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Combined inhibition of histone methyltransferases EZH2 and DOT1L is an effective therapy for neuroblastoma

GSE281811 Homo sapiens (human) Expression microarray 16 samples Submitted 2024/11/13 Platform GPL13667
At a glance

Expression microarray · human · 16 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
16 samples
Data you can get
A processed expression table (series matrix) and the array files, from NCBI.
Summary (written by the submitters)
The child cancer, neuroblastoma (NB), is characterised by a low incidence of mutations and strong oncogenic embryonal driver signals. Many new targeted epigenetic modifier drugs have failed in human trials as monotherapy. We performed a high‐throughput, combination chromatin‐modifier drug screen against NB cells. We screened 13 drug candidates in 78 unique combinations.
Read the full summary ↓
We found that the combination of two histone methyltransferase (HMT) inhibitors: GSK343, targeting EZH2, and SGC0946, targeting DOT1L, demonstrated the strongest synergy across 8 NB cell lines, with low normal fibroblast toxicity. High mRNA expression of both EZH2 and DOT1L in NB tumour samples correlated with the poorest patient survival. Combination HMT inhibitor treatment caused activation of ATF4‐mediated endoplasmic reticulum (ER) stress responses. In addition, glutathione and several amino acids were depleted by HMT inhibitor combination on mass spectrometry analysis. The combination of SGC0946 and GSK343 reduced tumour growth in comparison to single agents. Our results support further investigation of HMT inhibitor combinations as a therapeutic approach in NB.
This dataset
Open GSE281811 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 (GSE281811_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 PRJNA1185740. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39501501) ↗
Samples in this study

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