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Hydroxychloroquine prevents resistance and potentiates antitumor effect of SHP2 inhibition in NF1-associated Malignant Peripheral Nerve Sheath Tumors

GSE283902 Mus musculus (mouse) RNA-seq (gene expression) 31 samples Submitted 2024/12/12 Platform GPL24676Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 31 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)
Topic
Soft tissue sarcomaThis series is part of our curated briefing on it.
Samples
31 samples: 7 conditions, mostly with about 4 replicates eachGroups 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
Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumorsProceedings of the National Academy of Sciences of the United States of America · 2025
Summary (written by the submitters)
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within pre-existing benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic NF1 loss eliciting RAS pathway activation and respond favorably to MEK inhibitor therapy.
Read the full summary ↓
MPNSTs harbor additional mutations and respond poorly to MEK inhibition. Our analysis of genetically engineered and orthotopic patient-derived xenograft MPNST tumor models indicates that MEK inhibition has poor anti-tumor efficacy. By contrast, upstream inhibition of RAS through the protein-tyrosine phosphatase SHP2 reduced downstream signaling and suppressed NF1 MPNST growth, although resistance eventually emerged. To investigate possible mechanisms of acquired resistance, kinomic analyses of resistant tumors was performed, and data analysis identified enrichment of activated autophagy pathway protein kinases. Combining SHP2 inhibition with hydroxychloroquine resulted in durable responses in NF1 MPNSTs in both genetic and orthotopic xenograft mouse models. Our studies could be rapidly translated into a clinical trial to evaluate SHP2 inhibition in conjunction with hydroxychloroquine as a novel treatment approach for NF1 MPNSTs.
Published in
Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors
Sait SF, Tang KH, Angus SP et al. · Proceedings of the National Academy of Sciences of the United States of America 2025 · PMID 39793045 · doi:10.1073/pnas.2407745121
This dataset
Open GSE283902 in finder → Find more RNA-seq datasets → Soft tissue sarcoma landscape →
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 GSE283902_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 PRJNA1195991 and SRA study SRP550320. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39793045) ↗
Study design
7 conditions, mostly with about 4 replicates each
S ×6 Shp-21-Day ×6 PDX16-V ×4 PDX16-S ×4 VEH-5-Day ×4 Shp-5-Day ×4 V ×3

Supports a between-group comparison across 31 samples.

How we read this: 7 replicated groups read from 31 sample titles; they account for 31 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
More Soft tissue sarcoma datasets

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