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C11orf95–RELA fusions drive oncogenic NF-κB signalling in ependymoma
Open accessAbstract
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.
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Metadata
- Authors
- Parker, M., Mohankumar, K. M., Punchihewa, C., Weinlich, R., Dalton, J. D., Li, Y., Lee, R., Tatevossian, R. G., Phoenix, T. N., Thiruvenkatam, R., White, E., Tang, B., Orisme, W., Gupta, K., Rusch, M., Chen, X., Li, Y., Nagahawhatte, P., Hedlund, E., Finkelstein, D., Wu, G., Shurtleff, S., Easton, J., Boggs, K., Yergeau, D., Vadodaria, B., Mulder, H. L., Becksfort, J., Gupta, P., Huether, R., Ma, J., Song, G., Gajjar, A., Merchant, T., Boop, F., Smith, A. A., Ding, L., Lu, C., Ochoa, K., Zhao, D., Fulton, R. S., Fulton, L. L., Mardis, E. R., Wilson, R. K., Downing, J. R., Green, D. R., Zhang, J., Ellison, D. W., & Gilbertson, R. J.
- Venue
- Nature
- Published
- 2014-02-19
- Volume
- 506
- Issue
- 7489
- Pages
- 451-455
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1976979641
- Cited by
- 670
- References
- 2
- FWCI
- 19.54
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: C11orf95–RELA fusions drive oncogenic NF-κB signalling in ependymoma. https://app.cochat.ai/papers/10.1038/nature13109
- The paper
- Parker, M., Mohankumar, K. M., Punchihewa, C., Weinlich, R., Dalton, J. D., Li, Y., Lee, R., Tatevossian, R. G., Phoenix, T. N., Thiruvenkatam, R., White, E., Tang, B., Orisme, W., Gupta, K., Rusch, M., Chen, X., Li, Y., Nagahawhatte, P., Hedlund, E., . . . Gilbertson, R. J. (2014). C11orf95–RELA fusions drive oncogenic NF-κB signalling in ependymoma. Nature. https://doi.org/10.1038/nature13109
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
