title: E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.
abstract: To extend earlier observations of germline E-cadherin mutations in kindreds with an inherited susceptibility to diffuse gastric cancer, we searched for germline E-cadherin mutations in five further families affected predominantly by diffuse gastric cancer and one family with a history of diffuse gastric cancer and early-onset breast cancer. Heterozygous inactivating mutations were found in the E-cadherin gene in each of these families. No mutation hotspots were identified. These results demonstrate that germline mutation of the E-cadherin gene is a common cause of hereditary diffuse gastric cancer and suggest a role for these mutations in the incidence of breast cancer.
authors.affiliation: Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, Dunedin, New Zealand. parry.guilford@otago.ac.nz
authors.forename: P J
authors.initials: PJ
authors.lastname: Guilford
authors.forename: J B
authors.initials: JB
authors.lastname: Hopkins
authors.forename: W M
authors.initials: WM
authors.lastname: Grady
authors.forename: S D
authors.initials: SD
authors.lastname: Markowitz
authors.forename: J
authors.initials: J
authors.lastname: Willis
authors.forename: H
authors.initials: H
authors.lastname: Lynch
authors.forename: A
authors.initials: A
authors.lastname: Rajput
authors.forename: G L
authors.initials: GL
authors.lastname: Wiesner
authors.forename: N M
authors.initials: NM
authors.lastname: Lindor
authors.forename: L J
authors.initials: LJ
authors.lastname: Burgart
authors.forename: T T
authors.initials: TT
authors.lastname: Toro
authors.forename: D
authors.initials: D
authors.lastname: Lee
authors.forename: J M
authors.initials: JM
authors.lastname: Limacher
authors.forename: D W
authors.initials: DW
authors.lastname: Shaw
authors.forename: M P
authors.initials: MP
authors.lastname: Findlay
authors.forename: A E
authors.initials: AE
authors.lastname: Reeve
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007962:Leukocytes; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000235:genetics*; D013577:Syndrome
chemical_list: D015820:Cadherins