title: E-cadherin germline mutation carriers: clinical management and genetic implications.
abstract: Hereditary diffuse gastric cancer is an autosomic dominant syndrome associated with E-cadherin protein (CDH1) gene germline mutations. Clinical criteria for genetic screening were revised in 2010 by the International Gastric Cancer Linkage Consortium at the Cambridge meeting. About 40 % of families fulfilling clinical criteria for this inherited disease present deleterious CDH1 germline mutations. Lobular breast cancer is a neoplastic condition associated with hereditary diffuse gastric cancer syndrome. E-cadherin constitutional mutations have been described in both settings, in gastric and breast cancers. The management of CDH1 asymptomatic mutation carriers requires a multidisciplinary approach; the only life-saving procedure is the prophylactic total gastrectomy after thorough genetic counselling. Several prophylactic gastrectomies have been performed to date; conversely, no prophylactic mastectomies have been described in CDH1 mutant carriers. However, the recent discovery of novel germline alterations in pedigree clustering only for lobular breast cancer opens up a new debate in the management of these individuals. In this critical review, we describe the clinical management of CDH1 germline mutant carriers providing specific recommendations for genetic counselling, clinical criteria, surveillance and/ or prophylactic surgery.
authors.affiliation: Molecular Senology Unit, via G. Ripamonti 435, European Institute of Oncology, 20141, Milan, Italy, giovanni.corso@ieo.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corso
authors.forename: Joana
authors.initials: J
authors.lastname: Figueiredo
authors.forename: Roberto
authors.initials: R
authors.lastname: Biffi
authors.forename: Chiara
authors.initials: C
authors.lastname: Trentin
authors.forename: Bernardo
authors.initials: B
authors.lastname: Bonanni
authors.forename: Irene
authors.initials: I
authors.lastname: Feroce
authors.forename: Davide
authors.initials: D
authors.lastname: Serrano
authors.forename: Enrico
authors.initials: E
authors.lastname: Cassano
authors.forename: Bruno
authors.initials: B
authors.lastname: Annibale
authors.forename: Soraia
authors.initials: S
authors.lastname: Melo
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Francesca
authors.initials: F
authors.lastname: De Lorenzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferrara
authors.forename: Riccardo
authors.initials: R
authors.lastname: Piagnerelli
authors.forename: Franco
authors.initials: F
authors.lastname: Roviello
authors.forename: Viviana
authors.initials: V
authors.lastname: Galimberti
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015820:Cadherins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D015316:Genetic Therapy; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D015820:Cadherins