Targeted RNA-seq successfully identifies normal and pathogenic splicing events in breast/ovarian cancer susceptibility and Lynch syndrome genes
![Thumbnail](/xmlui/themes/Mirage2//images/thumbnails/thumn_cientif.png)
Identificadores![](/xmlui/themes/Mirage2//images/despl_identif.png)
Identificadores
Visualización o descarga de ficheros![](/xmlui/themes/Mirage2//images/despl_contenidos.png)
Visualización o descarga de ficheros
Autor corporativo
K. ConFaB InvestigatorsFecha de publicación
2019Título de revista
INTERNATIONAL JOURNAL OF CANCER
Tipo de contenido
Artigo
DeCS
mutación | proteínas de unión al ADN | línea celular | análisis de secuencias | electroforesis | empalme de ARN | humanos | proteína BRCA1 | síndrome hereditario de cáncer de mama y ovario | predisposición genética a la enfermedad | neoplasias colorrectales | proteína BRCA2MeSH
Mutation | DNA-Binding Proteins | Cell Line | Humans | Electrophoresis | BRCA1 Protein | RNA Splicing | Hereditary Breast and Ovarian Cancer Syndrome | BRCA2 Protein | Genetic Predisposition to Disease | Colorectal Neoplasms | Sequence AnalysisResumen
A subset of genetic variants found through screening of patients with hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome impact RNA splicing. Through target enrichment of the transcriptome, it is possible to perform deep-sequencing and to identify the different and even rare mRNA isoforms. A targeted RNA-seq approach was used to analyse the naturally-occurring splicing events for a panel of 8 breast and/or ovarian cancer susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, PTEN, STK11, CDH1, TP53), 3 Lynch syndrome genes (MLH1, MSH2, MSH6) and the fanconi anaemia SLX4 gene, in which monoallelic mutations were found in non-BRCA families. For BRCA1, BRCA2, RAD51C and RAD51D the results were validated by capillary electrophoresis and were compared to a non-targeted RNA-seq approach. We also compared splicing events from lymphoblastoid cell-lines with those from breast and ovarian fimbriae tissues. The potential of targeted RNA-seq to detect pathogenic changes in RNA-splicing was validated by the inclusion of samples with previously well characterized BRCA1/2 genetic variants. In our study, we update the catalogue of normal splicing events for BRCA1/2, provide an extensive catalogue of normal RAD51C and RAD51D alternative splicing, and list splicing events found for eight other genes. Additionally, we show that our approach allowed the identification of aberrant splicing events due to the presence of BRCA1/2 genetic variants and distinguished between complete and partial splicing events. In conclusion, targeted-RNA-seq can be very useful to classify variants based on their putative pathogenic impact on splicing.
Excepto si se señala otra cosa, la licencia del ítem se describe como Atribución-NoComercial 4.0 Internacional
![](/xmlui/themes/Mirage2//images/final_lines.png)