title: A germline E-cadherin mutation in a family with gastric and colon cancer.
abstract: Inactivating mutations have been found in the cell-cell adhesion molecule E-cadherin (CDH1), which acts as a tumor suppressor gene in different kinds of cancers, e.g. primarily diffuse gastric cancer and lobular breast cancer. In this study, we screened for germline alterations in familial gastric and colon cancer cases. In total, 20 gastric and 18 colon cancer patients with both familial gastric and colon cancer were tested for germline E-cadherin alterations by using PCR/SSCP, specific restriction digestion test and sequencing. No pathogenic mutations were identified in the gastric cancer patients. In two colon cancer patients, a missense mutation in exon 12, codon 592 (Ala592Thr) was found. This alteration segregated with diffuse gastric cancer and colon cancer in one of the families. The prevalence of this alteration in the general population and colon cancer cases was almost the same. However, the fact that this alteration (Ala592Thr) segregated with colon cancer and diffuse gastric cancer in one big family, suggests that this E-cadherin missense alteration, beside predisposing to diffuse gastric cancer, also may play a role in colorectal carcinogenesis.
authors.affiliation: Department of Molecular Medicine, Karolinska Institute, S-171 76 Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Salahshor
authors.forename: H
authors.initials: H
authors.lastname: Hou
authors.forename: C B
authors.initials: CB
authors.lastname: Diep
authors.forename: A
authors.initials: A
authors.lastname: Loukola
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Iselius
authors.forename: C
authors.initials: C
authors.lastname: Rubio
authors.forename: R A
authors.initials: RA
authors.lastname: Lothe
authors.forename: L
authors.initials: L
authors.lastname: Aaltonen
authors.forename: X F
authors.initials: XF
authors.lastname: Sun
authors.forename: G
authors.initials: G
authors.lastname: Lindmark
authors.forename: A
authors.initials: A
authors.lastname: Lindblom
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D015820:Cadherins / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D015820:Cadherins; D004273:DNA, Neoplasm