Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-10

AUTHORS

Victoria E Clark, Akdes Serin Harmancı, Hanwen Bai, Mark W Youngblood, Tong Ihn Lee, Jacob F Baranoski, A Gulhan Ercan-Sencicek, Brian J Abraham, Abraham S Weintraub, Denes Hnisz, Matthias Simon, Boris Krischek, E Zeynep Erson-Omay, Octavian Henegariu, Geneive Carrión-Grant, Ketu Mishra-Gorur, Daniel Durán, Johanna E Goldmann, Johannes Schramm, Roland Goldbrunner, Joseph M Piepmeier, Alexander O Vortmeyer, Jennifer Moliterno Günel, Kaya Bilgüvar, Katsuhito Yasuno, Richard A Young, Murat Günel

ABSTRACT

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes, including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO, we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features. More... »

PAGES

1253-1259

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3651

    DOI

    http://dx.doi.org/10.1038/ng.3651

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1005736302

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27548314


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