ArticleProceedings of the National Academy of Sciences of the United States of America2009
Chromosomal translocations induced at specified loci in human stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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Who cites it
121 citing papers in PubMed, 202 citations in OpenAlex.
- Emerging insights into alternative end‑joining: Mechanisms, genome instability and therapeutic opportunities in cancer (Review).International journal of oncology · 2025Review
- Applications of multiplexed CRISPR-Cas for genome engineering.Experimental & molecular medicine · 2025Review
- Assessment and Mitigation of CRISPR-Cas9-Induced Nontargeted Translocations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Enhancing tiny millets through genome editing: current status and future prospects.Molecular genetics and genomics : MGG · 2025Review
- CRISPR-Cas9-mediated genome editing delivered by a single AAV9 vector inhibits HSV-1 reactivation in a latent rabbit keratitis model.Molecular therapy. Methods & clinical development · 2024Article
- A mechanistic study on the tolerance of PAM distal end mismatch by SpCas9.The Journal of biological chemistry · 2024Article
- Modeling Extraordinary Response Through Targeting Secondary Alterations in Fusion-Associated Sarcoma.JCO precision oncology · 2024Article
- Microhomology-mediated repair machinery and its relationship with HPV-mediated oncogenesis.Journal of medical virology · 2024Review
- Specificity of cancer-related chromosomal translocations is linked to proximity after the DNA double-strand break and subsequent selection.NAR cancer · 2023Article
- Modeling sarcoma relevant translocations using CRISPR-Cas9 in human embryonic stem derived mesenchymal precursors.Genes, chromosomes & cancer · 2023Review
- A functional sgRNA-CRISPR screening method for generating murine RET and NTRK1 rearranged oncogenes.Biology open · 2023Article
- Minimizing the off-target frequency of the CRISPR/Cas9 systemChemical science · 2023Article
- Precision Editing as a Therapeutic Approach for β-Hemoglobinopathies.International journal of molecular sciences · 2023Review
- A Rapid, Functional sgRNA Screening Method for Generating Murine RET and NTRK1 Fusion Oncogenes.bioRxiv : the preprint server for biology · 2023Article
- Targeted genomic translocations and inversions generated using a paired prime editing strategy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Review
- Daisy-chain gene drives: The role of low cut-rate, resistance mutations, and maternal deposition.PLoS genetics · 2022Article
- Speciation and adaptation research meets genome editing.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- Editing outside the body: Ex vivo gene-modification for β-hemoglobinopathy cellular therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Unraveling Ewing Sarcoma Tumorigenesis Originating from Patient-Derived Mesenchymal Stem Cells.Cancer research · 2021Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
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Abstract
The precise genetic manipulation of stem and precursor cells offers extraordinary potential for the analysis, prevention, and treatment of human malignancies. Chromosomal translocations are hallmarks of several tumor types where they are thought to have arisen in stem or precursor cells. Although approaches exist to study factors involved in translocation formation in mouse cells, approaches in human cells have been lacking, especially in relevant cell types. The technology of zinc finger nucleases (ZFNs) allows DNA double-strand breaks (DSBs) to be introduced into specified chromosomal loci. We harnessed this technology to induce chromosomal translocations in human cells by generating concurrent DSBs at 2 endogenous loci, the PPP1R12C/p84 gene on chromosome 19 and the IL2Rgamma gene on the X chromosome. Translocation breakpoint junctions for t(19;X) were detected with nested quantitative PCR in a high throughput 96-well format using denaturation curves and DNA sequencing in a variety of human cell types, including embryonic stem (hES) cells and hES cell-derived mesenchymal precursor cells. Although readily detected, translocations were less frequent than repair of a single DSB by gene targeting or nonhomologous end-joining, neither of which leads to gross chromosomal rearrangements. While previous studies have relied on laborious genetic modification of cells and extensive growth in culture, the approach described in this report is readily applicable to primary human cells, including multipotent and pluripotent cells, to uncover both the underlying mechanisms and phenotypic consequences of targeted translocations and other genomic rearrangements.
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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.