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Gene expression data of pHGG tumor samples

ABSTRACT: Pediatric high-grade gliomas (pHGGs) harboring the K27M mutation of H3F3A (histone H3.3) are characterized by global reduction of the repressive histone mark H3K27me3 and DNA hypomethylation. Analysis of K27M-induced changes on H3K27me3 occupancy and DNA methylation at differentially expresed genes (K27M vs. wild-type H3.3) in primary pHGG tumor samples.

ORGANISM(S): Homo sapiens

PROVIDER: GSE49822 | GEO | 2014/05/14

SECONDARY ACCESSION(S): PRJNA215022

REPOSITORIES: GEO

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Gene expression data of pHGG tumor samples

Project description:Pediatric high-grade gliomas (pHGGs) harboring the K27M mutation of H3F3A (histone H3.3) are characterized by global reduction of the repressive histone mark H3K27me3 and DNA hypomethylation. Analysis of K27M-induced changes on H3K27me3 occupancy and DNA methylation at differentially expresed genes (K27M vs. wild-type H3.3) in primary pHGG tumor samples. 22 glioblastoma samples from pHGG patients were selected for RNA extraction and hybridization on Affymetrix Affymetrix Human Genome U133 Plus 2.0 Arrays. Expression profiling data of 17 pHHGs are part of our previous study (GSE36245 or GSE34824).

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ena-DATASET-DKFZ-IBIOS-15-10-2013-14:26:06:568-481 - samples

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Project description:Recent studies have identified a Lys 27-to-methionine (K27M) mutation at one allele of H3F3A, one of the two genes encoding histone H3 variant H3.3, in 60% of high-grade pediatric glioma cases. The median survival of this group of patients after diagnosis is ∼1 yr. Here we show that the levels of H3K27 di- and trimethylation (H3K27me2 and H3K27me3) are reduced globally in H3.3K27M patient samples due to the expression of the H3.3K27M mutant allele. Remarkably, we also observed that H3K27me3 and Ezh2 (the catalytic subunit of H3K27 methyltransferase) at chromatin are dramatically increased locally at hundreds of gene loci in H3.3K27M patient cells. Moreover, the gain of H3K27me3 and Ezh2 at gene promoters alters the expression of genes that are associated with various cancer pathways. These results indicate that H3.3K27M mutation reprograms epigenetic landscape and gene expression, which may drive tumorigenesis. We performed chromatin-immunoprecipitation of H3K27me3, H3K4me3, and EZH2 in SF7761 and NSC cell lines. And do RNA-seq in SF7761, SF8828 and NSC cell lines. SF7761 and SF8628 cell lines from patients harboring the histone H3.3 K27M mutation were obtained from Hashizume et al. (2012). NSCs (N7800-100) were purchased from Invitrogen and cultured and maintained in NSC medium (A10509-01, StemPro NSC SFM, Invitrogen).

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