title: BRCA1 and BRCA2 mutation analysis in breast-ovarian cancer families from northeastern Poland.
abstract: Sixty high-risk breast and/or ovarian cancer families from North-Eastern Poland were screened for germline mutations in BRCA1 (MIM# 113705) and BRCA2 (MIM# 600185), using a combination of protein truncation test, denaturing high-performance liquid chromatography and direct sequencing. Sixteen (27%) of the families were found to carry nine different BRCA mutations, including 14 families with BRCA1 mutation and two families with BRCA2 mutation. The results suggest the presence of two strong BRCA1 founder mutations in the Polish population - 5382insC (6 families) and 300T>G (Cys61Gly; 3 families). The remaining seven mutations were found in single families and included three previously reported BRCA1 mutations (185delAG, 2682C>T [Gln855Ter] and 3819del5), a novel BRCA1 mutation (IVS14+1G>A), as well as two BRCA2 mutations (4088delA and 7985G>A [Trp2586Ter]) not previously observed in Polish families. We confirm the strong influence of two Central-Eastern European BRCA1 founder mutations in familial breast and/or ovarian cancer in Poland. We also conclude that the Polish population has a more dispersed BRCA mutation spectrum than had been earlier thought. This warrants further careful BRCA mutation screening in order to optimise genetic counselling and disease prevention in affected families.
authors.affiliation: Department of Biology and Genetics, Medical University of Gdańsk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Perkowska
authors.forename: Izabela
authors.initials: I
authors.lastname: BroZek
authors.forename: Barbara
authors.initials: B
authors.lastname: Wysocka
authors.forename: Karin
authors.initials: K
authors.lastname: Haraldsson
authors.forename: Therese
authors.initials: T
authors.lastname: Sandberg
authors.forename: Ulla
authors.initials: U
authors.lastname: Johansson
authors.forename: Gunilla
authors.initials: G
authors.lastname: Sellberg
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Janusz
authors.initials: J
authors.lastname: Limon
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D011044:Poland; D017384:Sequence Deletion
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004273:DNA, Neoplasm