title: E-cadherin alterations in hereditary disorders with emphasis on hereditary diffuse gastric cancer.
abstract: The only gastric cancer (GC) syndrome with a proven inherited defect is designated as hereditary diffuse gastric cancer (HDGC) and is caused by germline E-cadherin/CDH1 alterations. Other E-cadherin-associated hereditary disorders have been identified, encompassing HDGC families with or without cleft-lip/palate involvement, isolated early-onset diffuse GCs, and lobular breast cancer families without GC. To date, 141 probands harboring more than 100 different germline CDH1 alterations, mainly point mutations and large deletions, have been described in these different settings. A third of all HDGC families described so far carry recurrent CDH1 alterations. Full screening of CDH1 is recommended in patients fulfilling the HDGC criteria and total prophylactic gastrectomy is the only reliable intervention for carriers of pathogenic alterations. In this chapter, we discuss CDH1-associated syndromes, frequency and type of CDH1 germline alterations, clinical criteria, and guidelines for genetic counseling, molecular pathology, and available animal/cell line models of the disease.
authors.affiliation: Expression Regulation in Cancer Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Oliveira
authors.forename: Hugo
authors.initials: H
authors.lastname: Pinheiro
authors.forename: Joana
authors.initials: J
authors.lastname: Figueiredo
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics*; D004195:Disease Models, Animal; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D051379:Mice; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D015820:Cadherins