558 Non-BRCA1/2 pathogenic/likely pathogenic variants detected in 2.6% of patients with ovarian, fallopian tube or primary peritoneal cancer

Abstract

<h3>Introduction/Background*</h3> In Slovenia, ovarian cancer is diagnosed in approximately 160 women per year. The majority of patients are diagnosed with advanced disease and the survival rate is poor. 20 – 30% of cases can be attributed to germline pathogenic/likely pathogenic variants (P/LPV) in genes, associated with hereditary breast and ovarian cancer syndrome (HBOC). P/LPV in <i>BRCA1/2</i> genes are the most prevalent. With the development of new methods for genetic testing, such as next generation sequencing (NGS), associations between non-<i>BRCA</i> genes and HBOCare being discovered. <h3>Methodology</h3> We analyzed genetic results of patients with the diagnosis of ovarian, fallopian tube or primary peritoneal cancer, who were concecutively referred for genetic assessment at our institution in the period between September 2014 and April 2021. Since September 2014 all such patients are routinely tested with NGS with a panel (TruSight Cancer panel or TruSight Hereditary Cancer panel) of 19 HBOC genes. In some cases, an analysis of tumor tissue was also performed. <h3>Result(s)*</h3> During the observation period, 744 patients were tested for germline P/LPV in HBOC gene panel. P/LPV was found in 226/744 (30.4%) of tested patients. 207/744 (27.8%) of patients had P/LPV in <i>BRCA1/2</i>. Non-<i>BRCA</i> P/LPVs were found in 19 patients (2.6%), one patient had a P/LPV in both <i>ATM</i> and <i>RAD51C</i> genes (figure 1). The most common P/LPVs in non-<i>BRCA</i> genes were detected in <i>ATM</i> gene, and were diagnosed in 6 patients (figure 2). The results of tumor tissue testing were available for 7/19 non<i>BRCA</i>-positive patients and in 1 biallelic <i>PALB2</i> inactivation was found. <h3>Conclusion*</h3> Among 744 consecutively tested patients with ovarian, fallopian tube or primary peritoneal cancer, we detected a high P/LPV rate (30.4%). 27.8% of all tested patients were diagnosed with <i>BRCA1/2</i> P/LPVs. P/LPVs in other than <i>BRCA1/2</i> genes were detected less frequently (2.6%). It is, however, important to be aware that P/LPVs in genes other than<i> BRCA1/2</i>can be detected in patients with ovarian cancer and that these women may also benefit from targeted treatment, preventive measures and further cascade testing in the family. Tumor testing may also reveal new treatment targets and help explain carcinogenesis in these patients.