Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge
| Autor: | A. Dimino, Lidia Rita Corsini, A. Cucinella, D. Cancelliere, Fiorella Guadagni, Valentina Calò, G. Madonia, Chiara Brando, E. Pedone, Viviana Bazan, Lorena Incorvaia, Daniele Fanale, A. Russo, Marco Bono, A. Fiorino, R. Scalia, Giuseppe Badalamenti, Clarissa Filorizzo, Nadia Barraco |
|---|---|
| Přispěvatelé: | Bono M., Fanale D., Incorvaia L., Cancelliere D., Fiorino A., Calo V., Dimino A., Filorizzo C., Corsini L.R., Brando C., Madonia G., Cucinella A., Scalia R., Barraco N., Guadagni F., Pedone E., Badalamenti G., Russo A., Bazan V. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Settore MED/06 - Oncologia Medica PALB2 pancreatic cancer Breast Neoplasms Breast cancer breast cancer MUTYH Internal medicine Pancreatic cancer Medicine Humans Genetic Predisposition to Disease Genetic Testing Family history CHEK2 Original Research Genetic testing Ovarian Neoplasms medicine.diagnostic_test business.industry BRCA1 Protein Cancer medicine.disease Pancreatic Neoplasms ovarian cancer multi-gene panel testing Female germline pathogenic variants business |
| Zdroj: | ESMO Open |
| Popis: | 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. Highlights • Patients with significant personal and/or family history of BC, OC, or PC could benefit from a multi-gene panel testing. • A total of 205 out of 915 BRCA1/2-wt BC, OC, or PC patients were genetically tested for germline PVs/LPVs in other genes. • A total of 15.1% of 205 BC, OC, or PC patients harboured germline PVs/LPVs in cancer susceptibility genes different from BRCA1/2. • PALB2, CHEK2, ATM, and RAD51C have been shown to be the genes more frequently altered in BRCA1/2-wt patients. • Using a multi-gene panel testing could improve the clinical management of patients and their unaffected family members. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|