E-cadherin gene variants in gastric cancer families whose probands are diagnosed with diffuse gastric cancer

Tomonori Yabuta, Kazuya Shinmura, Masachika Tani, Satoru Yamaguchi, Kimio Yoshimura, Hitoshi Katai, Takashi Nakajima, Erito Mochiki, Toshimasa Tsujinaka, Motohisa Takami, Kazuo Hirose, Akio Yamaguchi, Seiichi Takenoshita, Jun Yokota

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81 Citations (Scopus)


To identify germline E-cadherin mutations responsible for the predisposition to diffuse gastric cancer (DGC) among the Japanese, we screened 17 patients with familial aggregation of gastric cancer by sequencing analysis. All the patients were diagnosed with DGC and had at least 1 sibling with gastric cancer. Two novel E-cadherin gene variants were detected. One was detected in 1 patient only and associated with an amino acid substitution (Val/Met) at codon 832 in the region essential for binding to β-catenin. The M832 variant was detected not only in the proband but also in 2 other gastric cancer patients in the family. Immunohistochemical analysis of gastric cancer tissue from the proband revealed that E-cadherin expression was markedly reduced and β-catenin expression was also reduced in cancer cells. However, no significant difference in the activity of β-catenin binding was detected between the M832 variant and V832 wild-type E-cadherin in immunofluorescence and immunoprecipitation/Western blot analyses. The other was detected in 5 patients and was located in the splice donor site (IVSI+6T/ C); however, RT-PCR analysis indicated that the IVS+6C variant did not cause an aberrant splicing. Thus, the M832 variant could be a germline mutation causative of familial aggregation of DGC, although further functional studies are needed to understand the pathogenic significance of this variant.

Original languageEnglish
Pages (from-to)434-441
Number of pages8
JournalInternational Journal of Cancer
Issue number5
Publication statusPublished - 2002 Oct 10
Externally publishedYes


  • Diffuse gastric cancer
  • E-cadherin
  • Familial gastric cancer
  • Germline mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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