| Literature DB >> 27548314 |
Victoria E Clark1,2,3, Akdes Serin Harmancı1,2, Hanwen Bai1,3, Mark W Youngblood1,2,3, Tong Ihn Lee4, Jacob F Baranoski1,2,3, A Gulhan Ercan-Sencicek2,5, Brian J Abraham4, Abraham S Weintraub4, Denes Hnisz4, Matthias Simon6, Boris Krischek7, E Zeynep Erson-Omay1,2, Octavian Henegariu1,2,3,5,8, Geneive Carrión-Grant1,2, Ketu Mishra-Gorur1,2,3,5,8, Daniel Durán1,2,3, Johanna E Goldmann4, Johannes Schramm9, Roland Goldbrunner7, Joseph M Piepmeier2, Alexander O Vortmeyer10, Jennifer Moliterno Günel1,2, Kaya Bilgüvar1,3,11, Katsuhito Yasuno1,2, Richard A Young4,12, Murat Günel1,2,3,5,8,13.
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.Entities:
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Year: 2016 PMID： 27548314 PMCID： PMC5114141 DOI： 10.1038/ng.3651
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330