ArticleThe Journal of clinical investigation2016
BRCA1185delAG tumors may acquire therapy resistance through expression of RING-less BRCA1.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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
91 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Assessing the benefits and safety profile of incorporating poly ADP-ribose polymerase (PARP) inhibitors in the treatment of advanced lung cancer: a thorough systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2).Nature communications · 2021Trial
- Germline homologous recombination deficiency influences TP53-mutant clonal hematopoiesis fitness during platinum and PARP inhibitor treatment.Nature genetics · 2026Article
- Insights from three decades of BRCA1/2 modeling in mice.Nature genetics · 2026Review
- 53BP1-independent Shieldin-BRCA1 antagonism at replication-coupled double-strand breaks.Nature communications · 2026Article
- g BRCA1 and g BRCA2 mutations in specific different domains affect ovarian cancer prognosis: A multicenter retrospective study.Chinese medical journal · 2026Article
- Nucleophagy removes cytotoxic trapped PARP1.Nature cell biology · 2026Article
- Review
- Article
- Triple-Action Therapy: Combining Machine Learning, Docking, and Dynamics to Combat BRCA1-Mutated Breast Cancer.Molecular biotechnology · 2025Article
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- Thirty Years of BRCA1: Mechanistic Insights and Their Impact on Mutation Carriers.Cancer discovery · 2025Review
- Examining patient-specific responses to PARP inhibitors in a novel, human induced pluripotent stem cell-based model of breast cancer.NPJ precision oncology · 2025Article
- BRCA1 and BRCA2: from cancer susceptibility to synthetic lethality.Genes & development · 2025Review
- Evaluation of the Oncomine Comprehensive Assay Plus NGS Panel and the OncoScan CNV Assay for Homologous Recombination Deficiency Detection.Molecular diagnosis & therapy · 2025Article
- BRCA1 & BRCA2 methylation as a prognostic and predictive biomarker in cancer: Implementation in liquid biopsy in the era of precision medicine.Clinical epigenetics · 2024Review
- Brca1 haploinsufficiency promotes early tumor onset and epigenetic alterations in a mouse model of hereditary breast cancer.Nature genetics · 2024Article
- FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.EMBO molecular medicine · 2024Article
- Article
- Efficacy of PARP inhibitors in advanced high-grade serous ovarian cancer according to BRCA domain mutations and mutation type.Frontiers in oncology · 2024Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
29 authors.
Funding
Abstract
Heterozygous germline mutations in breast cancer 1 (BRCA1) strongly predispose women to breast cancer. BRCA1 plays an important role in DNA double-strand break (DSB) repair via homologous recombination (HR), which is important for tumor suppression. Although BRCA1-deficient cells are highly sensitive to treatment with DSB-inducing agents through their HR deficiency (HRD), BRCA1-associated tumors display heterogeneous responses to platinum drugs and poly(ADP-ribose) polymerase (PARP) inhibitors in clinical trials. It is unclear whether all pathogenic BRCA1 mutations have similar effects on the response to therapy. Here, we have investigated mammary tumorigenesis and therapy sensitivity in mice carrying the Brca1185stop and Brca15382stop alleles, which respectively mimic the 2 most common BRCA1 founder mutations, BRCA1185delAG and BRCA15382insC. Both the Brca1185stop and Brca15382stop mutations predisposed animals to mammary tumors, but Brca1185stop tumors responded markedly worse to HRD-targeted therapy than did Brca15382stop tumors. Mice expressing Brca1185stop mutations also developed therapy resistance more rapidly than did mice expressing Brca15382stop. We determined that both murine Brca1185stop tumors and human BRCA1185delAG breast cancer cells expressed a really interesting new gene domain-less (RING-less) BRCA1 protein that mediated resistance to HRD-targeted therapies. Together, these results suggest that expression of RING-less BRCA1 may serve as a marker to predict poor response to DSB-inducing therapy in human cancer patients.
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.