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- Title
Whole Exome Sequencing in BRCA1-2 Candidate Families: The Contribution of Other Cancer Susceptibility Genes.
- Authors
Doddato, Gabriella; Valentino, Floriana; Giliberti, Annarita; Papa, Filomena Tiziana; Tita, Rossella; Bruno, Lucia Pia; Resciniti, Sara; Fallerini, Chiara; Benetti, Elisa; Palmieri, Maria; Mencarelli, Maria Antonietta; Fabbiani, Alessandra; Bruttini, Mirella; Orrico, Alfredo; Baldassarri, Margherita; Fava, Francesca; Lopergolo, Diego; Lo Rizzo, Caterina; Lamacchia, Vittoria; Mannucci, Sara
- 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 Whole Exome Sequencing (WES) 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. Whole 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.
- Subjects
NATIONAL Comprehensive Cancer Network (U.S.); CANCER genes; CANCER susceptibility; GENETIC testing; OVARIAN cancer; BREAST cancer
- Publication
Frontiers in Oncology, 2021, Vol 11, pN.PAG
- ISSN
2234-943X
- Publication type
Article
- DOI
10.3389/fonc.2021.649435