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Eradicating neuroblastomas by an RBM39 degrader in combination with anti-GD2 immunotherapy regardless of cancer cell state alterations [CUT&Tag]

GSE251915 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 10 samples Submitted 2025/06/05 Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 10 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Samples
10 samples: 2 × SKNAS-Naive-H3K27ac vs 2 × SKNAS-IR1-H3K27ac vs 2 × SKNAS-IR2-H3K27ac vs 2 × NB14-ctrl1-H3K27acGroups 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
RBM39 degrader invigorates natural killer cells to eradicate neuroblastoma despite cancer cell plasticitybioRxiv : the preprint server for biology · 2024
Summary (written by the submitters)
The lineage plasticity of neuroblastoma cells is defined by a mixture of two major cell states, adrenergic (ADRN) and mesenchymal (MES), which presumably contributes to therapy resistance. However, how the neuroblastoma cells switch their cell states during therapy remains largely unknown and how to eradicate neuroblastoma cells regardless of their cell state alterations is a clinical challenge.
Read the full summary ↓
By using four distinct human and murine neuroblastoma models treated with indisulam, a molecular glue drug serving as a selective RBM39 degrader, we show that cancer cells not only can undergo bidirectional switch of ADRN and MES cell states, but also can acquire additional cell states of melanoma and Schwann cell progenitors, reminiscent of the cellular pliancy of neural crest cells. The lineage alterations of neuroblastoma cells are coupled with epigenetic changes and dependency switch of lineage-specific transcription factors. Nevertheless, indisulam treatment induces an inflamed tumor microenvironment leading to an immune cell infiltration. The combination of indisulam with anti-GD2 monoclonal immunotherapy results in a durable complete response in transgenic neuroblastoma models driven by MYCN and ALK mutant oncogenes, providing a therapeutic rationale to eradicate tumor cells even when they acquire alternative cell lineage(s) in response to treatment.
Published in
RBM39 degrader invigorates natural killer cells to eradicate neuroblastoma despite cancer cell plasticity
Singh S, Fang J, Jin H et al. · bioRxiv : the preprint server for biology 2024 · PMID 38585889 · doi:10.1101/2024.03.21.586157
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 GSE251915_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1055922 and SRA study SRP479658. Searching any of these in the dataset finder brings you back here.

Study design
2 × SKNAS-Naive-H3K27ac vs 2 × SKNAS-IR1-H3K27ac vs 2 × SKNAS-IR2-H3K27ac vs 2 × NB14-ctrl1-H3K27ac

Supports a between-group comparison across 8 samples.

How we read this: 4 replicated groups read from 10 sample titles; they account for 8 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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