ArticleOncogene2002
Pathological splice mutations outside the invariant AG/GT splice sites of BRCA1 exon 5 increase alternative transcript levels in the 5' end of the BRCA1 gene.
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Association of Genomic Domains inCancer research · 2020Article
- BRCA1-No Matter How You Splice It.Cancer research · 2019Review
- Evaluation of relative quantification of alternatively spliced transcripts using droplet digital PCR.Biomolecular detection and quantification · 2017Article
- Adding In Silico Assessment of Potential Splice Aberration to the Integrated Evaluation of BRCA Gene Unclassified Variants.Human mutation · 2016Article
- Increased chromosomal radiosensitivity in asymptomatic carriers of a heterozygous BRCA1 mutation.Breast cancer research : BCR · 2016Article
- Genome-wide analysis of alternative transcripts in human breast cancer.Breast cancer research and treatment · 2015Article
- Functional characterization of BRCA1 gene variants by mini-gene splicing assay.European journal of human genetics : EJHG · 2014Article
- Article
- GT198 Splice Variants Display Dominant-Negative Activities and Are Induced by Inactivating Mutations.Genes & cancer · 2013Article
- Occurrence of GCH1 gene mutations in a group of Indian dystonia patients.Journal of neural transmission (Vienna, Austria : 1996) · 2012Article
- Article
- Contribution of bioinformatics predictions and functional splicing assays to the interpretation of unclassified variants of the BRCA genes.European journal of human genetics : EJHG · 2011Article
- An entire exon 3 germ-line rearrangement in the BRCA2 gene: pathogenic relevance of exon 3 deletion in breast cancer predisposition.BMC medical genetics · 2011Article
- Haplotype and quantitative transcript analyses of Portuguese breast/ovarian cancer families with the BRCA1 R71G founder mutation of Galician origin.Familial cancer · 2009Article
- Prediction and assessment of splicing alterations: implications for clinical testing.Human mutation · 2008Article
- Short/branched-chain acyl-CoA dehydrogenase deficiency due to an IVS3+3A>G mutation that causes exon skipping.Human genetics · 2006Article
- Biased exon/intron distribution of cryptic and de novo 3' splice sites.Nucleic acids research · 2005Article
- Evolutionary conservation analysis increases the colocalization of predicted exonic splicing enhancers in the BRCA1 gene with missense sequence changes and in-frame deletions, but not polymorphisms.Breast cancer research : BCR · 2005Article
- BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families.British journal of cancer · 2004Article
- Emerging roles of BRCA1 alternative splicing.Molecular pathology : MP · 2003Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report two novel mutations in the splice sites of BRCA1 exon 5: IVS5+3A>G, a Belgian founder mutation, and IVS3-6T>G, identified in one family with a strong family history of breast cancer. Real-time RT-PCR showed that IVS3-6T>G leads to a fivefold increase of the BRCA1-Deltaex5 (isoform with an in frame skip of exon 5) ratio to the total BRCA1 expression level. IVS5+3A>G results in a 10-fold increase of the BRCA1-Delta22ntex5 ratio (isoform with an out of frame skip of the last 22 nucleotides of exon 5) and a twofold increase of the BRCA1-Deltaex5 ratio. These altered ratios are most likely to result from increased expression of the alternative transcripts, although we cannot completely rule out a small decrease of the total BRCA1 expression level due to highly variable BRCA1 levels in cultured cell lines. In order to explore the functional significance of the isoforms, we evaluated their prevalence in normal tissues and cancer cell lines. The BRCA1-Delta22ntex5 ratio was significantly higher in an ovarian cancer cell line compared to normal ovarian tissue. Our findings suggest that revealing the defects caused by some splice mutations requires accurate quantitative methods. We hypothesize that disruption of alternative transcript ratios of BRCA1 may be a dominant mechanism affecting predisposition to hereditary breast and/or ovarian cancer.
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