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

We generated tp53 deletion mutant zebrafish that spontaneously develop malignant peripheral nerve-sheath tumors, angiosarcomas, germ cell tumors, and an aggressive Natural Killer cell leukemia not previously reported in zebrafish. Each tumor type efficiently engrafted into syngeneic recipient zebrafish and shared gene expression signatures with predicted cells of origin. We generated a complete-null tp53 deletion allele in syngeneic CG1 strain zebrafish using TALEN endonucleases. The list of tumors spontaneously developed in these tp53del/del animals included malignant peripheral nerve-sheath tumors (MPNSTs), angiosarcomas, germ cell tumors, and Natural Killer cell leukemia. We obtained 3 MPNSTs samples (MPNST_1, MPNST_2 and MPNST_3), 2 angiosarcoma samples (Angiosarcoma_1 and Angiosarcoma_2), 3 leukemia samples (Leukemia_1, Leukemia_2 and Leukemia_3), and 1 sample of germ cell tumor (GermCell_1). We also assessed the role of tp53 in kRASG12D-induced human embryonal rhabdomyosarcoma (ERMS) using large-scale cell transplantation assays and live fluorescent imaging over time. We obtained 3 ERMS samples (ERMS_1, ERMS_2 and ERMS_3). All these tumor samples were compared to 3 background CG1 samples (samples WholeFish_1, WholeFish_2 and WholeFish_3).