[Associations of E-cadherin gene (CDH1) and hereditary gastric cancer in China].
OBJECTIVE
To investigate the protein expression, methylation promoter, somatic and germ-line mutations of E-cadherin gene (CDH1) in hereditary gastric cancer in China and to investigate its possible roles.


METHODS
Eight probands diagnosed with ICG-HGC criterion were enrolled in our database from June 1994 to October 2007. Tumor tissues were detected for CDH1 expression by using immunohistochemistry (IHC) methods. CDH1 DNA sequencing was performed for all its 16 exons both in tumor and normal tissues of the same patients to detect somatic and germ-line mutations. Methylation promoter study was performed by using specific primers and polymerase chain reaction (PCR) methods.


RESULTS
IHC analysis confirmed that the CDH1 expression was negative in 7 probands and downregulated in the other on proband. Six mutations in five probands were found with DNA sequencing: two silent mutations and four missense mutations. All six mutations were absent in normal tissues, thereby excluded its presence in germ-line cells. Both DNA missense mutations and gene silencing through promoter methylation was found in 4 probands. Two probands has only promoter methylation and one proband had only silent mutation. No DNA missense mutations or promoter methylation was found in one proband.


CONCLUSIONS
CDH1 gene germ-line mutations are relatively rare in hereditary gastric cancer in China, and whereas CDH1 somatic mutations and promoter methylation synergistically induce CDH1 downregulation in these patients.
Department of Gastrointestinopancreatic Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Wu
W
Song
Yu-long
YL
He
Chang-hua
CH
Zhang
Shi-rong
SR
Cai
Xue-fu
XF
Zhou
Jian-jun
JJ
Peng
Zhao
Z
Wang
Dong-jie
DJ
Yang
Wen-hua
WH
Zhan
D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018095:Germ-Line Mutation; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins