title: Relationship between the extent of chromosomal losses and the pattern of CpG methylation in gastric carcinomas.
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.
authors.affiliation: Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Hong
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Young-Deok
authors.initials: YD
authors.lastname: Choi
authors.forename: Ki-Ouk
authors.initials: KO
authors.lastname: Min
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Choi
authors.forename: Mun-Gan
authors.initials: MG
authors.lastname: Rhyu
mesh_terms: D002869:Chromosome Aberrations / Q000706:statistics & numerical data*; D002874:Chromosome Mapping / Q000379:methods*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis / Q000379:methods; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D015994:Incidence; D007723:Korea / Q000453:epidemiology; D018895:Microsatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013223:Statistics as Topic; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics*