GEO series

Gene expression profiling of EZH2 mutant and wild type DLBCL cell lines treated with EZH2 inhibitor

GSE40971 Homo sapiens (human) Expression microarray 40 samples Submitted 2012/10/12 Platform GPL570

At a glance

Expression microarray · human · 40 samples

What it is: Expression microarrayGene activity read on a chip (the older technology that RNA-seq replaced).
Organism: Homo sapiens (human)
Topic: Diffuse large B-cell lymphomaThis series is part of our curated briefing on it.
Samples: 40 samples
Data you can get: A processed expression table (series matrix) and the array files, from NCBI.

Summary (written by the submitters)

We studied transcriptional changes by Affymetrix human microarrays in DLBCL cell lines as a result of treatment with GSK126, a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2 In eukaryotes, epigenetic post-translational modification of histones is critical for regulation of chromatin structure and gene expression.

Read the full summary ↓

EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) and is responsible for repressing target gene expression through methylation of histone H3 on lysine 27 (H3K27). Over-expression of EZH2 is implicated in tumorigenesis and correlates with poor prognosis in multiple tumor types. Recent reports have identified somatic heterozygous mutations of Y641 and A677 residues within the catalytic SET domain of EZH2 in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The Y641 residue is the most frequently mutated residue, with 22% of GCB (Germinal Cell B-cell) DLBCL and FL harboring mutations at this site. These lymphomas exhibit increased H3K27 tri-methylation (H3K27me3) due to altered substrate preferences of the mutant enzymes. However, it is unknown whether direct inhibition of EZH2 methyltransferase activity alone will be effective in treating lymphomas carrying activating EZH2 mutations. Herein, we demonstrate that GSK126, a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2 methyltransferase activity, decreases global H3K27me3 levels and reactivates silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and dramatically inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Together, these data demonstrate that pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma.

This dataset

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Download · which file do I need?

Direct links to NCBI, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need.

All supplementary files ↗

3 · The original raw files

Whole study · RAW.tar

Everything the authors deposited as one archive (GSE40971_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

Whole study · RAW.tar ↓

What the files usually look like: For arrays the series matrix is normally the normalised expression table you want; the raw array files (CEL and similar) are in the RAW.tar.

Also filed as BioProject PRJNA175452. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 23051747) ↗

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 40 more — browse all 40 samples with per-sample file links →

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GSE11318 Molecular subtypes of DLBCL have distinct chromosomal aberrations 406 samples same disease briefing · shares dlbcl, type
GSE231624 (1) Effect of KLHL6 loss on the transcriptome in DLBCL upon NOTCH ligand stimulation. (2) Effect of KLHL6 and NOTCH2 loss on the transcriptome in DLBCL. (3) Effect of DLBCL-associated NOTCH2 mutants on the transcriptome in DLBCL. 48 samples same disease briefing · shares dlbcl, mutant
GSE224867 RNA-seq analysis of DLBCL cell lines in response to chemotherapy 36 samples same disease briefing · shares dlbcl, lines
GSE280799 Expression Data from DLBCL Cell Line U2932 (Parental, CDC-Treated, and CDC-Resistant) and 8 DLBCL Patient Samples (5 High CDC-Sensitive, 3 Low CDC-Sensitive) 20 samples same disease briefing · shares dlbcl, treated
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