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.