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dc.contributor.authorMolina Zayas, María
dc.contributor.authorGarrido Navas, María del Carmen 
dc.contributor.authorGarcía Puche, José Luis 
dc.contributor.authorPedrinaci, Susana
dc.contributor.authorMartínez Atienza, Margarita
dc.contributor.authorGarcía Linares, Susana
dc.contributor.authorHaro Muñoz, Tomás de 
dc.contributor.authorLorente Acosta, José Antonio 
dc.contributor.authorSerrano Fernández, María José 
dc.contributor.authorPoyatos Andújar, Antonio
dc.identifier.citationMolina-Zayas, M... [et al.]. Identification of hereditary breast and ovarian cancer germline variants in Granada (Spain): NGS perspective. Mol Genet Genomics (2022). []es_ES
dc.descriptionFunding for open access charge: Universidad de Granada/CBUA. Maria Molina-Zayas has been a recipient of the 2018 AEFA Post-residency Grant (Spanish Association of Clinical Laboratory) and Dr. Carmen Garrido-Navas holds a postdoctoral fellowship from the Ministry of Economy, Competitiveness, Enterprises and Universities (DOC_01682).es_ES
dc.description.abstractThe 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.es_ES
dc.description.sponsorshipUniversidad de Granada/CBUAes_ES
dc.description.sponsorship2018 AEFA Post-residency Grant (Spanish Association of Clinical Laboratory)es_ES
dc.description.sponsorshipMinistry of Economy, Competitiveness, Enterprises and Universities DOC_01682es_ES
dc.rightsAtribución 3.0 España*
dc.subjectHereditary breast and ovarian cancer (HBOC)es_ES
dc.subjectMultigene paneles_ES
dc.titleIdentification of hereditary breast and ovarian cancer germline variants in Granada (Spain): NGS perspectivees_ES

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Atribución 3.0 España
Except where otherwise noted, this item's license is described as Atribución 3.0 España