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ResearchIn-Press PreviewCell biologyGastroenterology
Open Access | 
10.1172/JCI191855
Somatic mutations in TBX3 promote hepatic clonal expansion by accelerating VLDL secretion
Gregory Mannino,1 Gabriella Quinn,2 Min Zhu,1 Zixi Wang,1 Xun Wang,1 Boyuan Li,1 Meng-Hsiung Hsieh,1 Thomas Mathews,1 Lauren Zacharias,1 Wen Gu,1 Purva Gopal,3 Natalia Brzozowska,4 Peter Campbell,4 Matt Hoare,5 Glen Liszczak,6 and Hao Zhu1
1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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Wang, Z.
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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Wang, X.
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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Hoare, M.
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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1Children’s Research Institute, Department of Pediatrics and Internal Medici, Simmons Comprehensive Cancer Center, Children’s Research Institute Mouse Genome Engineering Core, University of Texas Southwestern Medical Center, Dallas, United States of America
2Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States of America
3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, United States of America
4Cancer Genome Project, Wellcome Sanger Institute, Hinxton, United Kingdom
5Department of Medicine, University of Cambridge Early Cancer Institute, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States of America
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Zhu, H.
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Published July 10, 2025 - More info
Copyright © 2025, Mannino et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)