Authors
Holly J Whitfield, Nathaniel D Anderson, Christina Burke, Marian J Groot Koerkamp, Conor Parks, Toochi Ogbonnah, Yvette Wood, Alice Piapi, Emilia Robertson, Eleanor Watt, Abigail White, Solange De Noon, Jonathan Kennedy, Rajvi Nagrecha, Michael T Meister, Ewa Aladowicz, Yang Kee Stella Man, Virginia Laspidea, Mi K Trinh, Angus Hodder, Tarryn Porter, John E Lawrence, Elizabeth Tuck, Trung Nguyen, Anna Kelsey, Adrienne M Flanagan, Richard Hewitt, Naima Smeulders, Olga Slater, J Ciaran Hutchinson, Neil Sebire, Janet M Shipley, Jarno Drost, Karin Straathof, Sam Behjati
Published in
Cancer research. Jul 14, 2026. Epub Jul 14, 2026.
Abstract
Somatic mutations often predict survival in childhood cancers, as exemplified in rhabdomyosarcoma, where FOXO1 gene fusion status is a key prognostic feature. Here, we examined single-cell transcriptomics and discovered that cancer cells of lethal disease converge on a common cell state with a shared transcriptional landscape, irrespective of fusion status. Nuclear transcriptomics, chromatin accessibility, spatial transcriptomics, perturbation studies, and previously published data sets validated the overarching high-risk cell state. The convergent cell state only partially overlapped with transcriptional effects of the FOXO1 fusion and unexpectedly exhibited neural features. Overall, these findings delineate a cell state of high-risk rhabdomyosarcoma cells that transcends conventional molecular and histological boundaries, suggesting an overarching disease phenotype that could transform target discovery and inform clinical practice.
PMID:
42446905
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.
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