ArticleThe Journal of clinical investigation2009
Expression of human BRCA1 variants in mouse ES cells allows functional analysis of BRCA1 mutations.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 67 citations in OpenAlex.
- Functional assays for BRCA1 and BRCA2 variant analysis: new tools and their applications.NPJ breast cancer · 2026Review
- Thirty Years of BRCA1: Mechanistic Insights and Their Impact on Mutation Carriers.Cancer discovery · 2025Review
- BRCA1 the Versatile Defender: Molecular to Environmental Perspectives.International journal of molecular sciences · 2023Review
- Article
- The p.Ser64Leu and p.Pro104Leu missense variants of PALB2 identified in familial pancreatic cancer patients compromise the DNA damage response.Human mutation · 2021Article
- A computational model for classification of BRCA2 variants using mouse embryonic stem cell-based functional assays.NPJ genomic medicine · 2020Article
- Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers.Journal of experimental & clinical cancer research : CR · 2020Review
- Functional Characterization ofFrontiers in molecular biosciences · 2020Review
- Functional analysis of genetic variants in the high-risk breast cancer susceptibility gene PALB2.Nature communications · 2019Article
- Genetic Testing to Guide Risk-Stratified Screens for Breast Cancer.Journal of personalized medicine · 2019Review
- A new bioinformatics tool to help assess the significance of BRCA1 variants.Human genomics · 2018Article
- microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer.Oncogene · 2018Article
- Homology-Directed Repair and the Role of BRCA1, BRCA2, and Related Proteins in Genome Integrity and Cancer.Annual review of cancer biology · 2018Article
- BRE/BRCC45 regulates CDC25A stability by recruiting USP7 in response to DNA damage.Nature communications · 2018Article
- A Novel Germline Mutation inJournal of breast cancer · 2017Article
- Functional and mutational landscapes of BRCA1 for homology-directed repair and therapy resistance.eLife · 2017Article
- Hereditary breast and ovarian cancer: new genes in confined pathways.Nature reviews. Cancer · 2016Review
- Article
- Simultaneous inhibition of multiple oncogenic miRNAs by a multi-potent microRNA sponge.Oncotarget · 2015Article
- Homologous recombination and human health: the roles of BRCA1, BRCA2, and associated proteins.Cold Spring Harbor perspectives in biology · 2015Review
Corrections and comments
- Commented on by
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
To date, inheritance of a mutant BRCA1 or BRCA2 gene is the best-established indicator of an increased risk of developing breast cancer. Sequence analysis of these genes is being used to identify BRCA1/2 mutation carriers, though these efforts are hampered by the high frequency of variants of unknown clinical significance (VUSs). Functional evaluation of such variants has been restricted due to lack of a physiologically relevant assay. In this study we developed a functional assay using mouse ES cells to study variants of BRCA1. We introduced BAC clones with human wild-type BRCA1 or variants into Brca1-null ES cells and confirmed that only wild-type and a known neutral variant rescued cell lethality. The same neutral variant was also able to rescue embryogenesis in Brca1-null mice. A test of several BRCT domain mutants revealed all to be deleterious, including a VUS. Furthermore, we used this assay to determine the effects of BRCA1 variants on cell cycle regulation, differentiation, and genomic stability. Importantly, we discovered that ES cells rescued by S1497A BRCA1 exhibited significant hypersensitivity after gamma-irradiation. Our results demonstrate that this ES cell-based assay is a powerful and reliable method for analyzing the functional impact of BRCA1 variants, which we believe could be used to determine which patients may require preventative treatments.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.