title: Analysis of large mutations in BARD1 in patients with breast and/or ovarian cancer: the Polish population as an example.
abstract: Only approximately 50% of all familial breast cancers can be explained by known genetic factors, including mutations in BRCA1 and BRCA2. One of the most extensively studied candidates for breast and/or ovarian cancer susceptibility is BARD1. Although it was suggested that large mutations may contribute substantially to the deleterious variants of BARD1, no systematic study of the large mutations in BARD1 has been performed. To further elucidate the role of large mutations in BARD1, we designed a multiplex ligation-dependent probe amplification (MLPA) assay and performed an analysis of 504 women with a familial breast and/or ovarian cancer and 313 patients with ovarian cancer. The investigation did not reveal any large mutations in the BARD1 gene. Although the analysis was not focused on identification of small mutations, we detected seven deleterious or potentially deleterious point mutations, which contribute substantially to the total number of BARD1 mutations detected so far. In conclusion, although we cannot exclude the presence of large mutations in BARD1, our study indicates that such mutations do not contribute substantially to the risk of breast and/or ovarian cancer. However, it has to be noted that our results may be specific to the Polish population.
authors.affiliation: European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Klonowska
authors.affiliation: Medical University of Gdansk, Marii Sklodowskiej-Curie 3a, 80-211 Gdansk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ratajska
authors.affiliation: European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
authors.forename: Karol
authors.initials: K
authors.lastname: Czubak
authors.affiliation: Medical University of Gdansk, Marii Sklodowskiej-Curie 3a, 80-211 Gdansk, Poland.
authors.forename: Alina
authors.initials: A
authors.lastname: Kuzniacka
authors.affiliation: Medical University of Gdansk, Marii Sklodowskiej-Curie 3a, 80-211 Gdansk, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Brozek
authors.affiliation: Medical University of Gdansk, Marii Sklodowskiej-Curie 3a, 80-211 Gdansk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Koczkowska
authors.affiliation: Medical University of Gdansk, Marii Sklodowskiej-Curie 3a, 80-211 Gdansk, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Sniadecki
authors.affiliation: Medical University of Gdansk, Marii Sklodowskiej-Curie 3a, 80-211 Gdansk, Poland.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Debniak
authors.affiliation: Medical University of Gdansk, Marii Sklodowskiej-Curie 3a, 80-211 Gdansk, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Wydra
authors.affiliation: Medical University of Gdansk, Marii Sklodowskiej-Curie 3a, 80-211 Gdansk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Balut
authors.affiliation: Gdynia Oncology Centre, Powstania Styczniowego 1, 81-519 Gdynia, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Stukan
authors.affiliation: 1] European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland [2] Poznan University of Technology, Pl. Marii Sklodowskiej-Curie 5, 60-965 Poznan, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zmienko
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17A, 01-211 Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Nowakowska
authors.affiliation: University Hospitals of Geneva, HUG, Geneva, Switzerland.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Irminger-Finger
authors.affiliation: Medical University of Gdansk, Marii Sklodowskiej-Curie 3a, 80-211 Gdansk, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Limon
authors.affiliation: 1] European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland [2] Poznan University of Technology, Pl. Marii Sklodowskiej-Curie 5, 60-965 Poznan, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kozlowski
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D060885:Multiplex Polymerase Chain Reaction; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases