title: Germline mutation of the E-cadherin gene in three sibling cases with advanced gastric cancer: clinical consequences for the other family members.
abstract: OBJECTIVE
  Germline mutations in the E-cadherin (CDH1) gene have been found in families with hereditary diffuse gastric cancer (HDGC). These families are characterized by a highly penetrant susceptibility to diffuse gastric cancer with an autosomal dominant pattern of inheritance. We describe the clinical presentation of three sibling cases with advanced gastric cancer, the way of confirming the suspicion of underlying HDGC and the clinical management of the other healthy family members.
  
  
  METHODS
  Screening for CDH1 germline mutation was carried out by denaturing high-performance liquid chromatography and automated DNA sequencing. The clinical suspicion of HDGC has been confirmed by identifying a frameshift mutation in exon 9 (1302_1303insA, 1306_1307delTT) of the E-cadherin gene.
  
  
  RESULTS
  Eight of nine tested family members were positive for the CDH1 germline mutation. Prophylactic laparoscopic gastrectomies were performed in five mutation carriers. After pathological examination, we could identify intramucosal malignant signet-ring cell carcinoma in all resected stomachs.
  
  
  CONCLUSIONS
  This report underlines that prophylactic gastrectomy remains the only option to eliminate the high risk for gastric cancer in CDH1 mutation carriers.
authors.affiliation: Fourth Department of Internal Medicine, Klinikum Wels-Grieskirchen, Grieskirchnerstrasse 42, Wels, Austria. beate.mayrbaeurl@kabelkom.at
authors.forename: Beate
authors.initials: B
authors.lastname: Mayrbaeurl
authors.forename: Gisela
authors.initials: G
authors.lastname: Keller
authors.forename: Walter
authors.initials: W
authors.lastname: Schauer
authors.forename: Sonja
authors.initials: S
authors.lastname: Burgstaller
authors.forename: Manfred
authors.initials: M
authors.lastname: Czompo
authors.forename: Walter
authors.initials: W
authors.lastname: Hoebling
authors.forename: Peter
authors.initials: P
authors.lastname: Knoflach
authors.forename: Hans C
authors.initials: HC
authors.lastname: Duba
authors.forename: Heinz
authors.initials: H
authors.lastname: Hoefler
authors.forename: Josef
authors.initials: J
authors.lastname: Thaler
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics*; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D005743:Gastrectomy / Q000379:methods; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D010535:Laparoscopy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010375:Pedigree; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control / Q000601:surgery; D017211:Treatment Failure
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins