MOLECULAR GENETIC DIAGNOSIS OF HEREDITARY BREAST AND OVARIAN CANCER: THE ROLE OF BRCA1/2 VARIANTS, PCR, AND TARGETED NEXT-GENERATION SEQUENCING (A LITERATURE REVIEW)

Abstract

Relevance: Hereditary breast and ovarian cancer represents a significant cause of cancer morbidity and mortality among women. Pathogenic variants in the BRCA1 and BRCA2 genes play a central role in its development, as their products help maintain genome stability and repair DNA double-strand breaks through homologous recombination.The study aimed to summarize current data on the biological functions of BRCA1/2 and the mech-anisms of carcinogenesis, as well as compare the diagnostic capabilities of molecular genetic meth-ods for detecting hereditary predisposition to breast and ovarian cancer.Materials and Methods: The study was conducted as a structured narrative review which included original studies, systematic and thematic reviews, international clinical guidelines, professional or-ganization documents, and official statistical data on cancer morbidity in Kazakhstan. The search used terms related to BRCA1/2, hereditary breast and ovarian cancer, homologous recombination deficiency, polymerase chain reaction, Sanger sequencing, next-generation sequencing, variant in-terpretation, and genetic counseling. Publications from the past ten years were prioritized.Results: We analyzed scientific publications, international guidelines, and official statistical data. The advantages and limitations of polymerase chain reaction, Sanger sequencing, and targeted next-generation sequencing were considered. Particular attention was paid to the classification of genetic variants according to the criteria of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, interpretation of variants of uncertain significance, genetic counseling, and cascade testing of relatives. Targeted next-generation sequencing with exon copy-number analysis was identified as the primary method for comprehensive assessment of hereditary predisposition.Conclusion: Pathogenic germline variants in BRCA1 and BRCA2 are a key factor in hereditary predisposition. Polymerase chain reaction and Sanger sequencing are important for known variants and confirmation of results, whereas targeted next-generation sequencing provides the most compre-hensive diagnostic coverage. Identified variants should be interpreted according to established crite-ria; a variant of uncertain significance is not a basis for irreversible preventive or therapeutic deci-sions.