Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients.
BACKGROUND
Germline mono-allelic promoter hypermethylation of the MLH1 or MSH2 gene in families with hereditary nonpolyposis colorectal cancer has recently been reported. The purpose of this study was to evaluate if germline promoter hypermethylation of the tumor suppressor gene CDH1 (E-cadherin) might cause predisposition to gastric cancer.


METHODS
We prepared two groups of samples, a group of blood samples from 22 patients with familial gastric cancer or early-onset gastric cancer selected from among 39 patients, and a group of non-cancerous gastric tissue samples from 18 patients with sporadic gastric cancer showing loss of CDH1 expression selected from among 159 patients. We then investigated the allele-specific methylation status of the CDH1 promoter by bisulfite sequencing of multiple clones.


RESULTS
Although there was a difference between the methylation level of the two alleles in some samples, there was no mono-allelic promoter hypermethylation in any of the samples.


CONCLUSIONS
These results suggest that germline mono-allelic hypermethylation of the CDH1 promoter is not a major predisposing factor for gastric cancer.
Yamada
Hidetaka
H
First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan. h-yamada@akiha.hama-med.ac.jp
Shinmura
Kazuya
K
Goto
Masanori
M
Iwaizumi
Moriya
M
Konno
Hiroyuki
H
Kataoka
Hideki
H
Yamada
Masami
M
Ozawa
Takachika
T
Tsuneyoshi
Toshihiro
T
Tanioka
Fumihiko
F
Sugimura
Haruhiko
H
D015703:Antigens, CD; D015820:Cadherins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D019175:DNA Methylation; D015870:Gene Expression; D005787:Gene Frequency; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D018922:HL-60 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics*
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D012333:RNA, Messenger