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| Verfasst von: | Ellermann, Julia [VerfasserIn]  |
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| | Uhrig, Sebastian [VerfasserIn] |
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| | Heilig, Christoph E. [VerfasserIn] |
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| | Lee, Kwang Seok [VerfasserIn] |
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| | Walther, Tatjana [VerfasserIn] |
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| | Carazzato, Alexander [VerfasserIn] |
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| | Dobberkau, Anna Maria [VerfasserIn] |
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| | Weichenhan, Dieter [VerfasserIn] |
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| | Plass, Christoph [VerfasserIn] |
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| | Hartmann, Mark [VerfasserIn] |
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| | Diwan, Gaurav [VerfasserIn] |
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| | Carrero, Zunamys I. [VerfasserIn] |
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| | Ball, Claudia R. [VerfasserIn] |
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| | Hohl, Tobias [VerfasserIn] |
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| | Kindler, Thomas [VerfasserIn] |
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| | Rudolph-Hähnel, Patricia [VerfasserIn] |
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| | Helm, Dominic [VerfasserIn] |
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| | Schneider, Martin [VerfasserIn] |
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| | Nilsson, Anna [VerfasserIn] |
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| | Øra, Ingrid [VerfasserIn] |
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| | Imle, Roland [VerfasserIn] |
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| | Banito, Ana [VerfasserIn] |
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| | Russell, Robert B. [VerfasserIn] |
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| | Jones, Barbara Christine [VerfasserIn] |
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| | Lipka, Daniel [VerfasserIn] |
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| | Glimm, Hanno [VerfasserIn] |
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| | Hübschmann, Daniel [VerfasserIn] |
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| | Hartmann, Wolfgang [VerfasserIn] |
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| | Fröhling, Stefan [VerfasserIn] |
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| | Scholl, Claudia [VerfasserIn] |
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| Titel: | Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions |
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| Verf.angabe: | Julia Schöpf, Sebastian Uhrig, Christoph E. Heilig, Kwang-Seok Lee, Tatjana Walther, Alexander Carazzato, Anna Maria Dobberkau, Dieter Weichenhan, Christoph Plass, Mark Hartmann, Gaurav D. Diwan, Zunamys I. Carrero, Claudia R. Ball, Tobias Hohl, Thomas Kindler, Patricia Rudolph-Hähnel, Dominic Helm, Martin Schneider, Anna Nilsson, Ingrid Øra, Roland Imle, Ana Banito, Robert B. Russell, Barbara C. Jones, Daniel B. Lipka, Hanno Glimm, Daniel Hübschmann, Wolfgang Hartmann, Stefan Fröhling, Claudia Scholl |
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| E-Jahr: | 2024 |
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| Jahr: | 02 January 2024 |
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| Umfang: | 17 S. |
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| Fussnoten: | Gesehen am 30.01.2024 |
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| Titel Quelle: | Enthalten in: Nature Communications |
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| Ort Quelle: | [London] : Springer Nature, 2010 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 15(2024), Artikel-ID 51, Seite 1-17 |
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| ISSN Quelle: | 2041-1723 |
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| Abstract: | Linking clinical multi-omics with mechanistic studies may improve the understanding of rare cancers. We leverage two precision oncology programs to investigate rhabdomyosarcoma with FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective therapies. All tumors exhibit outlier ALK expression, partly accompanied by intragenic deletions and aberrant splicing resulting in ALK variants that are oncogenic and sensitive to ALK inhibitors. Additionally, recurrent CKDN2A/MTAP co-deletions provide a rationale for PRMT5-targeted therapies. Functional studies show that FUS-TFCP2 blocks myogenic differentiation, induces transcription of ALK and truncated TERT, and inhibits DNA repair. Unlike other fusion-driven sarcomas, TFCP2-rearranged tumors exhibit genomic instability and signs of defective homologous recombination. DNA methylation profiling demonstrates a close relationship with undifferentiated sarcomas. In two patients, sarcoma was preceded by benign lesions carrying FUS-TFCP2, indicating stepwise sarcomagenesis. This study illustrates the potential of linking precision oncology with preclinical research to gain insight into the classification, pathogenesis, and therapeutic vulnerabilities of rare cancers. |
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| DOI: | doi:10.1038/s41467-023-44360-2 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1038/s41467-023-44360-2 |
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| | Volltext: https://www.nature.com/articles/s41467-023-44360-2 |
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| | DOI: https://doi.org/10.1038/s41467-023-44360-2 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Cancer genomics |
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| | Mechanisms of disease |
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| | Oncogenesis |
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| | Sarcoma |
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| K10plus-PPN: | 1879507374 |
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| Verknüpfungen: | → Zeitschrift |
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Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions / Ellermann, Julia [VerfasserIn]; 02 January 2024 (Online-Ressource)
