Ile-Leu substitution (I415L) in germline E-cadherin gene (CDH1) in Japanese familial gastric cancer.
BACKGROUND
Germline mutation in the cell adhesion molecule E-cadherin is known to be associated with the development of undifferentiated or diffuse-type familial gastric cancers, but the prevalence of this contribution seems to be low in Japanese familial cases, so far.


METHODS
We screened all exons of the E-cadherin gene for mutations in 101 Japanese patients having an intense family history of gastric cancers.


RESULTS
An abnormal band pattern was found in exon 9 in three patients (Y6, B21, B37) from two families by PCR-SSCP. DNA sequencing analysis of these three patients revealed isoleucine-leucine substitution at codon 415 in exon 9. B21 and B37 are siblings and the other three brothers died of gastric cancer and another brother (B36) has not been affected by gastric cancer to date. This case (B36) did not have this alteration in the exon 9 of E-cadherin.


CONCLUSIONS
Although the mechanistic basis is not clear, our findings may provide a possibility that this additional missense mutation in germline E-cadherin gene may contribute to gastric cancer predisposition.
Wang
Ying
Y
First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Song
Jian-Ping
JP
Ikeda
Masami
M
Shinmura
Kazuya
K
Yokota
Jun
J
Sugimura
Haruhiko
H
D015820:Cadherins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013274:Stomach Neoplasms / Q000235:genetics*
D015820:Cadherins