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

·发布 2016年8月21日 ·更新 2016年9月12日

样本数

实验数

实验描述

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)

样本属性

age

42, 43, 48, 50, 53, 61, 62, 66, 67, 68, 71, 73, 76, 78, U

histology

fibrous, meningothelial, psammomatous, secretory, secretory+meningothelial, unknown

mutation group

AKT1/TRAF7, KLF4/TRAF7, NF2/Chr22_Loss, POLR2A

organism

Homo sapiens

organism part

meninges, Meningioma

radiated

N, U, Y

sex

female, male

who grade

实验信息

登记号

E-GEOD-85133

GEO 编号

SRP080850, GSE85133

实验类型

RNA-seq of coding RNA

物种

Homo sapiens

发布日期

2016年8月21日

更新日期

2016年9月12日

提交者

Matthias Simon、 E Z Erson-Omay、 Abraham S Weintraub、 Boris Krischek、 Richard A Young、 Mark W Youngblood、 Johannes Schramm、 Daniel Durán、 Kaya Bilgüvar、 Murat Günel、 Victoria Elizabeth Clark、 Tong I Lee、 Octavian Henegariu、 Ketu Mishra-Goru、 Hanwen Bai、 Katsuhito Yasuno、 Joseph M Piepmeier、 Akdes Serin Harmancı、 Geneive Carrión-Grant、 Jennifer M Günel、 Jacob Baranoski、 Victoria E Clark、 Brian J Abraham、 Roland Goldbrunner、 Denes Hnisz、 Alexander O Vortmeyer、 Johanna E Goldmann、 Adife G Ercan-Sencicek

外部链接

ArrayExpress 原始页 NCBI GEO：SRP080850, GSE85133

分析服务

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

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