ArticleCancer research2014
TALEN-mediated somatic mutagenesis in murine models of cancer.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Advanced gene editing technologies for oncology mechanisms, applications, and clinical implementation.Cancer gene therapy · 2026Review
- Lipid nanoparticle delivery of TALEN mRNA targeting LPA causes gene disruption and plasma lipoprotein(a) reduction in transgenic mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The origins and functions of hepatic polyploidy.Cell cycle (Georgetown, Tex.) · 2019Review
- Targeting LIN28B reprograms tumor glucose metabolism and acidic microenvironment to suppress cancer stemness and metastasis.Oncogene · 2019Article
- The Polyploid State Restricts Hepatocyte Proliferation and Liver Regeneration in Mice.Hepatology (Baltimore, Md.) · 2019Article
- Applications of Genome Editing Technology in Animal Disease Modeling and Gene Therapy.Computational and structural biotechnology journal · 2019Review
- The Polyploid State Plays a Tumor-Suppressive Role in the Liver.Developmental cell · 2018Article
- CRISPR/Cas9 Genome Editing of Epidermal Growth Factor Receptor Sufficiently Abolished Oncogenicity in Anaplastic Thyroid Cancer.Disease markers · 2018Article
- Alcohol and Cancer: Mechanisms and Therapies.Biomolecules · 2017Review
- Article
- Gene editing for corneal disease management.World journal of translational medicine · 2016Article
- Engineered Viruses as Genome Editing Devices.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
- The search for precision models clinically relevant to human liver cancer.Hepatic oncology · 2015Article
- A versatile reporter system for CRISPR-mediated chromosomal rearrangements.Genome biology · 2015Article
- TALEN-mediated genome engineering to generate targeted mice.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2015Review
- Precision cancer mouse models through genome editing with CRISPR-Cas9.Genome medicine · 2015Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cancer genome sequencing has identified numerous somatic mutations whose biologic relevance is uncertain. In this study, we used genome-editing tools to create and analyze targeted somatic mutations in murine models of liver cancer. Transcription activator-like effector nucleases (TALEN) were designed against β-catenin (Ctnnb1) and adenomatous polyposis coli (Apc), two commonly mutated genes in hepatocellular carcinoma (HCC), to generate isogenic HCC cell lines. Both mutant cell lines exhibited evidence of Wnt pathway dysregulation. We asked whether these TALENs could create targeted somatic mutations after hydrodynamic transfection into mouse liver. TALENs targeting β-catenin promoted endogenous HCC carrying the intended gain-of-function mutations. However, TALENs targeting Apc were not as efficient in inducing in vivo homozygous loss-of-function mutations. We hypothesized that hepatocyte polyploidy might be protective against TALEN-induced loss of heterozygosity, and indeed Apc gene editing was less efficient in tetraploid than in diploid hepatocytes. To increase efficiency, we administered adenoviral Apc TALENs and found that we could achieve a higher mutagenesis rate in vivo. Our results demonstrate that genome-editing tools can enable the in vivo study of cancer genes and faithfully recapitulate the mosaic nature of mutagenesis in mouse cancer models. Cancer Res; 74(18); 5311-21. ©2014 AACR.
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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.