M Bono1, D Fanale1, L Incorvaia2, D Cancelliere1, A Fiorino1, V Calò1, A Dimino1, C Filorizzo1, L R Corsini1, C Brando1, G Madonia1, A Cucinella1, R Scalia1, N Barraco1, F Guadagni3, E Pedone1, G Badalamenti1, A Russo4, V Bazan2. 1. Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy. 2. Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Section of Medical Oncology, University of Palermo, Palermo, Italy. 3. BioBIM (Interinstitutional Multidisciplinary Biobank), IRCCS San Raffaele Pisana, Rome, Italy; Department of Human Sciences & Quality of Life Promotion, San Raffaele Roma Open University, Rome, Italy. 4. Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy. Electronic address: antonio.russo@usa.net.
Abstract
BACKGROUND: Hereditary breast cancer (BC), ovarian cancer (OC), and pancreatic cancer (PC) are the major BRCA-associated tumours. However, some BRCA1/2-wild-type (wt) patients with a strong personal and/or family history of cancer need a further genetic testing through a multi-gene panel containing other high- and moderate-risk susceptibility genes. PATIENTS AND METHODS: Our study was aimed to assess if some BC, OC, or PC patients should be offered multi-gene panel testing, based on well-defined criteria concerning their personal and/or family history of cancer, such as earliness of cancer onset, occurrence of multiple tumours, or presence of at least two or more affected first-degree relatives. For this purpose, 205 out of 915 BC, OC, or PC patients, resulted negative for BRCA1/2 and with significant personal and/or family history of cancer, were genetically tested for germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes different from BRCA1/2. RESULTS: Our investigation revealed that 31 (15.1%) out of 205 patients harboured germline PVs/LPVs in no-BRCA genes, including PALB2, CHEK2, ATM, MUTYH, MSH2, and RAD51C. Interestingly, in the absence of an analysis conducted through multi-gene panel, a considerable percentage (15.1%) of PVs/LPVs would have been lost. CONCLUSIONS: Providing a multi-gene panel testing to BRCA1/2-wt BC/OC/PC patients with a strong personal and/or family history of cancer could significantly increase the detection rates of germline PVs/LPVs in other cancer predisposition genes beyond BRCA1/2. The use of a multi-gene panel testing could improve the inherited cancer risk estimation and clinical management of patients and unaffected family members.
BACKGROUND:Hereditary breast cancer (BC), ovarian cancer (OC), and pancreatic cancer (PC) are the major BRCA-associated tumours. However, some BRCA1/2-wild-type (wt) patients with a strong personal and/or family history of cancer need a further genetic testing through a multi-gene panel containing other high- and moderate-risk susceptibility genes. PATIENTS AND METHODS: Our study was aimed to assess if some BC, OC, or PCpatients should be offered multi-gene panel testing, based on well-defined criteria concerning their personal and/or family history of cancer, such as earliness of cancer onset, occurrence of multiple tumours, or presence of at least two or more affected first-degree relatives. For this purpose, 205 out of 915 BC, OC, or PCpatients, resulted negative for BRCA1/2 and with significant personal and/or family history of cancer, were genetically tested for germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes different from BRCA1/2. RESULTS: Our investigation revealed that 31 (15.1%) out of 205 patients harboured germline PVs/LPVs in no-BRCA genes, including PALB2, CHEK2, ATM, MUTYH, MSH2, and RAD51C. Interestingly, in the absence of an analysis conducted through multi-gene panel, a considerable percentage (15.1%) of PVs/LPVs would have been lost. CONCLUSIONS: Providing a multi-gene panel testing to BRCA1/2-wt BC/OC/PCpatients with a strong personal and/or family history of cancer could significantly increase the detection rates of germline PVs/LPVs in other cancer predisposition genes beyond BRCA1/2. The use of a multi-gene panel testing could improve the inherited cancer risk estimation and clinical management of patients and unaffected family members.
Authors: A Russo; L Incorvaia; E Capoluongo; P Tagliaferri; S Gori; L Cortesi; M Genuardi; D Turchetti; U De Giorgi; M Di Maio; M Barberis; M Dessena; M Del Re; A Lapini; C Luchini; B A Jereczek-Fossa; A Sapino; S Cinieri Journal: ESMO Open Date: 2022-05-19
Authors: Valerie Catherine Linz; Amelie Löwe; Josche van der Ven; Annette Hasenburg; Marco Johannes Battista Journal: Front Oncol Date: 2022-08-31 Impact factor: 5.738
Authors: Lauren Turza; Leann A Lovejoy; Clesson E Turner; Craig D Shriver; Rachel E Ellsworth Journal: Front Oncol Date: 2022-08-26 Impact factor: 5.738