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Cancer predisposing BARD1 mutations in breast–ovarian cancer families

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Abstract

The breast cancer susceptibility gene BARD1 (BRCA1-associated RING domain protein, MIM# 601593) acts with BRCA1 in DNA double-strand break (DSB) repair and also in apoptosis initiation. We screened 109 BRCA1/2 negative high-risk breast and/or ovarian cancer patients from North-Eastern Poland for BARD1 germline mutations using a combination of denaturing high-performance liquid chromatography and direct sequencing. We identified 16 different BARD1 sequence variants, five of which are novel. Three of them were suspected to be pathogenic, including a protein truncating nonsense mutation (c.1690C>T, p.Gln564X), a splice mutation (c.1315-2A>G) resulting in exon 5 skipping, and a silent change (c.1977A>G) which alters several exonic splicing enhancer motifs in exon 10 and results in a transcript lacking exons 2–9. Our findings suggest that BARD1 mutations may be regarded as cancer risk alleles and warrant further investigation to determine their actual contribution to non-BRCA1/2 breast and ovarian cancer families.

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Acknowledgments

The cooperation of all the patients and their families who participated in this study was invaluable. We thank to Rafal Dziadziuszko for help with editing the manuscript, Anna Stanislawska-Sachadyn and Bartosz Wasag for laboratory assistance. This study was supported by a grant from MNiSW: N401 164 31/3656 and N407 627740.

Conflicts of interest

None of the authors have any conflicts of interest to declare. Authors also do not have a financial relationship with any of the organizations that sponsored the research. Authors have full control of all primary data and agree to allow the journal to review the data if requested.

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Authors and Affiliations

  1. Department of Biology and Genetics, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, Poland

    Magdalena Ratajska, Ewelina Antoszewska, Anna Piskorz, Izabela Brozek & Janusz Limon

  2. Regional Oncological Outpatient Clinic, Sklodowskiej-Curie 2, 80-211, Gdansk, Poland

    Izabela Brozek & Janusz Limon

  3. Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden

    Åke Borg

  4. Intercollegiate Faculty of Biotechnology UG-MUG, Kladki 24, 80-822, Gdansk, Poland

    Hanna Kusmierek

  5. Department of Pathology, Medical University of Gdansk, Debinki 7, 80-211, Gdansk, Poland

    Wojciech Biernat

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  1. Magdalena Ratajska
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Correspondence to Magdalena Ratajska.

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Ratajska, M., Antoszewska, E., Piskorz, A. et al. Cancer predisposing BARD1 mutations in breast–ovarian cancer families. Breast Cancer Res Treat 131, 89–97 (2012). https://doi.org/10.1007/s10549-011-1403-8

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