000133172 001__ 133172
000133172 005__ 20240322140241.0
000133172 0247_ $$2doi$$a10.3389/fgene.2023.1274108
000133172 0248_ $$2sideral$$a137889
000133172 037__ $$aART-2024-137889
000133172 041__ $$aeng
000133172 100__ $$aAlonso, Natalia
000133172 245__ $$aAssociation between missense variants of uncertain significance in the CHEK2 gene and hereditary breast cancer: a cosegregation and bioinformatics analysis
000133172 260__ $$c2024
000133172 5060_ $$aAccess copy available to the general public$$fUnrestricted
000133172 5203_ $$aInherited mutations in the CHEK2 gene have been associated with an increased lifetime risk of developing breast cancer (BC). We aim to identify in the study population the prevalence of mutations in the CHEK2 gene in diagnosed BC patients, evaluate the phenotypic characteristics of the tumor and family history, and predict the deleteriousness of the variants of uncertain significance (VUS). A genetic study was performed, from May 2016 to April 2020, in 396 patients diagnosed with BC at the University Hospital Lozano Blesa of Zaragoza, Spain. Patients with a genetic variant in the CHEK2 gene were selected for the study. We performed a descriptive analysis of the clinical variables, a bibliographic review of the variants, and a cosegregation study when possible. Moreover, an in-depth bioinformatics analysis of CHEK2 VUS was carried out. We identified nine genetic variants in the CHEK2 gene in 10 patients (two pathogenic variants and seven VUS). This supposes a prevalence of 0.75% and 1.77%, respectively. In all cases, there was a family history of BC in first- and/or second-degree relatives. We carried out a cosegregation study in two families, being positive in one of them. The bioinformatics analyses predicted the pathogenicity of six of the VUS. In conclusion, CHEK2 mutations have been associated with an increased risk for BC. This risk is well-established for foundation variants. However, the risk assessment for other variants is unclear. The incorporation of bioinformatics analysis provided supporting evidence of the pathogenicity of VUS.
000133172 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E45-23R$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-107293GB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2022-141068NB-I00
000133172 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000133172 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000133172 700__ $$0(orcid)0000-0002-1817-4549$$aMenao, Sebastián$$uUniversidad de Zaragoza
000133172 700__ $$aLastra, Rodrigo
000133172 700__ $$0(orcid)0000-0002-9336-1563$$aArruebo, María
000133172 700__ $$aBueso, María P.
000133172 700__ $$aPérez, Esther
000133172 700__ $$aMurillo, M. Laura
000133172 700__ $$aÁlvarez, María
000133172 700__ $$aAlonso, Alba
000133172 700__ $$aRebollar, Soraya
000133172 700__ $$aCruellas, Mara
000133172 700__ $$0(orcid)0000-0002-3592-820X$$aArribas, Dolores$$uUniversidad de Zaragoza
000133172 700__ $$aRamos, Mónica$$uUniversidad de Zaragoza
000133172 700__ $$aIsla, Dolores
000133172 700__ $$0(orcid)0000-0002-1896-7805$$aGalano-Frutos, Juan José$$uUniversidad de Zaragoza
000133172 700__ $$0(orcid)0000-0002-9590-7371$$aGarcía-Cebollada, Helena$$uUniversidad de Zaragoza
000133172 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, Javier$$uUniversidad de Zaragoza
000133172 700__ $$0(orcid)0000-0003-0123-4274$$aAndrés, Raquel$$uUniversidad de Zaragoza
000133172 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000133172 7102_ $$11013$$2090$$aUniversidad de Zaragoza$$bDpto. Cirugía$$cÁrea Cirugía
000133172 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000133172 7102_ $$11002$$2807$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Toxicología
000133172 773__ $$g14 (2024), 1274108 [16 pp.]$$pFront. genet.$$tFrontiers in Genetics$$x1664-8021
000133172 8564_ $$s1975510$$uhttps://zaguan.unizar.es/record/133172/files/texto_completo.pdf$$yVersión publicada
000133172 8564_ $$s2302345$$uhttps://zaguan.unizar.es/record/133172/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000133172 909CO $$ooai:zaguan.unizar.es:133172$$particulos$$pdriver
000133172 951__ $$a2024-03-22-12:45:07
000133172 980__ $$aARTICLE