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DNA Hypomethylation is Not Cell Intrinsically Toxic to Polycomb Repressive Complex 2 Deficient Malignant Peripheral Nerve Sheath Tumors

GSE305426 Homo sapiens (human) DNA methylation 36 samples Submitted 2026/08/05 Platform GPL34284
At a glance

DNA methylation · human · 36 samples

What it is
DNA methylationChemical marks on DNA that help switch genes on or off.
Organism
Homo sapiens (human)
Topic
Soft tissue sarcomaThis series is part of our curated briefing on it.
Samples
36 samples: 18 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.
Summary (written by the submitters)
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas and the most common cause of disease-associated death for Neurofibromatosis Type 1 (NF1) patients. In the context of NF1, MPNSTs develop from benign premalignant precursors. In the majority of cases, the transition to malignancy is accompanied by loss of the Polycomb repressive complex 2 (PRC2), which results in aberrant upregulation of over 1200 genes due to global depletion of histone H3 lysine 27 trimethylation (H3K27me3).
Read the full summary ↓
Studies have suggested that cells compensate for the loss of this repressive histone mark by increasing DNA methylation throughout the genome. This study used a Nanopore-based genome skimming method to analyze genome-wide DNA methylation and the transcriptome in MPNST cell lines and isogenic PRC2-deficient and -proficient CRISPR-engineered immortalized human Schwann cells. In addition to effects of PRC2 status, we also measured the effects of two DNA methyltransferase inhibitors (DNMTi), decitabine and azacitidine. We found that PRC2 status does not affect global DNA methylation state and that decitabine and azacitidine have differential effects on MPNSTs. While both DNMTis greatly decrease global DNA methylation, they upregulate different targets. Azacitidine upregulates genes involved in RNA processing pathways and can kill MPNST cells directly, while decitabine upregulates genes involved in the immune response and is only able to reduce tumor growth via indirect effects on the tumor microenvironment in vivo. We show that DNA hypomethylation alone is insufficient to kill MPNST cells, regardless of PRC2 status. However, DNMTi could be useful in combination with other therapies for MPNST patients.
This dataset
Open GSE305426 in finder → Find more human 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 GSE305426_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: Look for beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1305719 and SRA study SRP608856. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
18 conditions, mostly in duplicate
JH-2-002-CL-AZA ×2 JH-2-002-CL-DAC ×2 JH-2-002-CL-DMSO ×2 ST88-14-AZA ×2 ST88-14-DAC ×2 ST88-14-DMSO ×2 STS26T-AZA ×2 STS26T-DAC ×2 +10 more

Supports a between-group comparison across 36 samples.

How we read this: 18 replicated groups read from 36 sample titles; they account for 36 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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