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Tp53 deficiency causes a wide tumor spectrum and elevates embryonal rhabdomyosarcoma metastasis in zebrafish

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

PROVIDER: PRJNA431425 | ENA |

REPOSITORIES: ENA

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

Project description: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.

2018-09-05 | GSE109581 | GEO

Defining function of wild-type and three patient specific TP53 mutations in a zebrafish model of embryonal rhabdomyosarcoma

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Mouse Models of Alveolar/Embryonal Rhabdomyosarcoma & Spindle Cell Sarcomas

Project description:A series of conditional mouse models of embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma and spindle cell sarcoma were generated and validated for relavence to corresponding human cancers. Conditional mouse models of embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma and spindle cell sarcoma were created by activation or deletion of Pax3:Fkhr, p53, Ptch1 or Rb1 genes.

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

Project description: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.

| S-EPMC6128690 | biostudies-literature

SNP array data for embryonal rhabdomyosarcoma in a patient with Costello syndrome

Project description:Affymetrix SNP array data for embryonal rhabdomyosarcoma in a patient with Costello syndrome

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Expression profile of zebrafish embryonal rhabdomyosarcoma

Project description:Fluorescent-labeled zebrafish RAS-induced embryonal rhabdomyosarcoma (ERMS) were created to facilitate in vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in diverse cellular compartments. Using this strategy, we have identified a molecularly distinct ERMS cell subpopulation that expresses high levels of myf5 and is enriched for ERMS-propagating potential when compared with other tumor-derived cells. Embryonal rhabdomyosarcoma (ERMS) is an aggressive pediatric sarcoma of muscle. Here, we show that tumor-propagating potential is confined to myf5+ERMS cells and can be visualized in live, fluorescent transgenic zebrafish. During early tumor growth, myf5+ERMS cells reside within an expanded satellite cell compartment, but by late stage ERMS, myf5+cells are dynamically reorganized into distinct regions separated from differentiated tumor cells. Human ERMS also contain distinct areas of differentiated and undifferentiated cells. Time-lapse imaging revealed that myf5+ERMS cells populate newly formed tumor only after seeding by highly migratory myogenin+ ERMS cells. This finding helps explain the clinical observation that Myogenin positivity correlates with poor clinical outcome in human ERMS and suggests that differentiated tumor cells play critical roles in metastasis.

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SNP array data for embryonal rhabdomyosarcoma in a patient with Costello syndrome

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2015-06-12 | E-GEOD-41297 | biostudies-arrayexpress

TRPS1 impairs myogenic differentiation in embryonal rhabdomyosarcoma [RNA-seq]

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TRPS1 impairs myogenic differentiation in embryonal rhabdomyosarcoma [ChIP-seq]

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