GEO series

Targeting CIC::DUX4 sarcoma with Minnelide in a dual recombinase-initiated genetically engineered mouse model [dFLEx_BulkRNAseq]

GSE328406 Mus musculus (mouse) RNA-seq (gene expression) 10 samples Submitted 2026/05/20 Platform GPL21103

At a glance

RNA-seq (gene expression) · mouse · 10 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: Mus musculus (mouse)
Samples: 10 samples: 5 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.

Summary (written by the submitters)

CIC::DUX4 sarcoma (CDS) is a lethal cancer driven by a fusion between tumor suppressor Capicua (CIC) and pioneer transcription factor double homeobox 4 (DUX4). To develop an immunocompetent pre-clinical model of CDS, we previously generated three genetically engineered mouse models (GEMMs) of CDS with CIC::DUX4 regulated by loxP-STOP-loxP cassettes.

Read the full summary ↓

However, all three models developed spontaneous tumors without Cre recombinase. Here, we established an innovative GEMM of CDS (dFLEx CDS) that employs a dual recombinase (Cre + FLPE) FLEx-switch design to activate CIC::DUX4 expression and initiate sarcomagenesis in a spatially and temporally-controlled manner. Because CIC::DUX4 drives sarcoma development by activating a distinct oncogenic transcriptional program, we performed a drug screen on human-derived CDS cell lines using a library of compounds that modulate transcriptional regulation. This screen identified Minnelide, an inhibitor of RNA polymerase II-mediated transcription, as a selective inhibitor of CDS. Mechanistically, Minnelide acted through xeroderma pigmentosum type B to alter phosphorylation of RPB1, the largest subunit of RNA polymerase II. Subsequently, RPB1 underwent degradation leading to apoptosis of CDS cells. Minnelide demonstrated in vivo efficacy in autochthonous dFLEx CDS GEMMs and in human CDS xenografts. As Minnelide has already been demonstrated to be safe in clinical trials with activity for adult cancers, these findings nominate Minnelide as a novel therapeutic option to test in CDS patients.

This dataset

Open GSE328406 in finder → Find more mouse RNA-seq 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 GSE328406_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 PRJNA1454915 and SRA study SRP692777. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

5 conditions, mostly in duplicate

170019-dFLExTumor ×2 170024-dFLExTumor ×2 170025-dFLExTumor ×2 3800-KPTumor ×2 3802-KPTumor ×2

Supports a between-group comparison across 10 samples.

How we read this: 5 replicated groups read from 10 sample titles; they account for 10 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

GSM9682362 170019-dFLExTumor-R1 170019-dFLExTumor
GSM9682363 170019-dFLExTumor-R2 170019-dFLExTumor
GSM9682364 170024-dFLExTumor-R1 170024-dFLExTumor
GSM9682365 170024-dFLExTumor-R2 170024-dFLExTumor
GSM9682366 170025-dFLExTumor-R1 170025-dFLExTumor
GSM9682367 170025-dFLExTumor-R2 170025-dFLExTumor
GSM9682368 3800-KPTumor-R1 3800-KPTumor
GSM9682369 3800-KPTumor-R2 3800-KPTumor
GSM9682370 3802-KPTumor-R1 3802-KPTumor
GSM9682371 3802-KPTumor-R2 3802-KPTumor

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