title: CDH1 gene mutations do not contribute in hereditary diffuse gastric cancer in Poland.
abstract: Hereditary diffuse gastric cancer (HDGC) is a cancer susceptibility syndrome characterized by a high risk of diffuse stomach cancer and lobular breast cancer. HDGC is caused by germline mutations in the CDH1 gene encoding the E-cadherin which is a member of the transmembrane glycoprotein family responsible for calcium-dependent, cell-to-cell adhesion and plays a fundamental role in the maintenance of cell differentiation and the normal architecture of epithelial tissues. Mutations in the CDH1 gene are detected in 30-46% of families that fulfil strong clinical criteria for HDGC and in about 11% of families fulfilling the modified criteria. In the present study, we investigated germline mutations in the CDH1 gene in Polish patients with HDGC. The entire coding sequence of CDH1 gene was analyzed by sequencing in 86 Polish cancer patients from families fulfilling the modified criteria of HDGC. We found several silent mutations including one common variant (c.2076T>C) present in 56 patients, and three rare variants (c.2253C>T, c.1896C>T, c.2634C>T) detected in 2 patients. In addition, we found four rare sequence variants of unknown significance localized in introns. We did not detect any deleterious mutations of the CDH1 gene. CDH1 gene mutations are not present in Polish families with HDGC defined by the modified clinical criteria. Further studies of families with HDGC matching the restrictive criteria for HDGC are needed.
authors.affiliation: International Hereditary Cancer Centre, Department of Genetics and Pathology, Pomeranian Medical University, ul Połabska 4, 70-115 Szczecin, Poland. aniaj@sci.pam.szczecin.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Lawniczak
authors.forename: Beata
authors.initials: B
authors.lastname: Wojnarska
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Byrski
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Tołoczko-Grabarek
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jaworska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Durda
authors.forename: Teresa
authors.initials: T
authors.lastname: Starzyńska
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011044:Poland; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D004273:DNA, Neoplasm