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Elife. 2018 Sep 7;7. pii: e37202. doi: 10.7554/eLife.37202.

tp53 deficiency causes a wide tumor spectrum and increases embryonal rhabdomyosarcoma metastasis in zebrafish.

Author information

Department of Pathology, Massachusetts General Hospital Research Institute, Boston, Massachusetts.
Center of Cancer Research, Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts.
Harvard Stem Cell Institute, Boston, Massachusetts.
Department of Molecular Medicine, Greehey Children's Cancer Research Institute, San Antonio, Texas.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, United States.
Department of Pathology, University of Washington, Seattle, United States.
Department of Translational Research and Innovation, Université Claude Bernard Lyon, Cancer Research Center of Lyon, Lyon, France.
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United States.
Contributed equally


The TP53 tumor-suppressor gene is mutated in >50% of human tumors and Li-Fraumeni patients with germ line inactivation are predisposed to developing cancer. Here, we generated tp53 deleted zebrafish that spontaneously develop malignant peripheral nerve-sheath tumors, angiosarcomas, germ cell tumors, and an aggressive Natural Killer cell-like leukemia for which no animal model has been developed. Because the tp53 deletion was generated in syngeneic zebrafish, engraftment of fluorescent-labeled tumors could be dynamically visualized over time. Importantly, engrafted tumors shared gene expression signatures with predicted cells of origin in human tissue. Finally, we showed that tp53del/del enhanced invasion and metastasis in kRASG12D-induced embryonal rhabdomyosarcoma (ERMS), but did not alter the overall frequency of cancer stem cells, suggesting novel pro-metastatic roles for TP53 loss-of-function in human muscle tumors. In summary, we have developed a Li-Fraumeni zebrafish model that is amenable to large-scale transplantation and direct visualization of tumor growth in live animals.


MPNST; angiosarcoma; cancer biology; germ cell tumor; leukemia; metastasis; rhabdomyosarcoma; zebrafish

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