PUBLICATION
Functional Genomics of Novel Rhabdomyosarcoma Fusion-Oncogenes Using Zebrafish
- Authors
- Kent, M.R., Silvius, K., Kucinski, J., Calderon, D., Kendall, G.C.
- ID
- ZDB-PUB-230906-52
- Date
- 2024
- Source
- Methods in molecular biology (Clifton, N.J.) 2707: 234123-41 (Journal)
- Registered Authors
- Kendall, Genevieve
- Keywords
- Functional genomics, Fusion-oncogene, Pediatric sarcoma, Rhabdomyosarcoma, Zebrafish cancer models
- MeSH Terms
-
- Animals
- Carcinogenesis
- Cell Transformation, Neoplastic
- Genomics
- Humans
- Oncogenes
- Rhabdomyosarcoma*/genetics
- Zebrafish*/genetics
- PubMed
- 37668903 Full text @ Meth. Mol. Biol.
Citation
Kent, M.R., Silvius, K., Kucinski, J., Calderon, D., Kendall, G.C. (2024) Functional Genomics of Novel Rhabdomyosarcoma Fusion-Oncogenes Using Zebrafish. Methods in molecular biology (Clifton, N.J.). 2707:234123-41.
Abstract
Clinical sequencing efforts continue to identify novel putative oncogenes with limited strategies to perform functional validation in vivo and study their role in tumorigenesis. Here, we present a pipeline for fusion-driven rhabdomyosarcoma (RMS) in vivo modeling using transgenic zebrafish systems. This strategy originates with novel fusion-oncogenes identified from patient samples that require functional validation in vertebrate systems, integrating these genes into the zebrafish genome, and then characterizing that they indeed drive rhabdomyosarcoma tumor formation. In this scenario, the human form of the fusion-oncogene is inserted into the zebrafish genome to understand if it is an oncogene, and if so, the underlying mechanisms of tumorigenesis. This approach has been successful in our models of infantile rhabdomyosarcoma and alveolar rhabdomyosarcoma, both driven by respective fusion-oncogenes, VGLL2-NCOA2 and PAX3-FOXO1. Our described zebrafish platform is a rapid method to understand the impact of fusion-oncogene activity, divergent and shared fusion-oncogene biology, and whether any analyzed pathways converge for potential clinically actionable targets.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping