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A spectrum of BRCA1 and BRCA2 germline deleterious variants in ovarian cancer in Russia

  • Epidemiology
  • Published:
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Abstract

Purpose

Pathogenic variants (PVs) in BRCA1 and BRCA2 genes are essential biomarkers of an increased breast and ovarian cancer risk and tumor sensitivity to poly ADP ribose polymerase inhibitors. In Russia, eight PVs were thought to be the most common, among which BRCA1 c.5266dup is the most frequently identified one.

Methods

We show the distribution of BRCA1/2 PVs identified with quantitative PCR and targeted next-generation sequencing in 1399 ovarian cancer patients recruited into the study from 72 Russian regions in 2015–2021.

Results

The most abundant PVs were c.5266dup (41.0%), c.4035del (7.0%), c.1961del (6.3%), c.181 T > G (5.2%), c.3756_3759del (1.8%), c.3700_3704del (1.5%), and c.68_69del (1.5%), all found in BRCA1 and known to be recurrent in Russia. Several other frequent PVs were identified: c.5152 + 1G > T (1.2%), c.1687C > T (1.0%), c.4689C > G (0.9%), c.1510del (0.6%), c.2285_2286del (0.6%) in the BRCA1 gene; and c.5286 T > G (1.2%), c.2808_2811del (0.8%), c.3847_3848del (0.8%), c.658_659del (0.7%), c.7879A > T (0.6%), in the BRCA2 gene. For the most common PV in the BRCA2 gene c.5286 T > G, we suggested that it arose about 700 years ago and is a new founder mutation.

Conclusion

This study extends our knowledge about the BRCA1 and BRCA2 pathogenic variants variability.

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Data availability

Data supporting the findings of this study are available within the article and its supplementary materials.

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Acknowledgements

The authors greatly appreciate the assistance of the inter-regional non-governmental organization “Society of molecular geneticists in oncology and oncohematology.”

Funding

The study was supported partially under Russian State-funded budget project 0245-2021-0006 “Fundamentals of Health Preservation” and within the state assignment of the Ministry of Science and Higher Education of the Russian Federation for RCMG.

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Contributions

All authors contributed to the study conception and design. AK, UB, AB, AT, SK, AZ, EK, SS, OM: material preparation, data collection, and analysis were performed. The first draft of the manuscript was written by AK, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Andrey Kechin.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The study was approved by the local medical ethics committee of the Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, Ethics approval No 11.

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Informed consent was obtained from all individual participants included in the study.

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Kechin, A., Boyarskikh, U., Barinov, A. et al. A spectrum of BRCA1 and BRCA2 germline deleterious variants in ovarian cancer in Russia. Breast Cancer Res Treat 197, 387–395 (2023). https://doi.org/10.1007/s10549-022-06782-2

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