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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-02

AUTHORS

Matthew Parker, Kumarasamypet M. Mohankumar, Chandanamali Punchihewa, Ricardo Weinlich, James D. Dalton, Yongjin Li, Ryan Lee, Ruth G. Tatevossian, Timothy N. Phoenix, Radhika Thiruvenkatam, Elsie White, Bo Tang, Wilda Orisme, Kirti Gupta, Michael Rusch, Xiang Chen, Yuxin Li, Panduka Nagahawhatte, Erin Hedlund, David Finkelstein, Gang Wu, Sheila Shurtleff, John Easton, Kristy Boggs, Donald Yergeau, Bhavin Vadodaria, Heather L. Mulder, Jared Becksfort, Pankaj Gupta, Robert Huether, Jing Ma, Guangchun Song, Amar Gajjar, Thomas Merchant, Frederick Boop, Amy A. Smith, Li Ding, Charles Lu, Kerri Ochoa, David Zhao, Robert S. Fulton, Lucinda L. Fulton, Elaine R. Mardis, Richard K. Wilson, James R. Downing, Douglas R. Green, Jinghui Zhang, David W. Ellison, Richard J. Gilbertson

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. More... »

PAGES

451

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature13109

DOI

http://dx.doi.org/10.1038/nature13109

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050781394

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24553141


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