Ilario Giovanni Rapposelli1, Valentina Zampiga2, Ilaria Cangini3, Valentina Arcangeli4, Mila Ravegnani5, Martina Valgiusti1, Sara Pini6, Stefano Tamberi7, Giulia Bartolini1, Alessandro Passardi1, Giovanni Martinelli8, Daniele Calistri3, Giovanni Luca Frassineti1, Fabio Falcini5, Rita Danesi5. 1. Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST, 47014, Meldola, Italy. 2. Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST, 47014, Meldola, Italy. valentina.zampiga@irst.emr.it. 3. Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST, 47014, Meldola, Italy. 4. Department of Medical Oncology, Degli Infermi Hospital, 47923, Rimini, Italy. 5. Romagna Cancer Registry, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST, 47014, Meldola, Italy. 6. Medical Oncology Unit, Department of Oncology AUSL Romagna, Degli Infermi Hospital, Rimini, Italy. 7. Oncology Unit, Ravenna Hospital, AUSL Romagna, Ravenna, Italy. 8. Scientific Directorate, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST, 47014, Meldola, Italy.
Abstract
BACKGROUND: Pancreatic cancer (PC) is a major cause of cancer death. In an effort to improve treatment strategies and outcomes, DNA damage repair (DDR) pathways have been introduced as a new target in PC and in other cancers, through the exploitation of synthetic lethality. Furthermore, genes involved in DDR are among the major determinants of cancer susceptibility. In addition to the well-known BRCA1 and BRCA2 genes, a plethora of other targets in the same pathways are now emerging. METHODS: We analyzed samples from 60 patients, affected by PC and already tested for BRCA, using a panel with 24 other cancer susceptibility genes. RESULTS: We detected 8 pathogenic or likely pathogenic mutations (13.3% of samples analyzed), 4 of which were found in non-BRCA genes (2 in ATM, 1 each in PALB2 and RAD50). Furthermore, 4 pathogenic or likely pathogenic mutations were found in patients without a personal or familial history of cancer. CONCLUSIONS: Our results suggest that genetic testing with a comprehensive gene panel should be perfomed in all patients with PC, in order to allow screening for PC and other gene-related cancers in all at risk family members and to assess patients' eligibility for emerging therapeutic options.
BACKGROUND:Pancreatic cancer (PC) is a major cause of cancer death. In an effort to improve treatment strategies and outcomes, DNA damage repair (DDR) pathways have been introduced as a new target in PC and in other cancers, through the exploitation of synthetic lethality. Furthermore, genes involved in DDR are among the major determinants of cancer susceptibility. In addition to the well-known BRCA1 and BRCA2 genes, a plethora of other targets in the same pathways are now emerging. METHODS: We analyzed samples from 60 patients, affected by PC and already tested for BRCA, using a panel with 24 other cancer susceptibility genes. RESULTS: We detected 8 pathogenic or likely pathogenic mutations (13.3% of samples analyzed), 4 of which were found in non-BRCA genes (2 in ATM, 1 each in PALB2 and RAD50). Furthermore, 4 pathogenic or likely pathogenic mutations were found in patients without a personal or familial history of cancer. CONCLUSIONS: Our results suggest that genetic testing with a comprehensive gene panel should be perfomed in all patients with PC, in order to allow screening for PC and other gene-related cancers in all at risk family members and to assess patients' eligibility for emerging therapeutic options.
Entities:
Keywords:
Cancer susceptibility; DNA damage repair; Gene panel; Pancreatic cancer; Targeted therapy
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