Relationship between the extent of chromosomal losses and the pattern of CpG methylation in gastric carcinomas.
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.
Hong
Seung-Jin
SJ
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Kim
Young-Ho
YH
Choi
Young-Deok
YD
Min
Ki-Ouk
KO
Choi
Sang-Wook
SW
Rhyu
Mun-Gan
MG
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*