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

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/β-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/β-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.