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 tp53 del/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.
journal_name
Elifejournal_title
eLifeauthors
Ignatius MS,Hayes MN,Moore FE,Tang Q,Garcia SP,Blackburn PR,Baxi K,Wang L,Jin A,Ramakrishnan A,Reeder S,Chen Y,Nielsen GP,Chen EY,Hasserjian RP,Tirode F,Ekker SC,Langenau DMdoi
10.7554/eLife.37202subject
Has Abstractpub_date
2018-09-07 00:00:00issn
2050-084Xpii
37202journal_volume
7pub_type
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