Cagri DOGAN, Cengiz AKOSMAN, Muge SONMEZ
The Atlantic Journal of Medical Science and Research - 2026;6(1):93-99
Aim: This study aimed to determine the spectrum BRCA1/2 variants in patients with suspected hereditary breast cancer from Ordu Province. Materials and Methods: The medical records of patients evaluated at Ordu University between January 1, 2023, and September 1, 2025, were retrospectively reviewed. A total of 357 patients who underwent BRCA1/2 gene sequencing and MLPA analyses were included. All variants were classified according to ACMG guidelines. Findings were summarized descriptively. Results: Of the 357 individuals, 41 patients (11.5%) carried at least one BRCA1/2 variant classified as pathogenic (P), likely pathogenic (LP), or variant of uncertain significance (VUS). A total of 28 BRCA1 and 15 BRCA2 variants were identified. In BRCA1, pathogenic variants predominated (n=19), whereas BRCA2 showed a higher proportion of VUS (n=11). The most frequent alteration was the BRCA1 exon 18-19 deletion, detected in eight patients. Recurrent sequence-level variants included BRCA1:c.788dup (n=4), BRCA2:c.5975C>T (n=3), BRCA1:c.1504_1508del (n=2), BRCA1:c.135-8A>G (n=2), BRCA2:c.5120del (n=2), and BRCA2:c.7481G>A (n=2). Variation-type analysis revealed that missense variants (n=18) were the most common, followed by frameshift variants (n=10) and large genomic deletions (n=9). Five patients (1.4%) harbored more than one variant simultaneously. Conclusion: This study represents the first comprehensive analysis of BRCA1/2 variant distribution in the Central Black Sea region of Türkiye and highlights a distinct mutational spectrum compared with previously published national data. The high frequency of the BRCA1 exon 18-19 deletion and the detection of region-specific recurrent variants emphasize the importance of incorporating MLPA and broad NGS panels into routine genetic evaluation. Given the dominance of VUS findings in BRCA2 and the presence of multiple variants in individual patients, regular reclassification and family-based cascade screening are essential. These results underscore the need for region-specific genomic databases to improve risk assessment, early diagnosis, and precision-guided management in hereditary breast cancer.
