PUBLICATION
tp53 deficiency causes a wide tumor spectrum and increases embryonal rhabdomyosarcoma metastasis in zebrafish.
- Authors
- Ignatius, M.S., Hayes, M.N., Moore, F.E., Tang, Q., Garcia, S.P., Blackburn, P.R., Baxi, K., Wang, L., Jin, A., Ramakrishnan, A., Reeder, S., Chen, Y., Nielsen, G.P., Chen, E.Y., Hasserjian, R.P., Tirode, F., Ekker, S.C., Langenau, D.M.
- ID
- ZDB-PUB-180908-8
- Date
- 2018
- Source
- eLIFE 7: (Journal)
- Registered Authors
- Blackburn, Patrick, Ekker, Stephen C., Hayes, Madeline, Ignatius, Myron, Langenau, David, Tang, Qin
- Keywords
- MPNST, angiosarcoma, cancer biology, germ cell tumor, leukemia, metastasis, rhabdomyosarcoma, zebrafish
- Datasets
- GEO:GSE109581
- MeSH Terms
-
- Animals
- Cell Count
- Gene Deletion
- Gene Expression Regulation, Neoplastic
- Hemangiosarcoma/metabolism
- Hemangiosarcoma/pathology
- Homozygote
- Leukemia/metabolism
- Leukemia/pathology
- Neoplasm Invasiveness
- Neoplasm Metastasis
- Neoplasm Transplantation
- Neoplasms, Germ Cell and Embryonal/metabolism
- Neoplasms, Germ Cell and Embryonal/pathology
- Neoplastic Stem Cells/metabolism
- Neoplastic Stem Cells/pathology
- Rhabdomyosarcoma, Embryonal/genetics
- Rhabdomyosarcoma, Embryonal/metabolism*
- Rhabdomyosarcoma, Embryonal/pathology*
- Survival Analysis
- Tumor Suppressor Protein p53/deficiency*
- Tumor Suppressor Protein p53/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism*
- PubMed
- 30192230 Full text @ Elife
Citation
Ignatius, M.S., Hayes, M.N., Moore, F.E., Tang, Q., Garcia, S.P., Blackburn, P.R., Baxi, K., Wang, L., Jin, A., Ramakrishnan, A., Reeder, S., Chen, Y., Nielsen, G.P., Chen, E.Y., Hasserjian, R.P., Tirode, F., Ekker, S.C., Langenau, D.M. (2018) tp53 deficiency causes a wide tumor spectrum and increases embryonal rhabdomyosarcoma metastasis in zebrafish.. eLIFE. 7:.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping