Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/230612
COMPARTIR / EXPORTAR:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE

Invitar a revisión por pares abierta
Título

Comprehensive Functional Characterization and Clinical Interpretation of 20 Splice-Site Variants of the RAD51C Gene

AutorSanoguera-Miralles, Lara CSIC ORCID CVN; Valenzuela-Palomo, Alberto CSIC; Bueno-Martínez, Elena CSIC ORCID CVN; Llovet, Patricia; Díez-Gómez, Beatriz CSIC; Caloca, María J. CSIC ORCID CVN; Pérez-Segura, Pedro; Fraile-Bethencourt, Eugenia CSIC ORCID; Colmena, Marta; Carvalho, Sara; Allen, Jamie; Easton, Douglas F.; Devilee, Peter; Vreeswijk, Maaike P. G.; Hoya, Miguel de la; Velasco, Eladio CSIC ORCID
Palabras claveBreast cancer
Ovarian cancer
Susceptibility genes
RAD51C
Genetic variants
Splicing
Aberrant splicing
VUS
Functional assay
Minigene
Clinical interpretation
Fecha de publicación2020
EditorMultidisciplinary Digital Publishing Institute
CitaciónCancers 12(12): 3771 (2020)
ResumenHereditary breast and/or ovarian cancer is a highly heterogeneous disease with more than 10 known disease-associated genes. In the framework of the BRIDGES project (Breast Cancer Risk after Diagnostic Gene Sequencing), the RAD51C gene has been sequenced in 60,466 breast cancer patients and 53,461 controls. We aimed at functionally characterizing all the identified genetic variants that are predicted to disrupt the splicing process. Forty RAD51C variants of the intron-exon boundaries were bioinformatically analyzed, 20 of which were selected for splicing functional assays. To test them, a splicing reporter minigene with exons 2 to 8 was designed and constructed. This minigene generated a full-length transcript of the expected size (1062 nucleotides), sequence, and structure (Vector exon V1- RAD51C exons_2-8- Vector exon V2). The 20 candidate variants were genetically engineered into the wild type minigene and functionally assayed in MCF-7 cells. Nineteen variants (95%) impaired splicing, while 18 of them produced severe splicing anomalies. At least 35 transcripts were generated by the mutant minigenes: 16 protein-truncating, 6 in-frame, and 13 minor uncharacterized isoforms. According to ACMG/AMP-based standards, 15 variants could be classified as pathogenic or likely pathogenic variants: c.404G > A, c.405-6T > A, c.571 + 4A > G, c.571 + 5G > A, c.572-1G > T, c.705G > T, c.706-2A > C, c.706-2A > G, c.837 + 2T > C, c.905-3C > G, c.905-2A > C, c.905-2_905-1del, c.965 + 5G > A, c.1026 + 5_1026 + 7del, and c.1026 + 5G > T.
Descripción© 2020 by the authors.
Versión del editorhttp://dx.doi.org/10.3390/cancers12123771
URIhttp://hdl.handle.net/10261/230612
DOI10.3390/cancers12123771
E-ISSN2072-6694
Aparece en las colecciones: (IBGM) Artículos




Ficheros en este ítem:
Fichero Descripción Tamaño Formato
Comprehensive_Sanoguera_Art2020.pdf1,86 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo

CORE Recommender

PubMed Central
Citations

8
checked on 17-mar-2024

SCOPUSTM   
Citations

11
checked on 21-mar-2024

WEB OF SCIENCETM
Citations

11
checked on 24-feb-2024

Page view(s)

122
checked on 28-mar-2024

Download(s)

114
checked on 28-mar-2024

Google ScholarTM

Check

Altmetric

Altmetric


Artículos relacionados:


Este item está licenciado bajo una Licencia Creative Commons Creative Commons