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Transcriptional Rewiring of BET Inhibitor Treated Ewing Sarcoma Cells Augments their Dependency on Focal Adhesion Kinase

GSE299432 Homo sapiens (human) RNA-seq (gene expression) 30 samples Submitted 2025/09/19 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 30 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
Ewing sarcomaThis series is part of our curated briefing on it.
Samples
30 samples: 10 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Epigenetic dysregulation is a hallmark of cancer. Small molecule inhibitors such as bromodomain and extraterminal (BET) protein inhibitors developed to target epigenetic dependencies have demonstrated significant promise in preclinical models. However, clinical success with epigenetic drugs as single agents has been limited by emergence of tumor cell tolerance and escape, which often occurs due to transcriptional rewiring.
Read the full summary ↓
Ewing sarcoma (EwS), a bone and soft tissue tumor driven by the EWS::FLI1 fusion oncoprotein, is characterized by profound oncogene-dependent enhancer reprogramming. Thus, epigenetic modifying therapies are of high therapeutic interest. In this study, we sought to elucidate how EwS cells escape BET inhibition to identify biologically informed drug combinations that could be advanced to clinical trials. As expected, EwS cells and xenografts initially responded to BMS-986158, a pharmaceutical grade BET inhibitor, but proliferation was rapidly restored. A kinase inhibitor screen showed that BMS-986158 drug tolerant persister (DTP) cells were sensitive to inhibitors of Focal Adhesion Kinase (FAK), a critical signaling node downstream of extracellular matrix (ECM) engagement. RNA sequencing revealed that DTP cells had been transcriptionally rewired and that mesenchymal signature and ECM remodeling genes were specifically upregulated. Combining BMS-986158 with the FAK inhibitor Defactinib had synergistic effects on EwS cell proliferation, survival, and invasion in vitro, and significantly inhibited tumor outgrowth in vivo. Our studies identify BET and FAK inhibition as a rational combination therapy worthy of further investigation for EwS, and demonstrate that defining emergent mechanisms of epigenetic drug tolerance can identify new vulnerabilities that can be therapeutically targeted.
This dataset
Open GSE299432 in finder → Find more human RNA-seq datasets → Ewing sarcoma landscape →
Download · which file do I need?

Direct links to NCBI and ENA, 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, or the whole study as GSE299432_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1274418 and SRA study SRP591051. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
10 conditions, mostly in triplicate
CHLA10_3days_BETi ×3 CHLA10_3days_DMSO ×3 CHLA10_20days_BETi ×3 CHLA10_20days_DMSO ×3 A673_3days_BETi ×3 A673_3days_DMSO ×3 A673_20days_BETi ×3 A673_20days_DMSO ×3 +2 more

Supports a between-group comparison across 30 samples.

How we read this: 10 replicated groups read from 30 sample titles; they account for 30 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
More Ewing sarcoma datasets

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