ArticleCell reports2026
EWSR1::FLI1 promotes neocentromere formation in ewing sarcoma cells.
Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Abstract
Ewing sarcoma (EwS) is characterized by chimeric fusions such as EWSR1::FLI1. Chromosome gain or loss is prevalent in EwS, and this chromosome instability (CIN) phenotype correlates with poor treatment outcomes. We previously showed that CENP-A, a centromere-specific histone H3 variant, interacts with EWSR1 via its SYGQ2 motif, an interaction extending to the EWSR1::FLI1 fusion protein. CENP-A is highly expressed in EwS cells, driven by EWSR1::FLI1. EwS cells exhibit significant CIN, mitigated by depleting EWSR1::FLI1 or CENP-A, and frequently assemble neocentromeres. Using CENP-A ChIP-seq, we identify neocentromere-associated DNA sequences, and ChIP assays confirm EWSR1::FLI1 binds these sequences, suggesting EWSR1::FLI1 recruits CENP-A to drive neocentromere assembly. Notably, overexpressing EWSR1::FLI1, but not CENP-A, induces neocentromeres in non-EwS cells. These neocentromeres likely produce dicentric chromosomes, explaining the high incidence of chromosome bridges and chromoplexy underlying the CIN phenotype in EwS.
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