ArticleNature communications2019
BRCA1 intronic Alu elements drive gene rearrangements and PARP inhibitor resistance.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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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
41 citing papers in PubMed, 60 citations in OpenAlex.
- Copy number variants in BRCA1 and BRCA2 genes in Polish patients with breast and ovarian cancer.Journal of cancer research and clinical oncology · 2026Article
- Review
- Article
- The role of Alu elements in causing BRCA1 structural variation and breast cancer susceptibility.Genes & genomics · 2026Review
- Review
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- Retroelement co-option disrupts the cancer transcriptional programme.Genome medicine · 2025Article
- Germline Testing in Breast Cancer: A Single-Center Analysis Comparing Strengths and Challenges of Different Approaches.Cancers · 2025Article
- Multi-ancestry GWAS reveals loci linked to human variation in LINE-1- and Alu-insertion numbers.bioRxiv : the preprint server for biology · 2025Article
- Multi-ancestry GWAS reveals loci linked to human variation in LINE-1- and Alu-insertion numbers.Translational medicine of aging · 2025Article
- Portable microfluidic devices for monitoring antibiotic resistance genes in wastewater.Mikrochimica acta · 2024Review
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- Unveiling the relationship between WWOX and BRCA1 in mammary tumorigenicity and in DNA repair pathway selection.Cell death discovery · 2024Article
- Protein-folding chaperones predict structure-function relationships and cancer risk in BRCA1 mutation carriers.Cell reports · 2024Article
- Identifying Relationships betweenAnimals : an open access journal from MDPI · 2024Article
- Circulating Tumor DNA Enables Sensitive Detection of Actionable Gene Fusions and Rearrangements Across Cancer Types.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Small-scale mutations are infrequent as mechanisms of resistance in post-PARP inhibitor tumour samples in high grade serous ovarian cancer.Scientific reports · 2023Article
- Genetic separation of Brca1 functions reveal mutation-dependent Polθ vulnerabilities.Nature communications · 2023Article
- BRACNAC: AInternational journal of molecular sciences · 2023Article
- CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer.Nature communications · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
BRCA1 mutant carcinomas are sensitive to PARP inhibitor (PARPi) therapy; however, resistance arises. BRCA1 BRCT domain mutant proteins do not fold correctly and are subject to proteasomal degradation, resulting in PARPi sensitivity. In this study, we show that cell lines and patient-derived tumors, with highly disruptive BRCT domain mutations, have readily detectable BRCA1 protein expression, and are able to proliferate in the presence of PARPi. Peptide analyses reveal that chemo-resistant cancers contain residues encoded by BRCA1 intron 15. Mechanistically, cancers with BRCT domain mutations harbor BRCA1 gene breakpoints within or adjacent to Alu elements in intron 15; producing partial gene duplications, inversions and translocations, and terminating transcription prior to the mutation-containing BRCT domain. BRCA1 BRCT domain-deficient protein isoforms avoid mutation-induced proteasomal degradation, support homology-dependent DNA repair, and promote PARPi resistance. Taken together, Alu-mediated BRCA1 gene rearrangements are responsible for generating hypomorphic proteins, and may represent a biomarker of PARPi resistance.
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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.