Phát hiện các đột biến gây bệnh trên gen BRCA1/2 ở bệnh nhân ung thư vú Việt Nam bằng giải trình tự thế hệ mới (NGS): Báo cáo ca lâm sàng

Breast cancer is a prevalent global health issue, with genetic predisposition, particularly through BRCA1/2 gene mutations, playing a significant role in its development and prognosis. Accurate identification of these pathogenic variants is crucial for early detection, comprehensive risk assessment, and guiding therapeutic decisions. Next-Generation Sequencing (NGS) has emerged as a powerful and indispensable tool in this domain, offering comprehensive and precise mutation detection capabilities. This study highlights the utility of NGS by identifying clinically significant BRCA1/2 variants in Vietnamese breast cancer patients. It serves as a clinical case report to demonstrate the application of this advanced technology in a local context, emphasizing its pivotal role in improving patient management and informing genetic counseling strategies.

Medical professionals specializing in oncology, genetics, and molecular pathology; genetic counselors; and researchers interested in hereditary breast cancer and advanced genomic sequencing technologies.

This clinical case report details the identification of three pathogenic BRCA1/2 mutations in four Vietnamese breast cancer patients, leveraging the capabilities of Next-Generation Sequencing (NGS). The identified variants included one nonsense mutation (p.Arg1751Ter) and two frameshift mutations (p.Glu23ArgfsTer18, p.Glu1493ValfsTer10). A significant finding was the detection of the p.Glu1493ValfsTer10 variant, a highly clinically relevant pathogenic germline mutation, in a mother-child pair, unequivocally demonstrating its hereditary pattern. All identified mutations were rigorously classified as pathogenic following the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) 2015 guidelines, corroborated by reputable databases such as ClinVar and BIC. The methodology involved extracting total DNA from peripheral blood, preparing DNA libraries using the BRCAaccuTest™ PLUS kit, performing sequencing on a MiSeqDx system, and analyzing data with NgeneAnalysis and IGV software. These findings underscore the profound utility of NGS in detecting hereditary mutations, which is paramount for accurate genetic counseling, comprehensive risk assessment, and implementing personalized treatment strategies for individuals with breast cancer. The study contributes valuable local data, reinforcing the global understanding of BRCA1/2-related breast cancer and advocating for the broader integration of NGS into clinical practice.