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. Conclusion. 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.