberrations/*statistics and numerical data;
Chromosome Mapping/*methods;
CpG Islands/*genetics;
*DNA Methylation;
DNA Mutational Analysis/methods;
France/epidemiology;
Genetic Predisposition to Disease/epidemiology/genetics;
Genetic Screening/methods;
Genomic Instability/genetics;
Humans;
Incidence;
Korea/epidemiology;
Microsatellite Repeats/genetics;
Polymorphism, Genetic;
Research Support, Non-U.S. Gov't;
Risk Assessment/*methods;
Risk Factors;
Statistics;
Stomach Neoplasms/*enzymology/*genetics
- From:Journal of Korean Medical Science
2005;20(5):790-805
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
