Clinical Significance of Germline Pathogenic Variants among 51 Cancer Predisposition Genes in an Unselected Cohort of Italian Pancreatic Cancer Patients
Multigene germline panel testing is recommended for Pancreatic Cancer (PC) patients; however, for non-<i>BRCA1/2</i> genes, the clinical utility is unclear. A comprehensive multi-gene assessment in unselected Italian PC patients is missing. We evaluated the prevalence and impact of Patho...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/18/4447 |
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| author | Alberto Puccini Marta Ponzano Bruna Dalmasso Irene Vanni Annalice Gandini Silvia Puglisi Roberto Borea Malvina Cremante William Bruno Virginia Andreotti Eleonora Allavena Valentino Martelli Fabio Catalano Massimiliano Grassi Maria Laura Iaia Chiara Pirrone Alessandro Pastorino Giuseppe Fornarini Stefania Sciallero Paola Ghiorzo Lorenza Pastorino |
| author_facet | Alberto Puccini Marta Ponzano Bruna Dalmasso Irene Vanni Annalice Gandini Silvia Puglisi Roberto Borea Malvina Cremante William Bruno Virginia Andreotti Eleonora Allavena Valentino Martelli Fabio Catalano Massimiliano Grassi Maria Laura Iaia Chiara Pirrone Alessandro Pastorino Giuseppe Fornarini Stefania Sciallero Paola Ghiorzo Lorenza Pastorino |
| author_sort | Alberto Puccini |
| collection | DOAJ |
| description | Multigene germline panel testing is recommended for Pancreatic Cancer (PC) patients; however, for non-<i>BRCA1/2</i> genes, the clinical utility is unclear. A comprehensive multi-gene assessment in unselected Italian PC patients is missing. We evaluated the prevalence and impact of Pathogenic Variants (PV) in 51 PC susceptibility genes in a real-world series of 422 Italian PC patients unselected for Family History (FH), compared the clinical characteristics and conducted survival analyses. 17% of patients had PVs (70/422), mainly in <i>BRCA1/2</i> (4.5%, all <70 y), <i>CDKN2A</i> (4.5%, all >50 y), ATM (2.1%). PV carriers were younger (64 vs. 67; <i>p</i> = 0.02) and had more frequent personal/FH of PC, melanoma and breast/ovarian cancer (all <i>p</i> < 0.05). The Overall Survival (OS) was longer in patients carrying PVs (HR 0.78; <i>p</i> = 0.090), comprising <i>ATM</i> carriers (HR 0.33; <i>p</i> = 0.054). In the oxaliplatin-treated subset, PV carriers showed better control of the disease, although this was not statistically significant (67% vs. 56%). CDKN2A, BRCA2 and ATM were the most frequently altered genes. <i>ATM</i> PVs were positively associated with OS in 41% of PV carriers, 60% of whom carried <i>CDKN2A,</i><i>BRCA2</i> or <i>ATM</i> PVs, had negative FH and would have been missed by traditional referral. Thus, <i>CDKN2A</i> and <i>ATM</i> should be added to <i>BRCA1/2</i> testing regardless of FH. |
| first_indexed | 2024-03-10T00:29:23Z |
| format | Article |
| id | doaj.art-3b4ba054adaf4c88980d262ee3f8bd55 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:29:23Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3b4ba054adaf4c88980d262ee3f8bd552023-11-23T15:27:25ZengMDPI AGCancers2072-66942022-09-011418444710.3390/cancers14184447Clinical Significance of Germline Pathogenic Variants among 51 Cancer Predisposition Genes in an Unselected Cohort of Italian Pancreatic Cancer PatientsAlberto Puccini0Marta Ponzano1Bruna Dalmasso2Irene Vanni3Annalice Gandini4Silvia Puglisi5Roberto Borea6Malvina Cremante7William Bruno8Virginia Andreotti9Eleonora Allavena10Valentino Martelli11Fabio Catalano12Massimiliano Grassi13Maria Laura Iaia14Chiara Pirrone15Alessandro Pastorino16Giuseppe Fornarini17Stefania Sciallero18Paola Ghiorzo19Lorenza Pastorino20Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyDepartment of Health Sciences (DISSAL), University of Genova, 16132 Genova, ItalyGenetics of Rare Cancers, IRCCS Ospedale Policlinico San Martino, L.go Rosanna Benzi X, 16132 Genoa, ItalyDepartment of Internal Medicine and Medical Specialties (DiMI), University of Genoa, V.le Benedetto XV 6, 16132 Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyDepartment of Internal Medicine and Medical Specialties (DiMI), University of Genoa, V.le Benedetto XV 6, 16132 Genoa, ItalyGenetics of Rare Cancers, IRCCS Ospedale Policlinico San Martino, L.go Rosanna Benzi X, 16132 Genoa, ItalyDepartment of Internal Medicine and Medical Specialties (DiMI), University of Genoa, V.le Benedetto XV 6, 16132 Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyDepartment of Internal Medicine and Medical Specialties (DiMI), University of Genoa, V.le Benedetto XV 6, 16132 Genoa, ItalyDepartment of Internal Medicine and Medical Specialties (DiMI), University of Genoa, V.le Benedetto XV 6, 16132 Genoa, ItalyMultigene germline panel testing is recommended for Pancreatic Cancer (PC) patients; however, for non-<i>BRCA1/2</i> genes, the clinical utility is unclear. A comprehensive multi-gene assessment in unselected Italian PC patients is missing. We evaluated the prevalence and impact of Pathogenic Variants (PV) in 51 PC susceptibility genes in a real-world series of 422 Italian PC patients unselected for Family History (FH), compared the clinical characteristics and conducted survival analyses. 17% of patients had PVs (70/422), mainly in <i>BRCA1/2</i> (4.5%, all <70 y), <i>CDKN2A</i> (4.5%, all >50 y), ATM (2.1%). PV carriers were younger (64 vs. 67; <i>p</i> = 0.02) and had more frequent personal/FH of PC, melanoma and breast/ovarian cancer (all <i>p</i> < 0.05). The Overall Survival (OS) was longer in patients carrying PVs (HR 0.78; <i>p</i> = 0.090), comprising <i>ATM</i> carriers (HR 0.33; <i>p</i> = 0.054). In the oxaliplatin-treated subset, PV carriers showed better control of the disease, although this was not statistically significant (67% vs. 56%). CDKN2A, BRCA2 and ATM were the most frequently altered genes. <i>ATM</i> PVs were positively associated with OS in 41% of PV carriers, 60% of whom carried <i>CDKN2A,</i><i>BRCA2</i> or <i>ATM</i> PVs, had negative FH and would have been missed by traditional referral. Thus, <i>CDKN2A</i> and <i>ATM</i> should be added to <i>BRCA1/2</i> testing regardless of FH.https://www.mdpi.com/2072-6694/14/18/4447pancreatic cancergeneticsDNA Damage Repair—Homologous Recombination Deficiency (DDR-HRD)hereditary cancer syndromesgermlinemultigene panel testing |
| spellingShingle | Alberto Puccini Marta Ponzano Bruna Dalmasso Irene Vanni Annalice Gandini Silvia Puglisi Roberto Borea Malvina Cremante William Bruno Virginia Andreotti Eleonora Allavena Valentino Martelli Fabio Catalano Massimiliano Grassi Maria Laura Iaia Chiara Pirrone Alessandro Pastorino Giuseppe Fornarini Stefania Sciallero Paola Ghiorzo Lorenza Pastorino Clinical Significance of Germline Pathogenic Variants among 51 Cancer Predisposition Genes in an Unselected Cohort of Italian Pancreatic Cancer Patients Cancers pancreatic cancer genetics DNA Damage Repair—Homologous Recombination Deficiency (DDR-HRD) hereditary cancer syndromes germline multigene panel testing |
| title | Clinical Significance of Germline Pathogenic Variants among 51 Cancer Predisposition Genes in an Unselected Cohort of Italian Pancreatic Cancer Patients |
| title_full | Clinical Significance of Germline Pathogenic Variants among 51 Cancer Predisposition Genes in an Unselected Cohort of Italian Pancreatic Cancer Patients |
| title_fullStr | Clinical Significance of Germline Pathogenic Variants among 51 Cancer Predisposition Genes in an Unselected Cohort of Italian Pancreatic Cancer Patients |
| title_full_unstemmed | Clinical Significance of Germline Pathogenic Variants among 51 Cancer Predisposition Genes in an Unselected Cohort of Italian Pancreatic Cancer Patients |
| title_short | Clinical Significance of Germline Pathogenic Variants among 51 Cancer Predisposition Genes in an Unselected Cohort of Italian Pancreatic Cancer Patients |
| title_sort | clinical significance of germline pathogenic variants among 51 cancer predisposition genes in an unselected cohort of italian pancreatic cancer patients |
| topic | pancreatic cancer genetics DNA Damage Repair—Homologous Recombination Deficiency (DDR-HRD) hereditary cancer syndromes germline multigene panel testing |
| url | https://www.mdpi.com/2072-6694/14/18/4447 |
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