 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 21, 2016 |
| Title |
Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas [array] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations in this enzyme have not been previously linked to any pathology in humans, a testament to its indispensable role in cell biology. Based on 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, are sufficient to hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors reveal dysregulation of key meningeal identity genes, including WNT6 and ZIC1/ZIC4. In addition to 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.
|
| |
|
| Overall design |
Expression microarray data from 121 total samples, including 96 tumors representing the major meningioma mutation groups (NF2/chr22 loss, POLR2A, KLF4/TRAF7, PI3K mutant, Sonic Hedgehog mutant) and 25 control samples (3 dura, 13 adult meninges, and 9 embryonic meninges).
|
| |
|
| Contributor(s) |
Clark VE, Serin Harmancı A, Bai H, Youngblood MW, Lee TI, Baranoski J, Ercan-Sencicek AG, Abraham BJ, Weintraub AS, Hnisz D, Simon M, Krischek B, Erson-Omay EZ, Henegariu O, Carrión-Grant G, Mishra-Goru K, Durán D, Goldmann JE, Schramm J, Goldbrunner R, Piepmeier JM, Vortmeyer AO, Günel JM, Bilgüvar K, Yasuno K, Young RA, Günel M |
| Citation(s) |
27548314, 28195122, 37805627 |
| |
| Submission date |
Jul 11, 2016 |
| Last update date |
Oct 25, 2023 |
| Contact name |
Victoria Elizabeth Clark |
| E-mail(s) |
victoria.clark@yale.edu
|
| Organization name |
Yale University School of Medicine
|
| Department |
Departments of Neurosurgery and Genetics
|
| Lab |
Murat Gunel
|
| Street address |
300 Cedar Street TAC S330
|
| City |
New Haven |
| State/province |
CT |
| ZIP/Postal code |
06520 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
|
| Samples (121)
|
|
| This SubSeries is part of SuperSeries: |
| GSE85135 |
Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas |
|
| Relations |
| BioProject |
PRJNA328491 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE84263_Non-normalized_data.txt.gz |
25.6 Mb |
(ftp)(http) |
TXT |
| GSE84263_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...