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The SWI/SNF complex member SMARCB1 supports lineage fidelity in kidney cancer.
Wesolowski, Ludovic; Ge, Jianfeng; Castillon, Leticia; Sesia, Debora; Dyas, Anna; Hirosue, Shoko; Caraffini, Veronica; Warren, Anne Y; Rodrigues, Paulo; Ciriello, Giovanni; Patel, Saroor A; Vanharanta, Sakari.
Afiliación
  • Wesolowski L; MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
  • Ge J; MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
  • Castillon L; Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK.
  • Sesia D; Translational Cancer Medicine Program, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland.
  • Dyas A; Department of Computational Biology, University of Lausanne (UNIL), 1015 Lausanne, Switzerland.
  • Hirosue S; Swiss Cancer Center Leman, Lausanne, Switzerland.
  • Caraffini V; MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
  • Warren AY; Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK.
  • Rodrigues P; MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
  • Ciriello G; MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
  • Patel SA; Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
  • Vanharanta S; MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.
iScience ; 26(8): 107360, 2023 Aug 18.
Article en En | MEDLINE | ID: mdl-37554444
Lineage switching can induce therapy resistance in cancer. Yet, how lineage fidelity is maintained and how it can be lost remain poorly understood. Here, we have used CRISPR-Cas9-based genetic screening to demonstrate that loss of SMARCB1, a member of the SWI/SNF chromatin remodeling complex, can confer an advantage to clear cell renal cell carcinoma (ccRCC) cells upon inhibition of the renal lineage factor PAX8. Lineage factor inhibition-resistant ccRCC cells formed tumors with morphological features, but not molecular markers, of neuroendocrine differentiation. SMARCB1 inactivation led to large-scale loss of kidney-specific epigenetic programs and restoration of proliferative capacity through the adoption of new dependencies on factors that represent rare essential genes across different cancers. We further developed an analytical approach to systematically characterize lineage fidelity using large-scale CRISPR-Cas9 data. An understanding of the rules that govern lineage switching could aid the development of more durable lineage factor-targeted and other cancer therapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos