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Minigene splicing assays identify 20 spliceogenic variants of the breast/Ovarian cancer susceptibility gene RAD51C
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname, Cancers; Volume 14; Issue 12; Pages: 2960
- Publication Year :
- 2022
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2022.
-
Abstract
- RAD51C loss-of-function variants are associated with an increased risk of breast and ovarian cancers. Likewise, splicing disruptions are a frequent mechanism of gene inactivation. Taking advantage of a previous splicing-reporter minigene with exons 2-8 (mgR51C_ex2-8), we proceeded to check its impact on the splicing of candidate ClinVar variants. A total of 141 RAD51C variants at the intron/exon boundaries were analyzed with MaxEntScan. Twenty variants were selected and genetically engineered into the wild-type minigene. All the variants disrupted splicing, and 18 induced major splicing anomalies without any trace or minimal amounts (<br />The EAV lab is supported by grants from the Spanish Ministry of Science and Innovation, Plan Nacional de I+D+I 2013–2016, ISCIII (PI17/00227 and PI20/00225), co-funded by FEDER (the European Regional Development Fund, European Union) and the Consejería de Educación, Junta de Castilla y León, ref. CSI242P18 (actuación cofinanciada P.O. FEDER 2014–2020 de Castilla y León) and Programa Estratégico Instituto de Biología y Genética Molecular (IBGM), Escalera de Excelencia, Junta de Castilla y León (Ref. CLU-2019-02). The MdlH lab is supported by a grant from the Spanish Ministry of Science and Innovation, Plan Nacional de I+D+I 2013–2016, ISCIII (PI20/00110), cofunded by FEDER. LS-M is supported by a predoctoral fellowship from the AECC Scientific Foundation, Sede Provincial de Valladolid (2019–2023). EB-M is a postdoctoral researcher funded by the University of Valladolid (POSTDOC-UVA05, 2022–2025). IL-B is supported by a predoctoral fellowship from the Consejería de Educación, Junta de Castilla y León (2018–2022). AE-S is supported through the Operational Program for Youth Employment and the Youth Employment Initiative (YEI), set up by the Community of Madrid in 2020 and co-financed by the European Social Fund.
- Subjects :
- Cancer Research
Oncology
RAD51C
Hereditary breast and ovarian cancer
Minigenes
Cancer susceptibility genes
hereditary breast and ovarian cancer
cancer susceptibility genes
aberrant splicing
functional assay
minigenes
clinical interpretation
Functional assay
Aberrant splicing
Clinical interpretation
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname, Cancers; Volume 14; Issue 12; Pages: 2960
- Accession number :
- edsair.doi.dedup.....a08efc1652da86ebe3076a3520d43f79