E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer

To extend earlier observations of germline E-cadherin mutations in kindreds with an inherited susceptibility to diffuse gastric cancer, we searched fo r germline E-cadherin mutations in five further families affected predomina ntly by diffuse gastric cancer and one family with a history of diffuse gas tric cancer and early-onset breast cancer. Heterozygous inactivating mutati ons were found in the E-cadherin gene in each of these families. No mutatio n hotspots were identified. These results demonstrate that germline mutatio n of the E-cadherin gene is a common cause of hereditary diffuse gastric ca ncer and suggest a role for these mutations in the incidence of breast canc er. Hum Mutat 14:249-255, 1999. (C) 1999 Wiley-Liss, Inc.