BRCA1/2 Pathogenic Variants in a Turkish Cohort: Clinical Spectrum, Novel Truncating Variants, and Non-Canonical Cancers in the Aegean Region

Le résumé fourni par la source

Objective: To investigate the clinical and molecular spectrum of pathogenic and likely pathogenic BRCA1/2 variants in a regional cohort from the Aegean region of Türkiye, with particular emphasis on novel truncating variants and non-canonical cancer presentations.Methods: We retrospectively analysed clinical and genetic data from 1,171 individuals who underwent multigene hereditary cancer panel testing at a tertiary care centre. Germline BRCA1/2 variants were identified using next-generation sequencing, and variant classification was performed according to American College of Medical Genetics and Genomics guidelines. Only unrelated individuals carrying pathogenic or likely pathogenic variants were included in the final analysis.Results: Seventy unrelated individuals (6.0%) carried pathogenic or likely pathogenic BRCA1/2 variants. BRCA1 variants were more frequent, whereas BRCA2 variants showed greater heterogeneity. A total of 47 distinct variants were identified, including five novel truncating variants absent from public databases. While breast and ovarian cancers predominated, four individuals (5.7%) presented with non-canonical malignancies, including endometrial, gastric, lymphoid, and multiple primary cancers.Conclusion: Our findings expand the phenotypic and molecular spectrum of BRCA1/2-associated cancers in an underrepresented population. The identification of novel truncating variants and non-canonical cancer presentations highlights the importance of region-specific genomic data and supports broader clinical consideration of BRCA testing beyond classical HBOC phenotypes.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.