title: Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer.
abstract: We have undertaken a hospital-based study, to identify possible BRCA1 and BRCA2 founder mutations in the Polish population. The study group consisted of 66 Polish families with cancer who have at least three related females affected with breast or ovarian cancer and who had cancer diagnosed, in at least one of the three affected females, at age <50 years. A total of 26 families had both breast and ovarian cancers, 4 families had ovarian cancers only, and 36 families had breast cancers only. Genomic DNA was prepared from the peripheral blood leukocytes of at least one affected woman from each family. The entire coding region of BRCA1 and BRCA2 was screened for the presence of germline mutations, by use of SSCP followed by direct sequencing of observed variants. Mutations were found in 35 (53%) of the 66 families studied. All but one of the mutations were detected within the BRCA1 gene. BRCA1 abnormalities were identified in all four families with ovarian cancer only, in 67% of 27 families with both breast and ovarian cancer, and in 34% of 35 families with breast cancer only. The single family with a BRCA2 mutation had the breast-ovarian cancer syndrome. Seven distinct mutations were identified; five of these occurred in two or more families. In total, recurrent mutations were found in 33 (94%) of the 35 families with detected mutations. Three BRCA1 abnormalities-5382insC, C61G, and 4153delA-accounted for 51%, 20%, and 11% of the identified mutations, respectively.
authors.affiliation: Department of Genetics and Pathology, Hereditary Cancer Center, 70-115 Szczecin, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Górski
authors.forename: T
authors.initials: T
authors.lastname: Byrski
authors.forename: T
authors.initials: T
authors.lastname: Huzarski
authors.forename: A
authors.initials: A
authors.lastname: Jakubowska
authors.forename: J
authors.initials: J
authors.lastname: Menkiszak
authors.forename: J
authors.initials: J
authors.lastname: Gronwald
authors.forename: A
authors.initials: A
authors.lastname: Pluzańska
authors.forename: M
authors.initials: M
authors.lastname: Bebenek
authors.forename: L
authors.initials: L
authors.lastname: Fischer-Maliszewska
authors.forename: E
authors.initials: E
authors.lastname: Grzybowska
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
authors.forename: J
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D000328:Adult; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency / Q000235:genetics; D019398:Genes, BRCA1 / Q000235:genetics*; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics*; D011044:Poland; D018807:Polymorphism, Single-Stranded Conformational; D014157:Transcription Factors / Q000235:genetics
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors