Comprehensive analysis of DNA damage repair genes reveals pathogenic variants beyond BRCA and suggests the need for extensive genetic testing in pancreatic cancer
Ilario Giovanni Rapposelli,
Valentina Zampiga,
Ilaria Cangini,
Valentina Arcangeli,
Mila Ravegnani,
Martina Valgiusti,
Sara Pini,
Stefano Tamberi,
Giulia Bartolini,
Alessandro Passardi,
Giovanni Martinelli,
Daniele Calistri,
Giovanni Luca Frassineti,
Fabio Falcini,
Rita Danesi
Affiliations
Ilario Giovanni Rapposelli
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” – IRST
Valentina Zampiga
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” – IRST
Ilaria Cangini
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” – IRST
Valentina Arcangeli
Department of Medical Oncology, Degli Infermi Hospital
Mila Ravegnani
Romagna Cancer Registry, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” – IRST
Martina Valgiusti
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” – IRST
Sara Pini
Medical Oncology Unit, Department of Oncology AUSL Romagna, Degli Infermi Hospital
Stefano Tamberi
Oncology Unit, Ravenna Hospital, AUSL Romagna
Giulia Bartolini
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” – IRST
Alessandro Passardi
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” – IRST
Giovanni Martinelli
Scientific Directorate, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” – IRST
Daniele Calistri
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” – IRST
Giovanni Luca Frassineti
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” – IRST
Fabio Falcini
Romagna Cancer Registry, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” – IRST
Rita Danesi
Romagna Cancer Registry, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” – IRST
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.
