Germline BRCA1/2 Variants in Polish Patients with Family History of Breast and Ovarian Cancer: Prevalence, CNV Detection, and Identification of a Novel Loss-of-Function Mutation.

BACKGROUND/

OBJECTIVES

Pathogenic and likely pathogenic variants in the BRCA1 and BRCA2 genes are associated with a significantly increased risk of breast and/or ovarian cancer. We investigated genetic variants in a cohort of 450 unaffected individuals with a family history of breast and/or ovarian cancer, involving at least one first-degree relative.

METHODS

Next-generation sequencing (NGS) was used to analyze the coding regions of these two genes, with copy number variation (CNV) analysis.

RESULTS

A total of 16 unique to our cohort variants classified as pathogenic or likely pathogenic were identified in 22 patients, including one novel loss-of-function variant in BRCA1 gene. Furthermore, we identified a deletion of exon 21 in the BRCA1 gene in two patients.

CONCLUSIONS

These results emphasize the difficulties involved in molecular diagnostics and indicate the need for further research into new predictive models for patients with hereditary breast and ovarian cancer.