Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas
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Author(s)
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
Date Issued
August 2016
Journal
Nature Genetics
Publisher
Nature Publishing Group
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
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Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1038/ng.3651
