TY - JOUR

T1 - A spectrum of BRCA1 and BRCA2 germline deleterious variants in ovarian cancer in Russia

AU - Kechin, Andrey

AU - Boyarskikh, Ulyana

AU - Barinov, Alexey

AU - Tanas, Alexander

AU - Kazakova, Svetlana

AU - Zhevlova, Anastasia

AU - Khrapov, Evgeniy

AU - Subbotin, Sergey

AU - Mishukova, Olga

AU - Kekeeva, Tatiana

AU - Demidova, Irina

AU - Filipenko, Maxim

N1 - Funding Information: 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. Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

PY - 2023/1

Y1 - 2023/1

N2 - 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.

AB - 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.

KW - BRCA1/2

KW - Germline mutations

KW - Hotspot

KW - NGS

KW - Ovarian cancer

UR - http://www.scopus.com/inward/record.url?scp=85141697883&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/805f6f38-8777-3875-9447-6d801ac26a2e/

U2 - 10.1007/s10549-022-06782-2

DO - 10.1007/s10549-022-06782-2

M3 - Article

C2 - 36367610

AN - SCOPUS:85141697883

VL - 197

SP - 387

EP - 395

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 2

ER -