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BRCA1 and BRCA2 germline variants in breast cancer patients from the Republic of Macedonia

  • Epidemiology
  • Published:
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Abstract

Purpose

We aimed to establish the spectrum of BRCA1/2 mutations among the breast cancer (BC) patients from the Republic of Macedonia.

Methods

We used targeted next-generation sequencing (NGS), Sanger DNA sequencing, and multiplex ligation probe amplification analysis (MLPA) to search for point mutations and deletions/duplications involving BRCA1 and BRCA2-coding regions.

Results

We have analyzed a total of 313 BC patients, enriched for family history of cancer, early age of onset and bilateral and/or triple negative (TN) BC. A total of 26 pathogenic mutations were observed in 49 unrelated BC patients (49/313, 15.7%). BRCA2 mutations (27/49, 55.1%) were more common than BRCA1 mutations (22/49, 44.9%). We identified five novel point mutations, one in BRCA1 (c.4352_4356delA) and four in BRCA2 (c.151G>T, c.4707_4708delCA, c.7811_7814delTGTG, and c.9304_9305delG), as well as two novel deletions involving parts of the BRCA1 gene (c.81−?_593+?del and c.5470−?_5530+?del). The most common mutations were c.181T>G, c.5266dupC, and c.3700_3704del5 in BRCA1 and c.7879A>T, c.8317_8330del14 and c.5722_5723delCT in BRCA2 gene. Thus far, BRCA2 c.7879A>T and c.8317_8330del14 mutations have been described in several isolated cases; however, our study is the first one showing that they have a founder effect among Macedonian population. Nine recurrent mutations account for 65.3% of all of the detected mutations allowing for implementation of a fast first-step BRCA1/2 mutational screening strategy in our country.

Conclusion

This study provides a comprehensive view of known and novel BRCA1/2 mutations in BC patients from the Republic of Macedonia and contributes to the global spectrum of BRCA1/2 mutations in breast cancer.

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Acknowledgements

We cordially thank all patients and clinicians who participated in sampling and documentation.

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Authors and Affiliations

  1. Research Centre for Genetic Engineering and Biotechnology “Georgi D. Efremov”, Macedonian Academy of Sciences and Arts, Krste Misirkov 2, Skopje, Republic of Macedonia

    Milena Jakimovska, Ivana Maleva Kostovska, Katerina Popovska-Jankovic & Dijana Plaseska-Karanfilska

  2. Clinical Hospital Acibadem Sistina, Skopje, Republic of Macedonia

    Katerina Kubelka-Sabit & Mitko Karadjozov

  3. Re-Medika General Hospital, Skopje, Republic of Macedonia

    Liljana Stojanovska & Andreja Arsovski

  4. University Clinic of Radiotherapy and Oncology, Medical Faculty, University “Ss Cyril and Methodius”, Skopje, Republic of Macedonia

    Snezhana Smichkoska & Emilija Lazarova

  5. University Clinic of Radiology, Medical Faculty, University “Ss Cyril and Methodius”, Skopje, Republic of Macedonia

    Maja Jakimovska Dimitrovska

Authors
  1. Milena Jakimovska
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  2. Ivana Maleva Kostovska
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  3. Katerina Popovska-Jankovic
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  4. Katerina Kubelka-Sabit
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  5. Mitko Karadjozov
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  6. Liljana Stojanovska
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  7. Andreja Arsovski
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  8. Snezhana Smichkoska
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  9. Emilija Lazarova
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  10. Maja Jakimovska Dimitrovska
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  11. Dijana Plaseska-Karanfilska
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Corresponding author

Correspondence to Dijana Plaseska-Karanfilska.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committees and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Jakimovska, M., Maleva Kostovska, I., Popovska-Jankovic, K. et al. BRCA1 and BRCA2 germline variants in breast cancer patients from the Republic of Macedonia. Breast Cancer Res Treat 168, 745–753 (2018). https://doi.org/10.1007/s10549-017-4642-5

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