GEO series

Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition

GSE43392 Homo sapiens (human) Expression microarray 12 samples Submitted 2013/02/25 Platform GPL15207

At a glance

Expression microarray · human · 12 samples

What it is: Expression microarrayGene activity read on a chip (the older technology that RNA-seq replaced).
Organism: Homo sapiens (human)
Topic: NeuroblastomaThis series is part of our curated briefing on it.
Samples: 12 samples
Data you can get: A processed expression table (series matrix) and the array files, from NCBI.

Summary (written by the submitters)

Bromodomain inhibition comprises a promising therapeutic strategy in cancer, particularly for hematologic malignancies. To date, however, genomic biomarkers to direct clinical translation have been lacking. We conducted a cell-based screen of genetically-defined cancer cell lines using a prototypical inhibitor of BET bromodomains. Integration of genetic features with chemosensitivity data revealed a robust correlation between MYCN amplification and sensitivity to bromodomain inhibition.

Read the full summary ↓

We characterized the mechanistic and translational significance of this finding in neuroblastoma, a childhood cancer with frequent amplification of MYCN. Genome-wide expression analysis demonstrated downregulation of the MYCN transcriptional program accompanied by suppression of MYCN transcription. Functionally, bromodomain-mediated inhibition of MYCN impaired growth and induced apoptosis in neuroblastoma. BRD4 knock-down phenocopied these effects, establishing BET bromodomains as transcriptional regulators of MYCN. BET inhibition conferred a significant survival advantage in three in vivo neuroblastoma models, providing a compelling rationale for developing BET bromodomain inhibitors in patients with neuroblastoma. Significance: Biomarkers of response to small-molecule inhibitors of BET bromodomains, a new compound class with promising anti-cancer activity, have been lacking. Here, we reveal MYCN amplification as a strong genetic predictor of sensitivity to BET bromodomain inhibitors, demonstrate a mechanistic rationale for this finding, and provide a translational framework for clinical trial development of BET bromodomain inhibitors for pediatric patients with MYCN-amplified neuroblastoma.

This dataset

Open GSE43392 in finder → Find more human microarray datasets → Neuroblastoma landscape →

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 (GSE43392_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 PRJNA185813. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 23430699) ↗

Samples in this study

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+ 12 more — browse all 12 samples with per-sample file links →

More Neuroblastoma datasets

GSE112914 Differential gene expression analysis of MYCN-amplified neuroblastoma cells after Doxycycline inducible shRNA knockdown of JMJD6 gene expression 44 samples same disease briefing · shares mycn, neuroblastoma
GSE181582 IGF2BP1 induces neuroblastoma via a druggable feedforward loop with MYCN promoting 17q oncogene expression 264 samples same disease briefing · shares mycn, neuroblastoma
GSE164456 Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma 69 samples same disease briefing · shares mycn, neuroblastoma
GSE167478 MYCN directly regulates TET1 expression to control 5-hmC distribution and enhance neuroblastoma cell migration in hypoxia 22 samples same disease briefing · shares mycn, neuroblastoma
GSE167475 MYCN directly regulates TET1 expression to control 5-hmC distribution and enhance neuroblastoma cell migration in hypoxia [hMe-SEAL] 7 samples same disease briefing · shares mycn, neuroblastoma
GSE275538 Identification of EPLIN as a novel MYCN-independent target in neuroblastoma and medulloblastoma 1 samples same disease briefing · shares mycn, neuroblastoma
GSE120572 A mechanistic classification of clinical phenotypes in neuroblastoma 394 samples same disease briefing · shares neuroblastoma
GSE16476 Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma 88 samples same disease briefing · shares neuroblastoma

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