Background: Mutations of the BRCA1/2 genes are associated with increased breast and ovarian cancer. The aim of this study was to investigate the founder mutations of the BRCA1 and BRCA2 genes in the Turkish population in the Aegean region as well as their genotype-phenotype correlations.
Methods: All the patients were provided with BRCA1/2 testing criteria according to the National Comprehensive Cancer Network. QIAseq Targeted DNA Panels were used for the BRCA1/2 coding regions.
Results: Of the 181 studied patients, 38 (21%) were found to carry pathogenic or likely pathogenic mutations, while 20 (11%) patients were found to carry variants of unknown significance. The most common pathogenic mutations were NM_000059.4:c.2765dup in the BRCA2 gene and NM_007300.4:c.981_982del and NM_007294.3:c. 5266dup in the BRCA1 gene. p.Lys3326* was the most frequently detected variant of unknown significance (6/ 181). Regarding genotype-phenotype correlations, the NM_007300.4:c.981_982del mutation in BRCA1 gene was found to be milder in terms of breast cancer. The most frequent cancers other than those related to BRCA genes, observed in the relatives of the patients who had pathogenic variants and variants of unknown significance, were endometrium cancer and leukemia, respectively.
Conclusions: NM_007294.3:c.5266dup was found to be a candidate founder mutation in the Turkish population. NM_007300.4:c.981_982del mutation seems to have a milder course in terms of breast cancer. A significantly increased frequency of p.Lys3326* variant in breast cancer and ovarian cancer patients compared with that in the 1,000 Genomes Project suggesting that this variant has a slight effect on BRCA2 function.