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Recurrent genetic variants and prioritization of variants of uncertain clinical significance associated with hereditary breast and ovarian cancer in families from the Region of Murcia

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dc.contributor.authorRosado-Jiménez, Laura
dc.contributor.authorMestre-Terkemani, Younes
dc.contributor.authorGarcía-Aliaga, Ángeles
dc.contributor.authorMarín-Vera, Miguel
dc.contributor.authorMacías-Cerrolaza, José Antonio
dc.contributor.authorGarcía-Hernández, María Rosario
dc.contributor.authorZafra-Poves, Marta
dc.contributor.authorSánchez-Henarejos, Pilar
dc.contributor.authorAyala de la Peña, Francisco
dc.contributor.authorAlonso-Romero, José Luis
dc.contributor.authorNoguera Velasco, José Antonio
dc.contributor.authorRuiz Espejo, Francisco
dc.contributor.authorSarabia Meseguer, María Desamparados
dc.contributor.departmentMedicina
dc.date.accessioned2024-11-05T12:04:32Z
dc.date.available2024-11-05T12:04:32Z
dc.date.issued2023-09-22
dc.description© 2023 the author(s). This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in Advances in Laboratory Medicine. To access the final edited and published work see https://doi.org/10.1515/almed-2023-0103
dc.description.abstractObjectives Hereditary breast and ovarian cancer (HBOC) follows an autosomal dominant inheritance pattern of cancer susceptibility genes. The risk of developing this disease is primarily associated with germline mutations in the BRCA1 and BRCA2 genes. The advent of massive genetic sequencing technologies has expanded the mutational spectrum of this hereditary syndrome, thereby increasing the number of variants of uncertain clinical significance (VUS) detected by genetic testing. Methods A prevalence study of HBOC was performed within 2,928 families from the Region of Murcia, in southeastern Spain. Genetic testing enabled the identification of recurrent pathogenic variants and founder mutations, which were mainly related to the BRCA1 and BRCA2 genes. VUS testing was performed using a prioritization algorithm designed by our working group. Results Variants c.68_69del, c.212+1G>A, and c.5123C>A were detected in 30 % of BRCA1 carriers, whereas exon 2 deletion concurrent with c.3264dupT, c.3455T>G and c.9117G>A variants were found in 30 % of BRCA2 carriers. A total of 16 VUS (15 %) were prioritized. Conclusions The genotype-phenotype correlation observed in our study is consistent with the scientific literature. Furthermore, the founder effect of c.1918C>T (BRCA1) and c.8251_8254del (ATM) was verified in the Murcian population, whereas exon 2 deletion (BRCA2) was proven to be a Spanish founder mutation. Our algorithm enabled us to prioritize potentially pathogenic VUS that required further testing to determine their clinical significance and potential role in HBOC.es
dc.formatapplication/pdfes
dc.format.extent9es
dc.identifier.citationAdv Lab Med 2023 4(3): 279–287
dc.identifier.doihttps://doi.org/10.1515/almed-2023-0103
dc.identifier.issn2628-491X
dc.identifier.urihttp://hdl.handle.net/10201/145995
dc.languageenges
dc.publisherDe Gruyter
dc.relationSin financiación externa a la Universidades
dc.relation.publisherversionhttps://www.degruyter.com/document/doi/10.1515/almed-2023-0103/html#MLA
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectFounder effectes
dc.subjectMutational spectrumes
dc.subjectPrioritizationes
dc.subjectHereditary breast and ovarian canceres
dc.subjectVariants of uncertain clinical significancees
dc.subjectRecurrent pathogenic variantses
dc.titleRecurrent genetic variants and prioritization of variants of uncertain clinical significance associated with hereditary breast and ovarian cancer in families from the Region of Murciaes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublicationf3810358-f28e-4db9-88fb-457b1c3f4a1f
relation.isAuthorOfPublication0df35bdc-c7fd-417d-9e50-b1b69e17c1ea
relation.isAuthorOfPublication4ca8b838-1db9-4ced-ade1-e3e992f18143
relation.isAuthorOfPublication.latestForDiscoveryf3810358-f28e-4db9-88fb-457b1c3f4a1f
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