GEO series

EWS-WT1 fusion isoforms establish oncogenic programs and therapeutic vulnerabilities in Desmoplastic Small Round Cell Tumors.

GSE248842 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 12 samples Submitted 2024/10/01 Platform GPL18573

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 12 samples

What it is: ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism: Homo sapiens (human)
Samples: 12 samples: 10 distinct titles, 2 of them repeatedGroups 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.
Paper: EWS-WT1 fusion isoforms establish oncogenic programs and therapeutic vulnerabilities in desmoplastic small round cell tumorsNature communications · 2024

Summary (written by the submitters)

EWS fusion oncoproteins underlie the pathogenesis of several human malignancies including Desmoplastic Small Round Cell Tumor (DSRCT), an aggressive mesenchymal tumor driven by fusions between the disordered domain of EWS and the developmental transcription factor WT1. Here we combined chromatin occupancy and long-range interaction profiles to identify EWS-WT1-dependent gene regulation networks and directly controlled target genes.

Read the full summary ↓

We show that EWS-WT1 operates primarily as a powerful activator of distal regulatory elements and controls an oncogenic gene expression program that characterize primary DSRCTs. Moreover, EWS-WT1 has two isoforms that differ by three amino acids in their DNA binding domain (+/- KTS), as observed for wild type WT1, and we show that each fusion isoform has a specific DNA binding profile that is distinct from its wild type counterparts and requires a functional EWSR1 prion like domain. Remarkably, xenograft experiments using human mesothelial cells, candidate cells of origin of DSRCT, reveal that both isoforms are required to generate viable tumors that resemble DSRCT. Finally, we identify new candidate EWS-WT1 target genes with potential therapeutic implications, including CCND1, whose inhibition by the clinically-approved drug Palbociclib leads to marked tumor burden decrease in DSRCT PDXs in vivo. Taken together, our studies identify gene regulation programs and therapeutic vulnerabilities in DSRCT and provide a mechanistic understanding of the complex isoform-dependent oncogenic activity of EWS-WT1.

Published in

EWS-WT1 fusion isoforms establish oncogenic programs and therapeutic vulnerabilities in desmoplastic small round cell tumors

Boulay G, Broye LC, Dong R et al. · Nature communications 2024 · PMID 39198430 · doi:10.1038/s41467-024-51851-3

This dataset

Open GSE248842 in finder → Find more human ChIP / ATAC / CUT&Tag datasets →

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 GSE248842_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1046095 and SRA study SRP474667. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39198430) ↗

Study design

10 distinct titles, 2 of them repeated

ChIP DSRCT3.H3K4me ×2 DSRCT4.H3K4me ×2

How we read this: Read from 12 sample titles: 10 distinct titles with little repetition. 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

GSM7921189 ChIP DSRCT3.H3K27ac
GSM7921190 ChIP DSRCT3.H3K27me3
GSM7921191 ChIP DSRCT3.H3K4me1
GSM7921192 ChIP DSRCT3.H3K4me3
GSM7921193 ChIP DSRCT3.H3K9ac
GSM7921194 ChIP DSRCT3.INPUT
GSM8351418 DSRCT4.H3K27ac
GSM8351419 DSRCT4.H3K27me3
GSM8351420 DSRCT4.H3K4me1
GSM8351421 DSRCT4.H3K4me3
GSM8351422 DSRCT4.H3K9ac
GSM8351423 DSRCT4.INPUT

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