The hegemonic EWSR1::ETS oncoprotein overrules core regulatory circuitry principles in Ewing sarcoma.

ABSTRACT: Ewing sarcoma is an aggressive bone tumor of adolescence characterized by a hallmark EWSR1::ETS fusion oncogene. The resulting chimeric oncoprotein drives tumorigenesis by reshaping transcriptional and epigenetic landscapes. However, how it is transcriptionally regulated and whether additional master transcription factors (MTFs) form a core regulatory circuit (CRC) in Ewing sarcoma remain unclear. Using an extensive panel of Ewing sarcoma cell lines and primary tumors, we mapped super-enhancers and identified enrichment of GGAA microsatellites, confirming their specificity to Ewing sarcoma as compared to other pediatric cancers and normal tissues. Integrating transcriptomic, epigenetic, 3D chromatin conformation, and dependency data, we predicted a set of MTFs potentially forming a CRC. Ho

SUBMITTER: Grossetete S 

PROVIDER: S-EPMC12819515 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature