Strong founder effect for BRCA1 c.3629_3630delAG pathogenic variant in Chechen patients with breast or ovarian cancer

• Published in: Cancer medicine (Malden, MA) Vol. 12; no. 3; pp. 3167 - 3171
• Main Authors: Sokolenko, Anna P., Sultanova, Luisa V., Stepanov, Ilya A., Romanko, Alexandr A., Venina, Aigul R., Sokolova, Tatiana N., Musayeva, Hedi S., Tovgereeva, Marina Ya, Magomedova, Mareta Kh, Akhmatkhanov, Khusein U., Vagapova, Elisa I., Suleymanov, Elkhan A., Vasilyeva, Elena V., Bakaeva, Elvina Kh, Bizin, Ilya V., Aleksakhina, Svetlana N., Imyanitov, Evgeny N.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.02.2023; John Wiley and Sons Inc; Wiley
• Subjects: Alleles; BRCA1 and BRCA2 testing; BRCA1 protein; BRCA1 Protein - genetics; BRCA2 protein; Breast cancer; Breast Neoplasms - genetics; Brief Communication; Chechens; Disease; Ethnicity; Family medical history; Female; Founder Effect; founder mutation; Genes, BRCA2; Genetic analysis; Genetic Predisposition to Disease; Genetic testing; Germ-Line Mutation; Heterozygotes; Humans; Minority & ethnic groups; Mutation; next‐generation sequencing; Ovarian cancer; Ovarian Neoplasms - genetics; p53 Protein; Patients; Single-nucleotide polymorphism; Student's t-test; Womens health; France; Russia; Chechens; breast cancer; BRCA1 and BRCA2 testing; next-generation sequencing; ovarian cancer; founder mutation
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.5159

Coding sequences of BRCA1, BRCA2, ATM, TP53, and PALB2 genes were analyzed in 68 consecutive Chechen patients with high‐grade serous ovarian cancer (HGSOC). Pathogenic BRCA1/2 variants were identified in 15 (22%) out of 68 HGSOC cases. Nine out of ten patients with BRCA1 pathogenic alleles carried the same deletion (c.3629_3630delAG), and three out of five BRCA2 heterozygotes had Q3299X allele. The analysis of 49 consecutive patients with triple‐negative breast cancer (TNBC) revealed 3 (6%) additional BRCA1 heterozygotes. All women with BRCA1 c.3629_3630delAG allele also carried linked c.1067G>A (Q356R) single nucleotide polymorphism, indicating that this is a genuine founder variant but not a mutational hotspot. An ATM truncating allele was detected in one HGSOC patient. There were no women with TP53 or PALB2 germline alterations. Genetic analysis of non‐selected HGSOC patients is an efficient tool for the identification of ethnicity‐specific BRCA1/2 pathogenic variants. Coding sequences of BRCA1, BRCA2, ATM, TP53, and PALB2 were analyzed in 68 consequtive Chechen patients with high‐grade serous ovarian cancer and 79 patients with breast cancer. The recurrent BRCA1 pathogenic variant was identified.