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Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor models

GSE276109 Mus musculus (mouse) RNA-seq (gene expression) 22 samples Submitted 2025/04/11 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 22 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
22 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.
Paper
Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor modelsThe Journal of biological chemistry · 2025
Summary (written by the submitters)
Mutations in isocitrate dehydrogenase 1 (IDH1) impart a neomorphic reaction that produces D-2-hydroxyglutarate (D2HG), which can inhibit DNA demethylases to drive tumorigenesis. Mutations affect residue R132 and display distinct catalytic profiles for D2HG production. We show that catalytic efficiency of D2HG production is greater in IDH1 R132Q than R132H mutants, and expression of IDH1 R132Q in cellular and xenograft models leads to higher D2HG concentrations in cells, tumors, and sera compared to R132H.
Read the full summary ↓
Though expression of IDH1 R132Q leads to hypermethylation in DNA damage pathways, DNA hypomethylation is more notable when compared to IDH1 R132H expression. Transcriptome analysis shows increased expression of many pro-tumor pathways upon expression of IDH1 R132Q versus R132H, including transcripts of EGFR and PI3K signaling pathways. Thus, IDH1 mutants appear to modulate D2HG levels via altered catalysis and are associated with distinct epigenetic and transcriptomic consequences, with higher D2HG levels appearing to be associated with more aggressive tumors.
Published in
Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor models
Schwartz AV, Chao G, Robinson M et al. · The Journal of biological chemistry 2025 · PMID 40188944 · doi:10.1016/j.jbc.2025.108477
This dataset
Open GSE276109 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 GSE276109_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 PRJNA1154701 and SRA study SRP529741. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40188944) ↗
Study design
5 conditions, mostly in duplicate
U87MG cells, IDH1 R132Q expression, tumor col… ×5 U87MG cells, IDH1 R132H expression, tumor col… ×4 U87MG cells, IDH1 WT expression, tumor collec… ×3 HT1080 cells (+/-), IDH1 R132Q expression, tu… ×2 HT1080 cells (+/-), IDH1 R132Q expression, tu… ×2 HT1080 cells (+/-), IDH1 R132H expression, tu… ×1 HT1080 cells (+/-), IDH1 R132H expression, tu… ×1 HT1080 cells (+/-), IDH1 R132H expression, tu… ×1 +3 more

Supports a between-group comparison across 16 samples.

How we read this: 5 replicated groups read from 22 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
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