ArticleCancer research2016
The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.
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.
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.
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Who cites it
182 citing papers in PubMed, 1 synthesis or guideline pooled it, 267 citations in OpenAlex.
- BRCA1 Expression by Immunohistochemistry and Prognosis in Ovarian Cancer: A Systematic Review and Meta-Analysis.Targeted oncology · 2020Pooled 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
- Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Secondary Somatic Mutations RestoringCancer discovery · 2017Trial
- DNA end-resection is stimulated by an interaction between BRCA1 exon 11 and TOPBP1.EMBO reports · 2026Article
- PUM3 is an essential suppressor of replication stress in homologous recombination deficient breast cancer.Nature communications · 2026Article
- TheBiomolecular NMR assignments · 2026Article
- Alternative Splicing in Cyclin-Dependent Kinase 4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer.Drug development research · 2026Review
- g BRCA1 and g BRCA2 mutations in specific different domains affect ovarian cancer prognosis: A multicenter retrospective study.Chinese medical journal · 2026Article
- Alternative splicing rewires breast cancer and opens therapeutic avenues.Cell communication and signaling : CCS · 2026Review
- Review
- Clinicopathologic and molecular predictors of survival in BRCA-deficient tubo-ovarian high-grade serous carcinoma.Nature communications · 2026Article
- Improving isoform-level eQTL and integrative genetic analyses of breast cancer risk with long-read RNA transcript assemblies.bioRxiv : the preprint server for biology · 2026Article
- Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- The role of Alu elements in causing BRCA1 structural variation and breast cancer susceptibility.Genes & genomics · 2026Review
- Overcoming Resistance to PARP Inhibitors in BRCA-Mutated Cancers: Mechanisms and Therapeutic Strategies.Journal of Cancer · 2026Review
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- Alternative splicing: from tumorigenesis to neoantigen-mediated cancer immunotherapy.Biomarker research · 2025Review
- Genetic evidence for PARP1 trapping as a driver of PARP inhibitor efficacy in BRCA mutant cancer cells.Nucleic acids research · 2025Article
122 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
39 authors at 20 institutions in 11 countries.
Funding
Abstract
Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and therapeutic response. Cancer cell lines and tumors harboring mutations in exon 11 of BRCA1 express a BRCA1-Δ11q splice variant lacking the majority of exon 11. The introduction of frameshift mutations to exon 11 resulted in nonsense-mediated mRNA decay of full-length, but not the BRCA1-Δ11q isoform. CRISPR/Cas9 gene editing as well as overexpression experiments revealed that the BRCA1-Δ11q protein was capable of promoting partial PARPi and cisplatin resistance relative to full-length BRCA1, both in vitro and in vivo Furthermore, spliceosome inhibitors reduced BRCA1-Δ11q levels and sensitized cells carrying exon 11 mutations to PARPi treatment. Taken together, our results provided evidence that cancer cells employ a strategy to remove deleterious germline BRCA1 mutations through alternative mRNA splicing, giving rise to isoforms that retain residual activity and contribute to therapeutic resistance. Cancer Res; 76(9); 2778-90. ©2016 AACR.
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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.