학술논문
Exome Sequencing in BRCA1-2 Candidate Familias: The Contribution of Other Cancer Susceptibility Genes
Document Type
article
Author
Gabriella Doddato; Floriana Valentino; Annarita Giliberti; Filomena Tiziana Papa; Rossella Tita; Lucia Pia Bruno; Sara Resciniti; Chiara Fallerini; Elisa Benetti; Maria Palmieri; Maria Antonietta Mencarelli; Alessandra Fabbiani; Mirella Bruttini; Alfredo Orrico; Margherita Baldassarri; Francesca Fava; Diego Lopergolo; Caterina Lo Rizzo; Vittoria Lamacchia; Sara Mannucci; Anna Maria Pinto; Aurora Currò; Virginia Mancini; Oncologic Multidisciplinary Team, Azienda Ospedaliera Universitaria Senese; Oncologic Multidisciplinary Team, Azienda Usl Toscana Sud Est; Francesca Mari; Alessandra Renieri; 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
Source
Frontiers in Oncology, Vol 11 (2021)
Subject
Language
English
ISSN
2234-943X
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.