GEO series
Selective inhibition of BRAF and CRAF sensitizes NF1-deficient malignant peripheral nerve sheath tumors to MEK inhibitors
GSE303418
Homo sapiens (human)
RNA-seq (gene expression)
36 samples
Submitted 2025/08/01
Platform GPL24676
At a glance
RNA-seq (gene expression) · human · 36 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
- 36 samples: 11 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
- Selective inhibition of BRAF and CRAF sensitizes NF1-deficient malignant peripheral nerve sheath tumors to MEK inhibitorsMolecular medicine (Cambridge, Mass.) · 2025
Summary (written by the submitters)
Background: Treatment for patients with malignant peripheral nerve sheath tumors (MPNST) is an unmet clinical need. Loss of NF1 in MPNST leads to hyperactivation of RAS oncoproteins, however little is known about relevant downstream oncogenic signaling and effective targeted therapies in MPNST are still lacking.
Read the full summary ↓
Methods: Conditional gene expression, CRISPR-CAS9, and shRNA-mediated knockdown were used to perform gain/loss-of-function experiments to explore the effect of reconstituting the GTPase-activating protein-related domain of NF1 or knockdown of A/B/CRAF kinases on ERK signaling output and MPNST cell growth. Colony formation, cell proliferation and live cells imaging assays were performed to assess cell growth in response to genetic manipulations or drug treatments. Pathway enrichment analysis on RNA sequencing following drug perturbation, efficacy studies in cell-line-derived and patient-derived xenograft models, and immunoblotting/immunohistochemistry were conducted to assess tumor growth and ERK pathway activity in cells or in pharmacodynamic analyses of tumor xenografts. Results: NF1 loss activates RAS/ERK signaling through B/CRAF, and cell growth and ERK signaling of NF1-MPNST are dependent on B/CRAF, but not ARAF. Genetic or pharmacological inhibition of B/CRAF using paralog-selective RAF inhibitor (RAFi) significantly potentiates MEK inhibitor (MEKi) treatment through more effective suppression of ERK signaling and proliferation. This is shown in multiple traditional and patient-derived cell line and xenograft models, including those with acquired resistance to MEKi.
Published in
Wang J, Sarkar A, Garcia N et al.
· Molecular medicine (Cambridge, Mass.) 2025
· PMID 41023593
· doi:10.1186/s10020-025-01353-9
This dataset
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.
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 GSE303418_RAW.tar (it can run to tens of gigabytes).
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.
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 PRJNA1295379 and SRA study SRP603158. Searching any of these in the dataset finder brings you back here.
Study design
11 conditions, mostly in duplicate
S462 cell line, control, ×3
NF90.8 cell line, 250 nM LXH254 48h, ×3
S462 cell line, 250 nM LXH254 + 10 nM trameti… ×3
NF90.8 cell line, 10 nM trametinib 48h, ×3
NF90.8 cell line, control ×2
ST8814 cell line, control, ×2
S462 cell line, 250 nM LXH254 48h, ×2
ST8814 cell line, 250 nM LXH254 48h, ×2
+13 more
Supports a between-group comparison across 26 samples.
How we read this: 11 replicated groups read from 36 sample titles; they account for 26 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
- GSM9126364 NF90.8 cell line, control replicate 1,
- GSM9126365 S462 cell line, control, replicate 1 S462 cell line, control,
- GSM9126366 ST8814 cell line, control, replicate 1,
- GSM9126367 NF90.8 cell line, control replicate 2 NF90.8 cell line, contr…
- GSM9126368 S462 cell line, control, replicate 2 S462 cell line, control,
- GSM9126369 ST8814 cell line, control, replicate 2 ST8814 cell line, contr…
- GSM9126370 NF90.8 cell line, control replicate 3 NF90.8 cell line, contr…
- GSM9126371 S462 cell line, control, replicate 3 S462 cell line, control,
- GSM9126372 ST8814 cell line, control, replicate 3 ST8814 cell line, contr…
- GSM9126373 NF90.8 cell line, 250 nM LXH254 48h, replicate 1 NF90.8 cell line, 250 n…
- GSM9126374 S462 cell line, 250 nM LXH254 48h, replicate 1 S462 cell line, 250 nM …
- GSM9126375 ST8814 cell line, 250 nM LXH254 48h, replicate 1,
- GSM9126376 NF90.8 cell line, 250 nM LXH254 48h, replicate 2 NF90.8 cell line, 250 n…
- GSM9126377 S462 cell line, 250 nM LXH254 48h, replicate 2 S462 cell line, 250 nM …
- GSM9126378 ST8814 cell line, 250 nM LXH254 48h, replicate 2 ST8814 cell line, 250 n…
- GSM9126379 NF90.8 cell line, 250 nM LXH254 48h, replicate 3 NF90.8 cell line, 250 n…
- GSM9126380 S462 cell line, 250 nM LXH254 48h , replicate 3
- GSM9126381 ST8814 cell line, 250 nM LXH254 48h, replicate 3 ST8814 cell line, 250 n…
- GSM9126382 NF90.8 cell line, 250 nM LXH254 + 10nM trametinib 48h, replicate 1 NF90.8 cell line, 250 n…
- GSM9126383 S462 cell line, 250 nM LXH254 + 10 nM trametinib 48h, replicate 1 S462 cell line, 250 nM …
- GSM9126384 ST8814 cell line, 250 nM LXH254 + 10 nM trametinib 48h, replicate 1,
- GSM9126385 NF90.8 cell line, 250 nM LXH254 + 10 nM trametinib 48h, replicate 2
- GSM9126386 S462 cell line, 250 nM LXH254 + 10 nM trametinib 48h, replicate 2 S462 cell line, 250 nM …
- GSM9126387 ST8814 cell line, 250 nM LXH254 + 10 nM trametinib 48h, replicate 2 ST8814 cell line, 250 n…
- GSM9126388 NF90.8 cell line, 250 nM LXH254 + 10nM trametinib 48h, replicate 3 NF90.8 cell line, 250 n…
- GSM9126389 S462 cell line, 250 nM LXH254 + 10 nM trametinib 48h, replicate 3 S462 cell line, 250 nM …
- GSM9126390 ST8814 cell line, 250 nM LXH254 + 10 nM trametinib 48h, replicate 3 ST8814 cell line, 250 n…
- GSM9126391 NF90.8 cell line, 10 nM trametinib 48h, replicate 1 NF90.8 cell line, 10 nM…
- GSM9126392 S462 cell line, 10 nM trametinib 48h, replicate 1 S462 cell line, 10 nM t…
- GSM9126393 ST8814 cell line, 10nM trametinib 48h, replicate 1,
- GSM9126394 NF90.8 cell line, 10 nM trametinib 48h, replicate 2 NF90.8 cell line, 10 nM…
- GSM9126395 S462 cell line, 10nM trametinib 48h, replicate 2
- GSM9126396 ST8814 cell line, 10 nM trametinib 48h, replicate 2
- GSM9126397 NF90.8 cell line, 10 nM trametinib 48h, replicate 3 NF90.8 cell line, 10 nM…
- GSM9126398 S462 cell line, 10 nM trametinib 48h, replicate 3 S462 cell line, 10 nM t…
- GSM9126399 ST8814 cell line, 10nM trametinib 48h, replicate 3
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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.