Spectrum of High-Risk Mutations among Breast Cancer Patients Referred for Multigene Panel Testing in a Romanian Population

SIMPLE SUMMARY: Multigene panel testing for Hereditary Breast and Ovarian Cancer using next generation sequencing is the new standard for the identification of individuals with cancer predisposing gene variants. The purpose of our research was to investigate the genetic variants implicated in hereditary breast cancer predisposition in 255 Romanian individuals referred for management. In our cohort, gene analysis found most oncogenic mutations in BRCA 1/2 genes, followed by the high penetrance PALB2 and TP53 genes, while in the CDH1 and STK11 genes only VUS mutations were identified. Multigene testing of populations of different geographical and ethnical backgrounds, followed by data merging, will enable us to map the clinical significance of genetic variants and tailor management decisions for Hereditary Breast and Ovarian Cancer patients. ABSTRACT: (1) Background: Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing (NGS) is becoming a standard in medical care. There are insufficient genetic studies reported on breast cancer (BC) patients from Romania and most of them are focused only on BRCA 1/2 genes (Breast cancer 1/2). (2) Methods: NGS was performed in 255 consecutive cases of BC referred for management in our clinic between 2015–2019. (3) Results: From the 171 mutations identified, 85 were in the high-penetrance BC susceptibility genes category, 72 were pathogenic genes, and 13 genes were in the (variants of uncertain significance) VUS genes category. Almost half of the mutations were in the BRCA 1 gene. The most frequent BRCA1 variant was c.3607C>T (14 cases), followed by c.5266dupC (11 cases). Regarding BRCA-2 mutations we identified c.9371A>T (nine cases), followed by c.8755-1G>A in three cases, and we diagnosed VUS mutations in three cases. We also identified six pathogenic variants in the PALB2 gene and two pathogenic variants in (tumor protein P 53) TP53. (4) Conclusions: The majority of pathogenic mutations in the Romanian population with BC were in the BRCA 1/ 2 genes, followed by PALB2 (partner and localizer of BRCA2) and TP53, while in the CDH1 (cadherin 1) and STK11 (Serine/Threonine-Protein Kinase) genes we only identified VUS mutations.