ArticleNature genetics2010
Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements.
Article in Nature genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 358 papers.
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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
358 citing papers in PubMed, 607 citations in OpenAlex.
- Bipolar androgen therapy plus nivolumab for patients with metastatic castration-resistant prostate cancer: the COMBAT phase II trial.Nature communications · 2024Trial
- A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts.European urology · 2021Trial
- Bipolar androgen therapy sensitizes castration-resistant prostate cancer to subsequent androgen receptor ablative therapy.European journal of cancer (Oxford, England : 1990) · 2021Trial
- Targeting Androgen Receptor and DNA Repair in Metastatic Castration-Resistant Prostate Cancer: Results From NCI 9012.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Bipolar androgen therapy in men with metastatic castration-resistant prostate cancer after progression on enzalutamide: an open-label, phase 2, multicohort study.The Lancet. Oncology · 2018Trial
- Circulating Antioxidant Levels and Risk of Prostate Cancer by TMPRSS2:ERG.The Prostate · 2017Trial
- Beyond androgen deprivation therapy: Next-generation hormonal therapies and emerging combination approaches in advanced prostate cancer.Urologic oncology · 2026Review
- Bipolar Androgen Therapy as a Potential Mechanistic Bridge to Enhance PARP Inhibitor Efficacy in Prostate Cancer.The Kaohsiung journal of medical sciences · 2026Article
- Androgens mediate sexual dimorphism in Pilarowski-Bjornsson syndrome.American journal of human genetics · 2026Article
- A Spatiotemporal Atlas of the Androgen Receptor Proximal Interactome.bioRxiv : the preprint server for biology · 2026Article
- DNA topological regulation by topoisomerase IIβ-DNA-PK interaction is important for controlled hypoxia-inducible gene expression.bioRxiv : the preprint server for biology · 2026Article
- PDS5A and TOP2B cooperate for chromatin recruitment via CTCF.bioRxiv : the preprint server for biology · 2026Article
- TMPRSS2:ERG-directed radiosensitization: exploiting DNA repair rewiring in gene fusion-positive prostate cancer.The Journal of clinical investigation · 2026Article
- DNA topological regulation in RNA polymerase II transcription.Cellular & molecular biology letters · 2026Review
- Exploring the biology of metastatic hormone-sensitive prostate cancer: on the road to precision medicine.The Journal of clinical investigation · 2026Review
- Esketamine/Ketamine: Dual-Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- ESR1 fusions in breast cancer: functions, mechanisms and therapeutic opportunities.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Review
- TOP2B modulates DNA supercoiling and chromatin contacts during transcriptional induction.Science advances · 2025Article
- Topoisomerase IIb binding delineates localized mutational processes and driver mutations in cancer genomes.Nature communications · 2025Article
- The interconnection between androgen receptor and DNA damage response pathways in prostate cancer.Current urology · 2025Review
298 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
DNA double-strand breaks (DSBs) can lead to the development of genomic rearrangements, which are hallmarks of cancer. Fusions between TMPRSS2, encoding the transmembrane serine protease isoform 2, and ERG, encoding the v-ets erythroblastosis virus E26 oncogene homolog, are among the most common oncogenic rearrangements observed in human cancer. We show that androgen signaling promotes co-recruitment of androgen receptor and topoisomerase II beta (TOP2B) to sites of TMPRSS2-ERG genomic breakpoints, triggering recombinogenic TOP2B-mediated DSBs. Furthermore, androgen stimulation resulted in de novo production of TMPRSS2-ERG fusion transcripts in a process that required TOP2B and components of the DSB repair machinery. Finally, unlike normal prostate epithelium, prostatic intraepithelial neoplasia cells showed strong coexpression of androgen receptor and TOP2B. These findings implicate androgen-induced TOP2B-mediated DSBs in generating TMPRSS2-ERG rearrangements.
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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.