Exome Sequencing in BRCA1-2 Candidate Familias: The Contribution of Other Cancer Susceptibility Genes
oleh: Gabriella Doddato, Gabriella Doddato, Floriana Valentino, Floriana Valentino, Annarita Giliberti, Annarita Giliberti, Filomena Tiziana Papa, Filomena Tiziana Papa, Rossella Tita, Lucia Pia Bruno, Lucia Pia Bruno, Sara Resciniti, Sara Resciniti, Chiara Fallerini, Chiara Fallerini, Elisa Benetti, Maria Palmieri, Maria Palmieri, Maria Antonietta Mencarelli, Alessandra Fabbiani, Alessandra Fabbiani, Alessandra Fabbiani, Mirella Bruttini, Mirella Bruttini, Alfredo Orrico, Margherita Baldassarri, Margherita Baldassarri, Francesca Fava, Francesca Fava, Francesca Fava, Diego Lopergolo, Diego Lopergolo, Diego Lopergolo, Caterina Lo Rizzo, Vittoria Lamacchia, Vittoria Lamacchia, Vittoria Lamacchia, Sara Mannucci, Sara Mannucci, Sara Mannucci, Anna Maria Pinto, Aurora Currò, Aurora Currò, Aurora Currò, Virginia Mancini, Oncologic Multidisciplinary Team, Azienda Ospedaliera Universitaria Senese, Oncologic Multidisciplinary Team, Azienda Usl Toscana Sud Est, Francesca Mari, Francesca Mari, Francesca Mari, Alessandra Renieri, Alessandra Renieri, Alessandra Renieri, Francesca Ariani, Francesca Ariani, Francesca Ariani, Alessandro Neri, Donato Casella, Andrea Bernini, Stefania Marsili, Roberto Petrioli, Salvatora Tindara Miano, Alessandra Pascucci, Ignazio Martellucci, Monica Crociani, Marta Vannini, Federica Fantozzi, Andrea Stella, Alessia Carmela Tripodi, Angelamaria Giusti, Alfonso Fausto, Lucia Mantovani, Francesca Belardi
| Format: | Article |
|---|---|
| Diterbitkan: | Frontiers Media S.A. 2021-05-01 |
Deskripsi
Hereditary Breast and Ovarian Cancer (HBOC) syndrome is a condition in which the risk of breast and ovarian cancer is higher than in the general population. The prevalent pathogenesis is attributable to inactivating variants of the BRCA1-2 highly penetrant genes, however, other cancer susceptibility genes may also be involved. By Exome Sequencing (ES) we analyzed a series of 200 individuals selected for genetic testing in BRCA1-2 genes according to the updated National Comprehensive Cancer Network (NCCN) guidelines. Analysis by MLPA was performed to detect large BRCA1-2 deletions/duplications. Focusing on BRCA1-2 genes, data analysis identified 11 cases with pathogenic variants (4 in BRCA1 and 7 in BRCA1-2) and 12 with uncertain variants (7 in BRCA1 and 5 in BRCA2). Only one case was found with a large BRCA1 deletion. Exome analysis allowed to characterize pathogenic variants in 21 additional genes: 10 genes more traditionally associated to breast and ovarian cancer (ATM, BRIP1, CDH1, PALB2, PTEN, RAD51C, and TP53) (5% diagnostic yield) and 11 in candidate cancer susceptibility genes (DPYD, ERBB3, ERCC2, MUTYH, NQO2, NTHL1, PARK2, RAD54L, and RNASEL). In conclusion, this study allowed a personalized risk assessment and clinical surveillance in an increased number of HBOC families and to broaden the spectrum of causative variants also to candidate “non-canonical” genes.