title: CDH1 germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: a multicentre study.
abstract: BACKGROUND
  CDH1 predisposes primarily to diffuse gastric cancer (DGC). Multiple DGC cases in a family, DGC at a young age in an individual or the combination of DGC andlobular breast cancer (LBC) in an individual or a family define the hereditary DGC syndrome (HDGC), and testing for germline CDH1 mutations is warranted in HDGC.
  
  
  RESULTS
  We report all index cases from Ile-de-France in which a germline CDH1 mutation has been identified. Out of 18 cases, 7 do not fulfil the HDGC-defining criteria. Three of them are women who presented initially with bilateral LBC below age 50, without personal or family history of DGC, and who subsequently developed symptomatic DGC.
  
  
  CONCLUSIONS
  Our series of CDH1 mutation carriers is the largest to date and demonstrates that LBC might be the first manifestation of HDGC. A personal or family history of multiple LBCs at a young age, even without DGC, should prompt CDH1 mutation screening. It is paramount to identify mutation carriers early, so that they can benefit from prophylactic gastrectomy before they develop symptomatic, highly lethal DGC. We recommend a revision of the HDGC-defining criteria and propose for consideration the name 'Hereditary Diffuse Gastric and Lobular Breast Cancer' instead of HDGC.
authors.affiliation: Consultation d'Oncogénétique, Département de Médecine Oncologique, Institut Gustave Roussy, 114 rue Edouard Vaillant, Villejuif 94805, France. pbenusiglio.wk@gmail.com
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Benusiglio
authors.forename: David
authors.initials: D
authors.lastname: Malka
authors.forename: Etienne
authors.initials: E
authors.lastname: Rouleau
authors.forename: Antoine
authors.initials: A
authors.lastname: De Pauw
authors.forename: Bruno
authors.initials: B
authors.lastname: Buecher
authors.forename: Catherine
authors.initials: C
authors.lastname: Noguès
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Fourme
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Colas
authors.forename: Florence
authors.initials: F
authors.lastname: Coulet
authors.forename: Mathilde
authors.initials: M
authors.lastname: Warcoin
authors.forename: Sophie
authors.initials: S
authors.lastname: Grandjouan
authors.forename: Alain
authors.initials: A
authors.lastname: Sezeur
authors.forename: Pierre
authors.initials: P
authors.lastname: Laurent-Puig
authors.forename: Diane
authors.initials: D
authors.lastname: Molière
authors.forename: Camille
authors.initials: C
authors.lastname: Tlemsani
authors.forename: Marina
authors.initials: M
authors.lastname: Di Maria
authors.forename: Veronique
authors.initials: V
authors.lastname: Byrde
authors.forename: Suzette
authors.initials: S
authors.lastname: Delaloge
authors.forename: Martine
authors.initials: M
authors.lastname: Blayau
authors.forename: Olivier
authors.initials: O
authors.lastname: Caron
mesh_terms: D000328:Adult; D015703:Antigens, CD; D001943:Breast Neoplasms / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D013274:Stomach Neoplasms / Q000235:genetics*; D013577:Syndrome
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins
keywords: Cancer: breast; Cancer: gastric; Clinical genetics; Oncology; Prevention