Unknown,Transcriptomics,Genomics,Proteomics

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Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas [RNA-seq]


ABSTRACT: 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. RNAseq data from 19 meningioma tumors representing major mutation groups (NF2/chr22 loss, POLR2A, KLF4/TRAF7, PI3K mutant)

ORGANISM(S): Homo sapiens

SUBMITTER: Victoria Clark 

PROVIDER: E-GEOD-85133 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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