Csonka Katalin, Baghy Kornélia
Semmelweis Egyetem, Patológiai és Kísérleti Rákkutató Intézet, Molekuláris Diagnosztika Részleg, Budapest
Mutations in BRCA1 and BRCA2 genes play a crucial role in the development of solid tumors, especially breast and ovarian cancer. These genes are essential for repairing DNA double-strand breaks, and their absence or damage prevents cells from repairing these lesions. BRCA1/2 mutant tumor cells are particularly sensitive to PARP inhibitors, which cause additional DNA damage and cell death by accelerating apoptosis. As the lifetime risk of developing tumors is substantially increased in individuals who inherit mutations in these genes, the analysis of BRCA1/2 mutations is crucial for cancer prevention and early detection. In addition, the identification of both somatic and germline pathogenic variants is an essential element in selecting appropriate therapeutic interventions and patient management. The advent of next-generation sequencing has enabled the comprehensive coverage of these two large genes, as well as the simultaneous analysis of other genes linked to hereditary cancer syndromes. The future is likely to include the analysis of larger gene panels associated with specific diseases. Nonetheless, it should be kept in mind that technology is generally always ahead of legal and ethical regulations, so interpretation of germline variants should always be performed within the context of clinical genetic counselling.