RT Journal Article
T1 Identification of hereditary breast and ovarian cancer germline variants in Granada (Spain): NGS perspective.
A1 Molina-Zayas, Maria
A1 Garrido-Navas, Carmen
A1 Garcia-Puche, Jose Luis
A1 Barwell, Julian
A1 Pedrinaci, Susana
A1 Atienza, Margarita Martinez
A1 Garcia-Linares, Susana
A1 de Haro-Muñoz, Tomas
A1 Lorente, Jose Antonio
A1 Serrano, M Jose
A1 Poyatos-Andujar, Antonio
K1 BRCA1
K1 BRCA2
K1 Hereditary breast and ovarian cancer (HBOC)
K1 Multigene panel
K1 NGS
AB The aim of this study was to assess the prevalence of germline variants in cancer-predisposing genes by either targeted (BRCA1/2) or multigene NGS panel in a high-risk Hereditary Breast and Ovarian Cancer (HBOC) cohort. Samples from 824 Caucasian probands were retrospectively collected and the impact of genetic diagnosis and genetic variants epidemiology in this cohort was evaluated. Performance of risk-reducing prophylactic measures, such as prophylactic mastectomy and/or prophylactic oophorectomy, was assessed through clinical follow-up of patients with a positive genetic result. Pathogenic variants predisposing to HBOC were identified in 11.9% (98/824) individuals at BRCA2 (47/98), BRCA1 (24/98), PALB2 (8/51), ATM (7/51), CHEK2 (6/51) MSH6, (2/51), RAD51C (2/51) and TP53 (2/386). Of them, 11 novel pathogenic variants and 12 VUS were identified, characterized, and submitted to ClinVar. Regarding clinical impact, the risk of developing basal or Her2 breast cancer was increased 15.7 times or 37.5 times for BRCA1 and MSH6 pathogenic variants respectively. On the contrary, the risk of developing basal or luminal A breast cancer was reduced to 81% or 77% for BRCA2 and BRCA1 pathogenic variants, respectively. Finally, 53.2% of individuals testing positive for class IV/V variants underwent prophylactic surgery (mastectomy, oophorectomy or both) being significantly younger at the cancer diagnosis than those undertaking prophylactic measures (p = 0.008). Of them, 8 carried a pathogenic/likely pathogenic variant in other genes different from BRCA1 and BRCA2, and the remaining (46.7%) decided to continue with clinical follow-up. No differences in pathogenicity or risk of developing cancer were found for BRCA1/2 between targeted and multigene sequencing strategies; however, NGS was able to resolve a greater proportion of high-risk patients.
PB Springer
YR 2022
FD 2022-03-23
LK http://hdl.handle.net/10668/20230
UL http://hdl.handle.net/10668/20230
LA en
NO Molina-Zayas M, Garrido-Navas C, García-Puche JL, Barwell J, Pedrinaci S, Atienza MM,  et al.  Identification of hereditary breast and ovarian cancer germline variants in Granada (Spain): NGS perspective. Mol Genet Genomics. 2022 May;297(3):859-871.
DS RISalud
RD Apr 6, 2025