GEO series

Intragenic Epigenetic Deregulation by IDH2 Mutations Synergizes with SRSF2 Mutations Causing Mis-splicing of Key Transcriptional Regulators [RNA-seq]

GSE280581 Homo sapiens (human) RNA-seq (gene expression) 20 samples Submitted 2025/11/26 Platform GPL16791

At a glance

RNA-seq (gene expression) · human · 20 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: 20 samples: 20 samples, each with a distinct title — no replicated groupsGroups 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: Synergistic intragenic epigenetic deregulation by IDH2 and SRSF2 mutations causes mis-splicing of key transcriptional regulatorsScience advances · 2026

Summary (written by the submitters)

Genes impacting DNA methylation (DNAme), like IDH2, are frequently co-mutated with splicing factors, like SRSF2, in acute myeloid leukemia (AML). These co-occurring mutations are associated with more aggressive phenotypes but the underlying molecular mechanisms remain elusive. To address this gap, we profiled wild-type, IDH2R140Q or SRSF2P95 single-mutants and IDH2R140Q/SRSF2P95 double-mutant AMLs at a deep resolution level.

Read the full summary ↓

We find a unique set of mis-spliced genes and differentially methylated CpGs in double-mutants. Mis-spliced exons are enriched in CCNG splicing enhancers and in the corresponding DNAme changes. Using a machine-learning model, we can accurately predict exon inclusion levels from proximal CpGs. These CpGs are more likely to overlap with footprints of RNA-binding and chromatin-modifying complexes but not transcription factors. We also report unique gene expression profiles associated with each genotype; however, the differentially expressed genes do not overlap with mis-spliced transcripts. Instead, the mis-spliced genes encode for proteins that interact with the gene regulatory complexes that control the expression of these differentially expressed genes. Thus, we propose a mechanism where synergism between aberrant DNAme and splicing leads to the mis-splicing of key components in gene regulatory complexes, thus resulting in the aberrant gene expression profiles characteristic of these AMLs.

Published in

Synergistic intragenic epigenetic deregulation by IDH2 and SRSF2 mutations causes mis-splicing of key transcriptional regulators

Telonis AG, Stanley RF, Adelman ER et al. · Science advances 2026 · PMID 41481703 · doi:10.1126/sciadv.adu8292

This dataset

Open GSE280581 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 GSE280581_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 PRJNA1179445 and SRA study SRP541817. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41481703) ↗

Study design

20 samples, each with a distinct title — no replicated groups

Supports a case/control comparison: 11 samples read as cases, 3 as controls.

How we read this: Read from 20 sample titles: 20 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

GSM8601579 201T1B_IDH2-Mutant_SRSF2-WT RNA
GSM8601580 225T15B_IDH2-WT_SRSF2-Mutant RNA
GSM8601581 246T9B_IDH2-Mutant_SRSF2-WT RNA
GSM8601582 247T2Ba_IDH2-Mutant_SRSF2-Mutant RNA
GSM8601583 247T2Bb_IDH2-Mutant_SRSF2-Mutant RNA
GSM8601584 283T9B_IDH2-Mutant_SRSF2-Mutant RNA
GSM8601585 287T1M_IDH2-WT_SRSF2-Mutant RNA
GSM8601586 475T1B_IDH2-WT_SRSF2-Mutant RNA
GSM8601587 495T1M_IDH2-Mutant_SRSF2-Mutant RNA
GSM8601588 523T2B_IDH2-Mutant_SRSF2-Mutant RNA
GSM8601589 543T6B_IDH2-Mutant_SRSF2-WT RNA
GSM8601590 54T1B_IDH2-WT_SRSF2-WT RNA
GSM8601591 556T2B_IDH2-Mutant_SRSF2-Mutant RNA
GSM8601592 560T3B_IDH2-WT_SRSF2-Mutant RNA
GSM8601593 584T3M_IDH2-WT_SRSF2-Mutant RNA
GSM8601594 587T2B_IDH2-WT_SRSF2-WT RNA
GSM8601595 614T1M_IDH2-Mutant_SRSF2-Mutant RNA
GSM8601596 648T1B_IDH2-Mutant_SRSF2-WT RNA
GSM8601597 736T3b_IDH2-WT_SRSF2-Mutant RNA
GSM8601598 85T1M_IDH2-WT_SRSF2-WT RNA

Datasets on a similar topic

GSE263299 Mis-splicing of mitotic regulators sensitizes SF3B1-mutated human HSCs to CHK1 inhibition [RNA-seq] 10 samples shares mis-splicing, regulators
GSE305480 Disease specific epigenetic deregulation of enhancers, transposons and polycomb targets in acute promyelocytic leukemia 6 samples shares deregulation, epigenetic
GSE263300 Mis-splicing of mitotic regulators sensitizes SF3B1-mutated human HSCs to CHK1 inhibition [scRNA-seq] 2 samples shares mis-splicing, regulators
GSE213002 ATR/CHK1/WEE1 dependency in SRSF2-mutated myeloid malignancies 16 samples shares srsf2
GSE299161 MALNC: A new mutant NPM1/IDH2R140 and PML-RARA-associated lncRNA with impact on AML cell proliferation, maturation and drug response 15 samples shares idh2
GSE261434 A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma [RNAseq_Enasidenib_L2975_SW1353] 12 samples shares idh2
GSE242063 Effect on gene expression of knock down of Scrambled control or Kdm3b on wild-type or Idh2 R140Q TF-1 cells 9 samples shares idh2
GSE300406 Effect of knock-down SRSF2 6 samples shares srsf2

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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.