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

Authors

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Nikolaos Tsoulos

Genekor, Gerakas, Attica, Greece

Nikolaos Tsoulos , Kevisa Potska , Konstantinos Agiannitopoulos , Georgios Tsaousis , Mustafa Ozdogan , Bulent Karabulut , Adina-Emilia Croitoru , Dimitrios C. Ziogas , Maria Theochari , Christos Christodoulou , Epaminondas Samantas , Dimitrios Janinis , Ilias Athanasiadis , Angelos Koutras , Eirini Papadopoulou , George Nasioulas

Organizations

Genekor, Gerakas, Attica, Greece, GeneKor Medical SA, Gerakas, Greece, Memorial and Medstar, Dokuma, Turkey, Kent Hospital, Izmir, Turkey, Fundeni Clinical Institut, Bucharest, Romania, First Department of Medicine, National and Kapodistrian University of Athens, Athens, Greece, Laiko General Hospital, Athina, Greece, 2nd Oncology Clinic, Metropolitan Hospital, Pireus, Greece, Metropolitan Hospital, Athens, Greece, Athens Medical Center, Athens, Greece, Mitera Hospital-Hygeia, Athina, Greece, University Hospital of Patras, Patras, Greece, Genekor Medical SA, Gerakas, Greece, Genekor, Gerakas, Greece

Research Funding

No funding received
None.

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.

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Publication Only: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Pancreatic Cancer - Advanced/Metastatic Disease

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr e16276)

DOI

10.1200/JCO.2023.41.16_suppl.e16276

Abstract #

e16276

Abstract Disclosures