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*
(all 24)
PubMed
30192230 Full text @ Elife
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
Marker Marker Type Name
mitfaGENEmelanocyte inducing transcription factor a
mpv17GENEmitochondrial inner membrane protein MPV17
tp53GENEtumor protein p53
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Figures
Figure Gallery (4 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WTgamma rayPrim-15
tp53fb105/fb105standard conditionsPrim-5
tp53fb105/fb105standard conditionsAdult
tp53fb105/fb105standard conditionsAdult
tp53fb105/fb105standard conditionsAdult
tp53fb105/fb105standard conditionsAdult
tp53fb105/fb105standard conditionsAdult
tp53fb105/fb105standard conditionsAdult
tp53fb105/fb105gamma rayPrim-15
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
a9
    		Complex
    cz1703TgTransgenic Insertion
      fb105
        		Indel
        w2
          		Point Mutation
          zdf8TgTransgenic Insertion
            zf49TgTransgenic Insertion
              1 - 6 of 6
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              Human Disease / Model
              Human Disease Fish Conditions Evidence
              aggressive NK-cell leukemiatp53fb105/fb105standard conditionsTAS
              angiosarcomatp53fb105/fb105standard conditionsTAS
              cancertp53fb105/fb105standard conditionsTAS
              Li-Fraumeni syndromeTAS
              rhabdomyosarcomaTAS
              1 - 5 of 5
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              Sequence Targeting Reagents
              Target Reagent Reagent Type
              tp53TALEN2-tp53TALEN
              tp53TALEN3-tp53TALEN
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              Fish
              Fish
              tp53fb105/fb105
              WT
              1 - 2 of 2
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              Antibodies
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              DsRed2EFGDsRed2
              EGFPEFGEGFP
              GFPEFGGFP
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              Mapping
              No data available
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              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:.