Identification of hereditary breast and ovarian cancer germline variants in Granada (Spain): NGS perspective
Metadatos
Mostrar el registro completo del ítemAutor
Molina Zayas, María; Garrido Navas, María del Carmen; García Puche, José Luis; Pedrinaci, Susana; Martínez Atienza, Margarita; García Linares, Susana; Haro Muñoz, Tomás de; Lorente Acosta, José Antonio; Serrano Fernández, María José; Poyatos Andújar, AntonioEditorial
Springer
Materia
Hereditary breast and ovarian cancer (HBOC) BRCA1 BRCA2 NGS Multigene panel
Fecha
2022-04-22Referencia bibliográfica
Molina-Zayas, M... [et al.]. Identification of hereditary breast and ovarian cancer germline variants in Granada (Spain): NGS perspective. Mol Genet Genomics (2022). [https://doi.org/10.1007/s00438-022-01891-5]
Patrocinador
Universidad de Granada/CBUA; 2018 AEFA Post-residency Grant (Spanish Association of Clinical Laboratory); Ministry of Economy, Competitiveness, Enterprises and Universities DOC_01682Resumen
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.