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C11orf95–RELA fusions drive oncogenic NF-κB signalling in ependymoma

Author

Listed:
  • Matthew Parker

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

  • Kumarasamypet M. Mohankumar

    (St. Jude Children’s Research Hospital)

  • Chandanamali Punchihewa

    (St. Jude Children’s Research Hospital)

  • Ricardo Weinlich

    (St. Jude Children’s Research Hospital)

  • James D. Dalton

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

  • Yongjin Li

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

  • Ryan Lee

    (St. Jude Children’s Research Hospital)

  • Ruth G. Tatevossian

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

  • Timothy N. Phoenix

    (St. Jude Children’s Research Hospital)

  • Radhika Thiruvenkatam

    (St. Jude Children’s Research Hospital)

  • Elsie White

    (St. Jude Children’s Research Hospital)

  • Bo Tang

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

  • Wilda Orisme

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

  • Kirti Gupta

    (St. Jude Children’s Research Hospital)

  • Michael Rusch

    (St. Jude Children’s Research Hospital)

  • Xiang Chen

    (St. Jude Children’s Research Hospital)

  • Yuxin Li

    (St. Jude Children’s Research Hospital
    Structural Biology, St. Jude Children’s Research Hospital)

  • Panduka Nagahawhatte

    (St. Jude Children’s Research Hospital)

  • Erin Hedlund

    (St. Jude Children’s Research Hospital)

  • David Finkelstein

    (St. Jude Children’s Research Hospital)

  • Gang Wu

    (St. Jude Children’s Research Hospital)

  • Sheila Shurtleff

    (St. Jude Children’s Research Hospital)

  • John Easton

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

  • Kristy Boggs

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project)

  • Donald Yergeau

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project)

  • Bhavin Vadodaria

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project)

  • Heather L. Mulder

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project)

  • Jared Becksfort

    (St. Jude Children’s Research Hospital)

  • Pankaj Gupta

    (St. Jude Children’s Research Hospital)

  • Robert Huether

    (Structural Biology, St. Jude Children’s Research Hospital)

  • Jing Ma

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project)

  • Guangchun Song

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project)

  • Amar Gajjar

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

  • Thomas Merchant

    (St. Jude Children’s Research Hospital)

  • Frederick Boop

    (St. Jude Children’s Research Hospital)

  • Amy A. Smith

    (MD Anderson Cancer Center Orlando, Pediatric Hematology/Oncology, 92 West Miller MP 318, Orlando, Florida 32806, USA)

  • Li Ding

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    The Genome Institute, Washington University School of Medicine in St Louis
    Washington University School of Medicine in St Louis)

  • Charles Lu

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    The Genome Institute, Washington University School of Medicine in St Louis)

  • Kerri Ochoa

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    The Genome Institute, Washington University School of Medicine in St Louis
    Washington University School of Medicine in St Louis)

  • David Zhao

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

  • Robert S. Fulton

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    The Genome Institute, Washington University School of Medicine in St Louis)

  • Lucinda L. Fulton

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    The Genome Institute, Washington University School of Medicine in St Louis
    Washington University School of Medicine in St Louis)

  • Elaine R. Mardis

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    The Genome Institute, Washington University School of Medicine in St Louis
    Washington University School of Medicine in St Louis
    Siteman Cancer Center, Washington University School of Medicine in St Louis)

  • Richard K. Wilson

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    The Genome Institute, Washington University School of Medicine in St Louis
    Washington University School of Medicine in St Louis
    Siteman Cancer Center, Washington University School of Medicine in St Louis)

  • James R. Downing

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

  • Douglas R. Green

    (St. Jude Children’s Research Hospital)

  • Jinghui Zhang

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

  • David W. Ellison

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

  • Richard J. Gilbertson

    (St. Jude Children’s Research Hospital - Washington University Pediatric Cancer Genome Project
    St. Jude Children’s Research Hospital)

Abstract

Members of the nuclear factor-κB (NF-κB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-κB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-κB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-κB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95–RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95–RELA fusion proteins translocated spontaneously to the nucleus to activate NF-κB target genes, and rapidly transformed neural stem cells—the cell of origin of ependymoma—to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95–RELA fusion protein as a potential therapeutic target in supratentorial ependymoma.

Suggested Citation

  • Matthew Parker & Kumarasamypet M. Mohankumar & Chandanamali Punchihewa & Ricardo Weinlich & James D. Dalton & Yongjin Li & Ryan Lee & Ruth G. Tatevossian & Timothy N. Phoenix & Radhika Thiruvenkatam &, 2014. "C11orf95–RELA fusions drive oncogenic NF-κB signalling in ependymoma," Nature, Nature, vol. 506(7489), pages 451-455, February.
    • Handle: RePEc:nat:nature:v:506:y:2014:i:7489:d:10.1038_nature13109
    DOI: 10.1038/nature13109
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    Citations

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    Cited by:

    1. Konstantin Okonechnikov & Aylin Camgöz & Owen Chapman & Sameena Wani & Donglim Esther Park & Jens-Martin Hübner & Abhijit Chakraborty & Meghana Pagadala & Rosalind Bump & Sahaana Chandran & Katerina K, 2023. "3D genome mapping identifies subgroup-specific chromosome conformations and tumor-dependency genes in ependymoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Fengju Chen & Yiqun Zhang & Lanlan Shen & Chad J. Creighton, 2024. "The DNA methylome of pediatric brain tumors appears shaped by structural variation and predicts survival," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Min Kyung Lee & Nasim Azizgolshani & Joshua A. Shapiro & Lananh N. Nguyen & Fred W. Kolling & George J. Zanazzi & Hildreth Robert Frost & Brock C. Christensen, 2024. "Identifying tumor type and cell type-specific gene expression alterations in pediatric central nervous system tumors," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Yanling Liu & Jonathon Klein & Richa Bajpai & Li Dong & Quang Tran & Pandurang Kolekar & Jenny L. Smith & Rhonda E. Ries & Benjamin J. Huang & Yi-Cheng Wang & Todd A. Alonzo & Liqing Tian & Heather L., 2023. "Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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