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Multi-omic and func...
Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions
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- Schöpf, Julia (author)
- Heidelberg University
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- Uhrig, Sebastian (author)
- German Cancer Research Centre
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- Heilig, Christoph E. (author)
- German Cancer Research Centre
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- Lee, Kwang Seok (author)
- German Cancer Research Centre
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- Walther, Tatjana (author)
- German Cancer Research Centre
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- Carazzato, Alexander (author)
- German Cancer Research Centre
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- Dobberkau, Anna Maria (author)
- German Cancer Research Centre
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- Weichenhan, Dieter (author)
- German Cancer Research Centre
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- Plass, Christoph (author)
- German Cancer Research Centre
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- Hartmann, Mark (author)
- German Cancer Research Centre
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- Diwan, Gaurav D. (author)
- Heidelberg University
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Carrero, Zunamys I. (author)
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Ball, Claudia R. (author)
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Hohl, Tobias (author)
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Kindler, Thomas (author)
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Rudolph-Hähnel, Patricia (author)
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Helm, Dominic (author)
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Schneider, Martin (author)
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- Nilsson, Anna (author)
- Karolinska Institutet
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- Øra, Ingrid (author)
- Lund University,Lunds universitet,Childhood Cancer Research Unit,Forskargrupper vid Lunds universitet,Cancercellers evolution,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,Pathways of cancer cell evolution,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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Imle, Roland (author)
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Banito, Ana (author)
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Russell, Robert B. (author)
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Jones, Barbara C. (author)
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Lipka, Daniel B. (author)
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Glimm, Hanno (author)
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Hübschmann, Daniel (author)
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Hartmann, Wolfgang (author)
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Fröhling, Stefan (author)
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Scholl, Claudia (author)
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Nature Communications. - 2041-1723. ; 15, s. 1-17
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Schöpf, Julia
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Uhrig, Sebastian
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Heilig, Christop ...
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Lee, Kwang Seok
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Walther, Tatjana
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Carazzato, Alexa ...
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show more...
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Dobberkau, Anna ...
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Weichenhan, Diet ...
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Plass, Christoph
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Hartmann, Mark
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Diwan, Gaurav D.
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Carrero, Zunamys ...
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Ball, Claudia R.
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Hohl, Tobias
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Kindler, Thomas
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Rudolph-Hähnel, ...
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Helm, Dominic
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Schneider, Marti ...
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Nilsson, Anna
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Øra, Ingrid
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Imle, Roland
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Banito, Ana
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Russell, Robert ...
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Jones, Barbara C ...
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Lipka, Daniel B.
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Glimm, Hanno
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Hübschmann, Dani ...
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Hartmann, Wolfga ...
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Fröhling, Stefan
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Scholl, Claudia
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Nature Communica ...
- By the university
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Lund University
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Karolinska Institutet