Frontiers in Oncology (May 2021)
Exome Sequencing in BRCA1-2 Candidate Familias: The Contribution of Other Cancer Susceptibility Genes
- 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
Affiliations
- Gabriella Doddato
- Medical Genetics, University of Siena, Siena, Italy
- Gabriella Doddato
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Floriana Valentino
- Medical Genetics, University of Siena, Siena, Italy
- Floriana Valentino
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Annarita Giliberti
- Medical Genetics, University of Siena, Siena, Italy
- Annarita Giliberti
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Filomena Tiziana Papa
- Medical Genetics, University of Siena, Siena, Italy
- Filomena Tiziana Papa
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Rossella Tita
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Lucia Pia Bruno
- Medical Genetics, University of Siena, Siena, Italy
- Lucia Pia Bruno
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Sara Resciniti
- Medical Genetics, University of Siena, Siena, Italy
- Sara Resciniti
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Chiara Fallerini
- Medical Genetics, University of Siena, Siena, Italy
- Chiara Fallerini
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Elisa Benetti
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Maria Palmieri
- Medical Genetics, University of Siena, Siena, Italy
- Maria Palmieri
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Maria Antonietta Mencarelli
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Alessandra Fabbiani
- Medical Genetics, University of Siena, Siena, Italy
- Alessandra Fabbiani
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Alessandra Fabbiani
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Mirella Bruttini
- Medical Genetics, University of Siena, Siena, Italy
- Mirella Bruttini
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Alfredo Orrico
- Molecular Diagnosis and Characterization of Pathogenic Mechanisms of Rare Genetic Diseases, Azienda Ospedaliera Universitaria Senese and Clinical Genetics, ASL Toscana SudEst. Ospedale della Misericordia, Grosseto, Italy
- Margherita Baldassarri
- Medical Genetics, University of Siena, Siena, Italy
- Margherita Baldassarri
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Francesca Fava
- Medical Genetics, University of Siena, Siena, Italy
- Francesca Fava
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Francesca Fava
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Diego Lopergolo
- Medical Genetics, University of Siena, Siena, Italy
- Diego Lopergolo
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Diego Lopergolo
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Caterina Lo Rizzo
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Vittoria Lamacchia
- Medical Genetics, University of Siena, Siena, Italy
- Vittoria Lamacchia
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Vittoria Lamacchia
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Sara Mannucci
- Medical Genetics, University of Siena, Siena, Italy
- Sara Mannucci
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Sara Mannucci
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Anna Maria Pinto
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Aurora Currò
- Medical Genetics, University of Siena, Siena, Italy
- Aurora Currò
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Aurora Currò
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Virginia Mancini
- Unit of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy
- Oncologic Multidisciplinary Team, Azienda Ospedaliera Universitaria Senese
- Oncologic Multidisciplinary Team, Azienda Usl Toscana Sud Est
- Francesca Mari
- Medical Genetics, University of Siena, Siena, Italy
- Francesca Mari
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Francesca Mari
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Alessandra Renieri
- Medical Genetics, University of Siena, Siena, Italy
- Alessandra Renieri
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Alessandra Renieri
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Francesca Ariani
- Medical Genetics, University of Siena, Siena, Italy
- Francesca Ariani
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Francesca Ariani
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- 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
- DOI
- https://doi.org/10.3389/fonc.2021.649435
- Journal volume & issue
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Vol. 11
Abstract
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.
Keywords
