Genetic testing in patients with pancreatic cancer to reveal pathogenic variants in cancer susceptibility genes.

Abstract

e16276 Background: Pancreatic cancer is one of the most fatal malignancies. It accounts for 2% of all cancers and 5% of cancer-related deaths. Hence, it is essential to identify pancreatic cancer at an earlier stage to improve outcomes. A variety of hereditary cancer syndromes have been associated with an increased risk of developing pancreatic cancer, and these individuals may benefit from surveillance plans. PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring germline variant in the Homologous recombination repair (HRR) genes. Our aim was to determine the prevalence of germline pathogenic/likely pathogenic variants in cancer predisposing genes in patients with pancreatic cancer. Methods: In total, 113 patients diagnosed with pancreatic cancer were referred to our laboratory for genetic testing. The analysis of 52 genes involved in hereditary cancer predisposition was performed using a NGS approach. Results: A germline pathogenic/likely pathogenic variant was identified in 20% of patients analyzed. Among individuals with germline pathogenic/likely pathogenic variants, 60% had a positive finding in a pancreatic cancer susceptibility gene; ATM (20%), BRCA1 (20%), BRCA2 (12%), CDKN2A (4%), PALB2 (4%) while 40% carried positive findings in other cancer susceptibility genes. More specifically, in CHEK2 (16%), MRE11 (4%), RAD50 (4%), RAD51C (4%), MUTYH (8%) and NTLH1 (4%). Notably, 84% of pathogenic variants were identified in genes associated with the HRR pathway ( ATM, BRCA1, BRCA2, CHEK2, MRE11, PALB2, RAD50 and RAD51C). Conclusions: Our results indicate that multigene genetic testing is meaningful for pancreatic cancer patients as in 20% of tested individuals we identified findings associated with pancreatic or other cancer predisposition. Moreover, pathogenic/likely pathogenic variants in HRR genes, were identified in 16.6% patients and these patients might benefit from targeted treatments, such as PARP inhibitors or platinum-based treatment.