GEO series

Pre-clinical spheroid models identify BMX as a therapeutic target for metastatic MYCN non-amplified neuroblastoma (RNA-Seq)

GSE223900 Homo sapiens (human) RNA-seq (gene expression) 14 samples Submitted 2024/06/30 Platform GPL16791

At a glance

RNA-seq (gene expression) · human · 14 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: 14 samples
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: Preclinical spheroid models identify BMX as a therapeutic target for metastatic MYCN nonamplified neuroblastomaJCI insight · 2024

Summary (written by the submitters)

The development of targeted therapies has provided new hope for an increasing number of cancer patients affected by previously incurable diseases. The clinical success of this approach, however, is limited by numerous challenges, including a better control of cell plasticity, particularly in refractory and metastatic patients. Here we addressed this question in Neuroblastoma (NB), an aggressive pediatric malignancy, which remains a clinical challenge for high-risk patients.

Read the full summary ↓

NB originates from neural crest-derived progenitors through defective differentiation programs combined with oncogenic activity due to genetic and epigenetic alterations. In order to identify critical genes responsible for tumor aggressiveness we performed combined chromatin and transcriptome analyses on matched primary xenografts, spheroids and differentiated adherent cultures, which we derived from metastatic non-MYCN amplified (nMNA) NB patients. Our approach identified the kinase BMX among the most differentially regulated genes between patient-derived xenografts and spheroids versus adherent models. We further found that BMX expression is associated with high tumor stage and poor patient survival in multiple NB transcriptomic datasets and critical to maintain the self-renewal and tumorigenic potential of NB spheroids. Moreover, we uncovered a positive correlation between BMX expression and the mesenchymal tumor cell phenotype, which was previously associated with increased chemo-resistance. Finally, we show that BMX inhibitors can readily reverse this cellular state, increase the sensitivity of NB spheroids toward standard of care chemotherapy, and reduce tumor growth in preclinical NB models. Altogether, our study identifies BMX as a novel promising therapeutic target for high-risk patients with relapsed or refractory nMNA NB tumors.

Published in

Preclinical spheroid models identify BMX as a therapeutic target for metastatic MYCN nonamplified neuroblastoma

Sundaramoorthy S, Colombo DF, Sanalkumar R et al. · JCI insight 2024 · PMID 39133652 · doi:10.1172/jci.insight.169647

This dataset

Open GSE223900 in finder → Find more human 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 GSE223900_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 PRJNA928777. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39133652) ↗

Samples in this study

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+ 14 more — browse all 14 samples with per-sample file links →

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GSE294308 5-hydroxymethylcytosine deposition mediates Polycomb Repressive Complex 2 function in MYCN-amplified neuroblastoma [RNA-seq] 14 samples shares mycn, neuroblastoma
GSE164456 Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma 69 samples shares mycn, neuroblastoma
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GSE211953 The SAGA complex maintains the oncogenic gene expression program in MYCN-amplified neuroblastoma [ChIP-Seq] 35 samples shares mycn, neuroblastoma
GSE294307 5-hydroxymethylcytosine deposition mediates Polycomb Repressive Complex 2 function in MYCN-amplified neuroblastoma [CUT&Run] 18 samples shares mycn, neuroblastoma

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