dc.contributor.author | Clark, Victoria E | |
dc.contributor.author | Harmancı, Akdes Serin | |
dc.contributor.author | Bai, Hanwen | |
dc.contributor.author | Youngblood, Mark W | |
dc.contributor.author | Lee, Tong Ihn | |
dc.contributor.author | Baranoski, Jacob F | |
dc.contributor.author | Ercan-Sencicek, A Gulhan | |
dc.contributor.author | Abraham, Brian J | |
dc.contributor.author | Weintraub, Abraham S | |
dc.contributor.author | Hnisz, Denes | |
dc.contributor.author | Simon, Matthias | |
dc.contributor.author | Krischek, Boris | |
dc.contributor.author | Erson-Omay, E Zeynep | |
dc.contributor.author | Henegariu, Octavian | |
dc.contributor.author | Carrión-Grant, Geneive | |
dc.contributor.author | Mishra-Gorur, Ketu | |
dc.contributor.author | Durán, Daniel | |
dc.contributor.author | Goldmann, Johanna E | |
dc.contributor.author | Schramm, Johannes | |
dc.contributor.author | Goldbrunner, Roland | |
dc.contributor.author | Piepmeier, Joseph M | |
dc.contributor.author | Vortmeyer, Alexander O | |
dc.contributor.author | Günel, Jennifer Moliterno | |
dc.contributor.author | Bilgüvar, Kaya | |
dc.contributor.author | Yasuno, Katsuhito | |
dc.contributor.author | Günel, Murat | |
dc.contributor.author | Young, Richard A. | |
dc.date.accessioned | 2017-05-01T19:11:16Z | |
dc.date.available | 2017-05-01T19:11:16Z | |
dc.date.issued | 2016-08 | |
dc.date.submitted | 2016-02 | |
dc.identifier.issn | 1061-4036 | |
dc.identifier.issn | 1546-1718 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/108555 | |
dc.description.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 SMO4 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. | en_US |
dc.language.iso | en_US | |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1038/ng.3651 | en_US |
dc.rights | Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. | en_US |
dc.source | PMC | en_US |
dc.title | Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Clark, Victoria E; Harmancı, Akdes Serin; Bai, Hanwen; Youngblood, Mark W; Lee, Tong Ihn; Baranoski, Jacob F; Ercan-Sencicek, A Gulhan and Abraham, Brian J. "Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas." Nature Genetics 48 (August 2016): 1253–1259. © 2016 Macmillan Publishers Limited, part of Springer Nature | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.mitauthor | Young, Richard A | |
dc.relation.journal | Nature Genetics | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Clark, Victoria E; Harmancı, Akdes Serin; Bai, Hanwen; Youngblood, Mark W; Lee, Tong Ihn; Baranoski, Jacob F; Ercan-Sencicek, A Gulhan; Abraham, Brian J; Weintraub, Abraham S; Hnisz, Denes; Simon, Matthias; Krischek, Boris; Erson-Omay, E Zeynep; Henegariu, Octavian; Carrión-Grant, Geneive; Mishra-Gorur, Ketu; Durán, Daniel; Goldmann, Johanna E; Schramm, Johannes; Goldbrunner, Roland; Piepmeier, Joseph M; Vortmeyer, Alexander O; Günel, Jennifer Moliterno; Bilgüvar, Kaya; Yasuno, Katsuhito; Young, Richard A; Günel, Murat | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8855-8647 | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |