Abstract 28P
Background
The spectrum of BRCA1/2 mutations in Slavic countries is characterized by a high prevalence of founder alleles.
Methods
We analyzed a large data set of Russian breast cancer (BC) and ovarian cancer (OC) patients, who were subjected to founder mutation tests or full-length BRCA1/2 analysis.
Results
The most commonly applied test, which included 4 founder mutations (BRCA1: 5382insC, 4153delA, 185delAG; BRCA2: 6174delT), identified BRCA1/2 heterozygosity in 399/8533 (4.7%) consecutive breast cancer (BC) patients, 230/2317 (10%) ovarian cancer (OC) patients and 30/118 (25%) women with a combination of BC and OC. The addition of another four recurrent BRCA1 mutations to the test (BRCA1 C61G, 2080delA, 3819del5, 3875del4) resulted in evident increase in the number of identified mutation carriers (BC: 16/993 (1.6%); OC: 34/1289 (2.6%); BC + OC: 2/39 (5.1%)). Full-length sequencing of the entire BRCA1/2 coding region was applied to 785 women, very most of whom demonstrated clinical signs of BRCA1/2-driven, but turned out negative for all described above founder alleles. This analysis revealed additional BRCA1/2 mutation carriers in 54/282 (19%) BC, 50/472 (10.6%) OC and 13/31 (42%) BC + OC patients. The analysis of frequencies of founder and “rare” BRCA1/2 pathogenic alleles across various clinical subgroups (BC vs. OC vs. BC + OC; family history-positive vs. –negative; young- vs. late-onset; none vs. single vs. multiple clinical indicators of BRCA1/2-associated disease) revealed that comprehensive BRCA1/2 analysis increased more than twice the number of identified mutation carriers in all categories of the examined women.
Conclusions
Full-length BRCA1/2 sequencing is strongly advised to Slavic subjects, who have medical indications for BRCA1/2 testing but are negative for recurrent BRCA1/2 mutations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The study was supported by the Russian Foundation for Basic Research [grant numbers 20-515-00002].
Disclosure
All authors have declared no conflicts of interest.