ArticleCancer research2010
Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
What it found
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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.
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Who cites it
103 citing papers in PubMed, 164 citations in OpenAlex.
- g BRCA1 and g BRCA2 mutations in specific different domains affect ovarian cancer prognosis: A multicenter retrospective study.Chinese medical journal · 2026Article
- Domain-Specific Computational, Functional and Structural Methods Enable Interpretation ofCurrent oncology (Toronto, Ont.) · 2026Article
- BARD1 recognizes pre-rRNA for DNA damage repair and rRNA biogenesis.The Journal of biological chemistry · 2026Article
- Genetic background shapes AI-predicted variant effects.bioRxiv : the preprint server for biology · 2026Article
- HSP90 buffers deleterious genetic variations in BRCA1.Molecular cell · 2025Article
- Functional characterization of BRCA1 variants of unknown significance using homologous recombination repair assays.Breast cancer research : BCR · 2025Article
- Hidden SVA retrotransposon insertion in BRCA1 revealed by nanopore targeted sequencing causes hereditary breast and ovarian cancer.Journal of human genetics · 2025Article
- Profiling BRCA1-BRCT interactions and their functional relevance at amino acid resolution.Nucleic acids research · 2025Article
- Thirty Years of BRCA1: Mechanistic Insights and Their Impact on Mutation Carriers.Cancer discovery · 2025Review
- Reduced penetrance BRCA1 and BRCA2 pathogenic variants in clinical germline genetic testing.NPJ precision oncology · 2024Article
- Reversion of pathogeniciScience · 2024Article
- BRCA1 and Its Vulnerable C-Terminal BRCT Domain: Structure, Function, Genetic Mutations and Links to Diagnosis and Treatment of Breast and Ovarian Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Protein-folding chaperones predict structure-function relationships and cancer risk in BRCA1 mutation carriers.Cell reports · 2024Article
- BRCA1, BRCA2, and TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer.Cancer medicine · 2024Article
- MoDAFold: a strategy for predicting the structure of missense mutant protein based on AlphaFold2 and molecular dynamics.Briefings in bioinformatics · 2024Article
- BRCA1 and BRCA2 germline mutations in Chinese Hakka breast cancer patients.BMC medical genomics · 2024Article
- Clinical case study meets population cohort: identification of a BRCA1 pathogenic founder variant in Orcadians.European journal of human genetics : EJHG · 2023Article
- Functional analyses of rare germline BRCA1 variants by transcriptional activation and homologous recombination repair assays.BMC cancer · 2023Article
- Article
- BRCA Mutations-The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers.International journal of molecular sciences · 2023Review
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Genetic screening of the breast and ovarian cancer susceptibility gene BRCA1 has uncovered a large number of variants of uncertain clinical significance. Here, we use biochemical and cell-based transcriptional assays to assess the structural and functional defects associated with a large set of 117 distinct BRCA1 missense variants within the essential BRCT domain of the BRCA1 protein that have been documented in individuals with a family history of breast or ovarian cancer. In the first method, we used limited proteolysis to assess the protein folding stability of each of the mutants compared with the wild-type. In the second method, we used a phosphopeptide pull-down assay to assess the ability of each of the variants to specifically interact with a peptide containing a pSer-X-X-Phe motif, a known functional target of the BRCA1 BRCT domain. Finally, we used transcriptional assays to assess the ability of each BRCT variant to act as a transcriptional activation domain in human cells. Through a correlation of the assay results with available family history and clinical data, we define limits to predict the disease risk associated with each variant. Forty-two of the variants show little effect on function and are likely to represent variants with little or no clinical significance; 50 display a clear functional effect and are likely to represent pathogenic variants; and the remaining 25 variants display intermediate activities. The excellent agreement between the structure/function effects of these mutations and available clinical data supports the notion that functional and structure information can be useful in the development of models to assess cancer risk.
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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.