Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas [array]

·发布 2016年8月21日 ·更新 2016年9月12日

121

样本数

121

实验数

芯片平台

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. 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).

芯片平台

A-GEOD-10558

Illumina HumanHT-12 V4.0 expression beadchip（121 例）

样本属性

batch

1, 10, 2, 3, 4, 5, 6, 9

grade

1, NA

mutation group

AKT1, AKT1/TRAF7, AKT1/TRAF7/Chr*loss, Chr22_Loss, KLF4/TRAF7, KLF4/TRAF7/Chr*amp, NF2/Chr22, NF2/Chr22_Loss, NF2/Chr22_Loss/3p, NF2/SMARCB1/Chr22_Loss, PIK3CA, PIK3CA/TRAF7, POLR2A, PRKAR1A, SMARCB1, SMARCB1/NF2, SMO L412F, SMO W535L, SUFU, TRAF7

organism

Homo sapiens

organism part

meninges, Meningioma

primary status

Primary

radiation

实验信息

登记号

E-GEOD-84263

GEO 编号

GSE84263

实验类型

transcription profiling by array

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

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

外部链接

ArrayExpress 原始页 NCBI GEO：GSE84263

分析服务

Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas [array]

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