Concurrent hypermethylation of multiple tumor-related genes in gastric carcinoma and adjacent normal tissues.
BACKGROUND
Transcriptional silencing by CpG-island hypermethylation now is believed to be an important mechanism of tumorigenesis. To date, studies on CpG-island hypermethylation in gastric carcinoma and adjacent normal tissues are few.


METHODS
The authors examined 5 gastric carcinoma cell lines, 26 frozen gastric carcinoma tissues and their adjacent nontumor area for concurrent CpG-island hypermethylation in 6 tumor-related genes (p15, p16, E-cadherin, GST-pi, hMLH1, and VHL) by methylation-specific polymerase chain reaction. Nontumorous gastric tissues from 10 gastritis patients were used as controls.


RESULTS
Hypermethylation was not detected in any tissue taken from gastritis patients but was identified in all 5 cell lines and in 24 (92.3%) gastric carcinoma patients. CpG-island methylation in tumor-related genes also was detected in 7 out of the 25 adjacent normal tissues from cancer patients. Hypermethylation of E-cadherin, p15, and p16 were detected more frequently than GST-pi and hMLH1, whereas aberrant methylation of VHL was not detected. Concurrent hypermethylation in 2 or more tumor-related genes was detected in 3 out of the 5 gastric carcinoma cell lines, 22 (84.6%) tumor samples, and 5 (20%) adjacent gastric tissues. Eighteen (69.2%) tumor samples showed hypermethylation in >or= 3 genes.


CONCLUSIONS
The current study showed that concurrent hypermethylation of multiple tumor-related genes is detected frequently in gastric carcinoma and adjacent normal tissues. Study findings suggested that a mechanism that leads to dysregulation in CpG-island methylation is likely to be involved in the early gastric carcinogenesis process.
Leung
W K
WK
Department of Medicine & Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR. wkleung@cuhk.edu.hk
Yu
J
J
Ng
E K
EK
To
K F
KF
Ma
P K
PK
Lee
T L
TL
Go
M Y
MY
Chung
S C
SC
Sung
J J
JJ
D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019942:Genes, p16 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008745:Methylation; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; C493966:CDKN2B protein, human; D015820:Cadherins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000070957:MutL Protein Homolog 1