English

Abstract

Abstract Introduction Hereditary diffuse gastric cancer is an autosomal inherited syndrome associated with the E-cadherin germline mutations. Different types of CDH1 germline mutations have been reported; the missense alterations are rarely identified when compared with truncating mutations. The identification of missense mutation represents a clinical burden, since its pathogenicity is still under genetic and clinical studies. The aim of this critical review was to discuss E-cadherin germline missense mutations in diffuse gastric cancer. Materials and methods In this paper, we reviewed the literature data about the CDH1 germline missense mutations identified in early-onset and hereditary diffuse gastric tumours. The roles of clinical surveillance and prophylactic gastrectomy were discussed. Mutations reported in breast lobular cancer were excluded. Results We identified a total of 31 CDH1 germline missense mutations with different pathogenic impact on E-cadherin function (pathogenic vs. neutral). The majority of these alterations were localized at the extracellular domain of the CDH1 gene. These mutations affected indifferently hereditary and sporadic diffuse gastric carcinomas. Conclusion In this critical review, we reported all missense mutations identified to date and discussed about the E-cadherin missense mutation function, clinical management for asymptomatic mutation carriers and the roles of prophylactic total gastrectomy and endoscopic surveillance.