Germline mutational analysis of CDH1 and pathologic features in familial cancer syndrome with diffuse gastric cancer/breast cancer proband in a Chinese family

Eur J Surg Oncol. 2004 Jun;30(5):531-5. doi: 10.1016/j.ejso.2004.03.004.

Abstract

Aims: Hereditary non-polyposis colorectal cancer, thyroid medullary carcinoma, breast/ovarian cancer and gastric cancer/breast cancer syndrome are encountered in surgery. Some gastric cancer/breast cancer syndrome may be the result of a CDH1 germline mutation. This is the first report of CDH1 germline mutations gastric cancer/breast cancer syndrome in Chinese patients.

Methods: Peripheral blood from the proband, as well as, her first and second degree relatives was collected and CDH1 gene exon 1-16 mutations were screened. E-cadherin/beta-catenin proteins expression and histopathologic features were examined on gastric cancer/breast cancer tissues from the proband.

Results: A C-->T nucleotide substitution at exon 13 (mRNA 2200 locus, Accession number NM-004360) was found. This was a transition from GCC-->GCT in DNA sequence (Ala154Ala). Diffuse-type gastric cancer and infiltrating ductal breast carcinoma were present. Both tumours preserved E-cadherin/beta-catenin expression immunohistochemically.

Conclusions: Familial cancer syndrome with diffuse-type gastric cancer/breast cancer proband in Chinese has a propensity of early onset during lifespan. No truncating or splice-site CDH1 mutations had been identified in this family. A silent nucleotide variation in exon 13 of the CDH1 gene may contribute to some forms of cancer susceptibility.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Substitution / genetics
  • Asian People / genetics*
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cadherins / metabolism
  • Carbohydrate Dehydrogenases / genetics*
  • Carcinoma, Ductal / genetics*
  • Carcinoma, Ductal / metabolism
  • Carcinoma, Ductal / pathology*
  • China
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Cytoskeletal Proteins / metabolism
  • DNA, Neoplasm / genetics
  • Exons / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Germ-Line Mutation / genetics*
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Syndrome
  • Trans-Activators / metabolism
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • DNA, Neoplasm
  • Trans-Activators
  • beta Catenin
  • Carbohydrate Dehydrogenases
  • cellobiose-quinone oxidoreductase