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Germline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patients

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dc.creatorSierra‑Díaz, Diana Carolinaspa
dc.creatorMorel, Adrien spa
dc.creatorFonseca Mendoza, Dora Janethspa
dc.creatorContreras Bravo, Noraspa
dc.creatorMolano González, Nicolásspa
dc.creatorBorras, Marianaspa
dc.creatorMunevar, Isabelspa
dc.creatorLema, Mauriciospa
dc.creatorIdrobo, Henryspa
dc.creatorTrujillo, Danielaspa
dc.creatorSerrano, Normaspa
dc.creatorOrduz, Ana Isabelspa
dc.creatorLopera, Diegospa
dc.creatorGonzález, Jaimespa
dc.creatorRojas, Gustavospa
dc.creatorLondono-De Los Ríos, Paulaspa
dc.creatorManneh, Rayspa
dc.creatorCabrera Pérez, Rodrigospa
dc.creatorRubiano, Wilsonspa
dc.creatorde la Peña, Jairospa
dc.date.accessioned2025-01-26T18:30:39Z
dc.date.available2025-01-26T18:30:39Z
dc.date.created2024-12-01spa
dc.date.issued2024-12-01spa
dc.descriptionBackground: In Colombia and worldwide, breast cancer (BC) is the most frequently diagnosed neoplasia and the leading cause of death from cancer among women. Studies predominantly involve hereditary and familial cases, demonstrating a gap in the literature regarding the identification of germline mutations in unselected patients from Latin-America. Identification of pathogenic/likely pathogenic (P/LP) variants is important for shaping national genetic analysis policies, genetic counseling, and early detection strategies. The present study included 400 women with unselected breast cancer (BC), in whom we analyzed ten genes, using Whole Exome Sequencing (WES), know to confer risk for BC, with the aim of determining the genomic profile of previously unreported P/LP variants in the affected population. Additionally, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to identify Large Genomic Rearrangements (LGRs) in the BRCA1/2 genes. To ascertain the functional impact of a recurrent intronic variant (ATM c.5496 + 2_5496 + 5delTAAG), a minigene assay was conducted. Results: We ascertained the frequency of P/LP germline variants in BRCA2 (2.5%), ATM (1.25%), BRCA1 (0.75%), PALB2 (0.50%), CHEK2 (0.50%), BARD1 (0.25%), and RAD51D (0.25%) genes in the population of study. P/LP variants account for 6% of the total population analyzed. No LGRs were detected in our study. We identified 1.75% of recurrent variants in BRCA2 and ATM genes. One of them corresponds to the ATM c.5496 + 2_5496 + 5delTAAG. Functional validation of this variant demonstrated a splicing alteration probably modifying the Pincer domain and subsequent protein structure. Conclusion: This study described for the first time the genomic profile of ten risk genes in Colombian women with unselected BC. Our findings underscore the significance of population-based research, advocating the consideration of molecular testing in all women with cancer.spa
dc.format.mimetypeapplication/pdfspa
dc.identifier.doihttps://doi.org/10.1186/s40246-024-00623-7spa
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/44810
dc.language.isoengspa
dc.publisherHuman Genomicsspa
dc.relation.ispartofHuman Genomicsspa
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccessspa
dc.rights.accesoAbierto (Texto Completo)spa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/spa
dc.sourceHuman Genomicsspa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subjectMolecular Medicinespa
dc.subjectMolecular Biologyspa
dc.subjectGeneticsspa
dc.subjectDrug Discoveryspa
dc.titleGermline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patientsspa
dc.typearticlespa
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersionspa
dc.type.spaArtículospa
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