Molecular characterization of hereditary breast and ovarian cancer patients from a public precision medicine service in the Southeast Brazilian population.

ABSTRACT: To address the need for specialized care in hereditary cancer, we developed a Hereditary Cancer Predisposition Assessment and Family Monitoring Program in the southeast of Brazil. The program was designed to identify suspected cases and provide molecular diagnostic testing through a structured care flow that included genetic counseling, psychological support, and clinical follow-up. This initiative targeted individuals within the public healthcare system and aimed to implement accessible precision medicine approaches for hereditary cancer syndromes. As part of this initiative, we performed systematic genetic screening using both Sanger sequencing and a next-generation sequencing panel to investigate cancer susceptibility genes in a cohort of 210 patients with suspected Hereditary Breast and Ovarian Cancer Syndrome (HBOC). Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Statistical analyses were conducted to compare clinical characteristics between patients carrying pathogenic or likely pathogenic variants and those with benign findings. Pathogenic or likely pathogenic mutations were identified in 33.3% (70/210) of patients, with 14.3% (30/210) involving non-BRCA genes. BRCA2 was the most frequently mutated gene contrasting with most reports from the country, in which BRCA1 predominates. The most frequent pathogenic mutation was c.4829_4830del in BRCA2, present in 8.57% of positive cases and apparently rare in other Brazilian cohorts. Additionally, 12.8% of the patients with pathogenic or likely pathogenic variants had mutations in genes associated with hereditary cancer syndromes other than HBOC. A total of 35 variants of uncertain significance were identified, most commonly in the ATM gene. By identifying pathogenic mutations in these individuals, precision medicine strategies can be implemented to improve outcomes for patients and their families.

SUBMITTER: Ribeiro AAF 

PROVIDER: S-EPMC12480894 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature