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Co-targeting CDK2 and CDK9 inhibits MYC oncogenic programs and has anti-tumor effects in CIC-rearranged sarcoma

GSE291596 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/03/10 Platform GPL15433
At a glance

RNA-seq (gene expression) · human · 12 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)
Samples
12 samples: 3 × CIC01-DMSO vs 3 × CIC01-Tagtociclib 200nM vs 3 × CIC02-DMSO vs 3 × CIC02-Tagtociclib 200nMGroups 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-rearranged sarcoma is an aggressive mesenchymal neoplasm characterized by capicua (CIC) gene rearrangement and molecular dependence on the CDK2-cyclin E complex. Given its high metastatic potential and poor clinical outcomes, there is an urgent need to identify biologic vulnerabilities for therapeutic targeting. Here, we determined the efficacy of CDK2-targeted therapies in preclinical models of CIC- rearranged sarcoma including two new cell lines and xenografts driven by CIC::DUX4 and CIC::NUTM1 fusion, respectively.
Read the full summary ↓
Functional analyses revealed that CIC- rearranged sarcomas are MYC-driven cancers and can be targeted with the selective CDK2 inhibitor tagtociclib (PF-07104091) in vitro and in vivo. Concomitant with RB1- mediated proliferative arrest, tagtociclib inhibited MYC oncogenic programs. Moreover, combination of tagtociclib with the CDK9 inhibitors KB-0742 or AZD4573 was synergistic and enhanced apoptotic cell death in vitro and in vivo. These results demonstrate anti-tumor effects of concurrent inhibition of CDK2 and CDK9 through MYC transcriptional repression and provide a strong rationale for clinical evaluation of CDK2 and CDK9-targeted combination therapies in patients with CIC-rearranged sarcoma.
This dataset
Open GSE291596 in finder → Find more human 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 GSE291596_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 PRJNA1234207 and SRA study SRP569343. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × CIC01-DMSO vs 3 × CIC01-Tagtociclib 200nM vs 3 × CIC02-DMSO vs 3 × CIC02-Tagtociclib 200nM

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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
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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.