title: Genetics of hereditary diffuse gastric cancer: progress and future challenges.
abstract: Hereditary diffuse gastric cancer (HDGC) is a rare cancer susceptibility syndrome. One third of HDGC syndrome families carry germline mutations of the E-cadherin gene. Owing to the limitation of the current endoscopic screening techniques and since no chemoprevention is yet available, total prophylactic gastrectomy is the only option offered to carriers of inactivating mutations in genetic counseling. In this regard, 30% of the E-cadherin germline mutations reported to date are of the missense type, and since their pathogenic significance is not straightforward, the management of carriers of such mutations is suboptimal. In the absence of definitive clinical evidence, functional in vitro studies together with in silico analysis have been used to infer the pathogenic significance of germline missense mutations. Since most of the HDGC families reported to date are negative for E-cadherin germline mutations, the identification of alternative genes underlying the tumorigenesis of diffuse gastric has become an important target for research.
authors.affiliation: Institute of Molecular Pathology & Immunology of the University of Porto, Rua Dr Roberto Frias S/N 4200-465, Porto, Portugal. gsuriano@ipatimup.pt
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Suriano
authors.forename: Paulo
authors.initials: P
authors.lastname: Ferreira
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Mateus
authors.forename: Joana
authors.initials: J
authors.lastname: Correia
authors.forename: Lara
authors.initials: L
authors.lastname: Henriques
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
mesh_terms: D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics* / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology