{"doi":"10.1016/j.celrep.2025.116376","title":"Origin of Ewing sarcoma by embryonic reprogramming of neural crest to mesoderm","abstract":"Ewing sarcoma is a malignant small round blue cell tumor caused by chromosomal translocations that generate aberrant fusion oncogenes, most frequently EWSR1::FLI1. The cell of origin and mechanisms of EWSR1::FLI1-driven transformation have remained unresolved, largely due to the lack of a representative animal model. Using a zebrafish genetic Ewing sarcoma model, we provide evidence for a neural crest origin of this cancer. Neural crest-derived cells uniquely tolerate expression of EWSR1::FLI1, and targeted expression of EWSR1::FLI1 in these cells generates lethal Ewing sarcomas. Single-cell analysis of tumor initiation shows that EWSR1::FLI1 reprograms neural crest-derived cells to a mesoderm-like state, strikingly resulting in ectopic fins throughout the body. By profiling chromatin accessibility and genome-wide EWSR1::FLI1 binding, we find that the fusion oncogene hijacks developmental enhancers for neural crest to mesoderm reprogramming during cancer initiation. These findings show how a single mutation profoundly alters embryonic cell fate decisions to initiate a devastating childhood cancer.","journal":"Cell Reports","year":2025,"id":522198,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":344764,"name":"Claire Arata","orcid":"0000-0003-1535-1818","position":1,"is_corresponding":false},{"id":305997,"name":"Yongfeng Luo","orcid":"0000-0001-8765-0273","position":2,"is_corresponding":false},{"id":1394175,"name":"Rubén Burgos","orcid":null,"position":3,"is_corresponding":false},{"id":344765,"name":"J. Gage Crump","orcid":"0000-0002-3209-0026","position":4,"is_corresponding":false},{"id":7765,"name":"James F. Amatruda","orcid":"0000-0002-9901-2137","position":5,"is_corresponding":false},{"id":704581,"name":"Elena Vasileva","orcid":"0000-0003-2026-1331","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T02:49:54.058858Z","pmid":"41072418","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}