biostudies-literatureUnknownHofvander JNCI NIH HHSSynovial sarcoma (SyS) is an aggressive soft-tissue malignancy characterized by a pathognomonic chromosomal translocation leading to the formation of the SS18::SSX fusion oncoprotein. SS18::SSX associates with mammalian BAF complexes suggesting deregulation of chromatin architecture as the oncogenic driver in this tumour type. To examine the epigenomic state of SyS we performed comprehensive multi-omics analysis on 52 primary pre-treatment human SyS tumours. Our analysis revealed a continuum of epigenomic states across the cohort at fusion target genes independent of rare somatic genetic lesions. We identify cell-of-origin signatures defined by enhancer states and reveal unexpected relationships between H2AK119Ub1 and active marks. The number of bivalent promoters, dually marked by the repbioRxiv : the preprint server for biology2024.05.14.594262https://www.ebi.ac.uk/biostudies/studies/S-EPMC11118320biostudies-literatureSynovial Sarcoma Chromatin Dynamics Reveal a Continuum in SS18:SSX Reprograming.PMC11118320U54 CA231652Su EJones KBHill LAAndrulis ILMoksa MWunder JSLee KNielsen TOBanito AHofvander JGoytain AUnderhill TMSinger SMertens FBilenky MCarles AHirst MQiu ASotiriou ASteif JCao QfalseSynovial Sarcoma Chromatin Dynamics Reveal a Continuum in SS18:SSX Reprograming.Synovial sarcoma (SyS) is an aggressive soft-tissue malignancy characterized by a pathognomonic chromosomal translocation leading to the formation of the SS18::SSX fusion oncoprotein. SS18::SSX associates with mammalian BAF complexes suggesting deregulation of chromatin architecture as the oncogenic driver in this tumour type. To examine the epigenomic state of SyS we performed comprehensive multi-omics analysis on 52 primary pre-treatment human SyS tumours. Our analysis revealed a continuum of epigenomic states across the cohort at fusion target genes independent of rare somatic genetic lesions. We identify cell-of-origin signatures defined by enhancer states and reveal unexpected relationships between H2AK119Ub1 and active marks. The number of bivalent promoters, dually marked by the rep2024-01-01T00:00:00Z2024 May2026-07-02T03:16:55.054Z2026-07-02T03:11:38.144ZS-EPMC111183203879867210.1101/2024.05.14.594262