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PAX3-FOXO1 drives targetable cell state-dependent metabolic vulnerabilities in rhabdomyosarcoma

GSE286950 Homo sapiens (human) RNA-seq (gene expression) 16 samples Submitted 2025/09/02 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 16 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
Soft tissue sarcomaThis series is part of our curated briefing on it.
Samples
16 samples: 8 conditions, mostly in duplicateGroups 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
PAX3-FOXO1 Drives Targetable Cell State-Dependent Metabolic Vulnerabilities in RhabdomyosarcomaCancer research · 2025
Summary (written by the submitters)
PAX3-FOXO1, an oncogenic transcription factor, drives a particularly aggressive subtype of rhabdomyosarcoma (RMS) by enforcing gene expression programs that support malignant cell states. In this study, we show that PAX3-FOXO1+ RMS cells exhibit altered pyrimidine metabolism and increased dependence on enzymes involved in de novo pyrimidine synthesis, including dihydrofolate reductase (DHFR).
Read the full summary ↓
Consequently, PAX3-FOXO1+ cells display increased sensitivity to inhibition of DHFR by the chemotherapeutic drug methotrexate, and this dependence is rescued by provision of pyrimidine nucleotides. Methotrexate treatment mimics the metabolic and transcriptional impact of PAX3-FOXO1 silencing, reducing expression of genes related to PAX3-FOXO1-driven malignant cell states. Accordingly, methotrexate treatment slows the growth of multiple PAX3-FOXO1+ tumor xenograft models but not their fusion-negative counterparts. Taken together, these data demonstrate that PAX3-FOXO1 induces cell states characterized by altered pyrimidine dependence and nominates methotrexate as an addition to the current therapeutic arsenal for treatment of these malignant pediatric tumors.
Published in
PAX3-FOXO1 Drives Targetable Cell State-Dependent Metabolic Vulnerabilities in Rhabdomyosarcoma
Paras KI, Brunner JS, Montero AM et al. · Cancer research 2025 · PMID 40911784 · doi:10.1158/0008-5472.CAN-25-0315
This dataset
Open GSE286950 in finder → Find more human RNA-seq datasets → Soft tissue 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 GSE286950_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 PRJNA1210602 and SRA study SRP557274. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40911784) ↗
Study design
8 conditions, mostly in duplicate
RH30, vehicle (DMSO, 48 h), ×2 RH30, MTX (48 h), ×2 RH41, vehicle (DMSO, 48 h), ×2 RH41, MTX (48 h), ×2 RD, vehicle (DMSO, 48 h), ×2 RD, MTX (48 h), ×2 SMS-CTR, vehicle (DMSO, 48 h), ×2 SMS-CTR, MTX (48 h), ×2

Supports a between-group comparison across 16 samples.

How we read this: 8 replicated groups read from 16 sample titles; they account for 16 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 Soft tissue sarcoma datasets

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