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G-quadruplex stabilizer CX-5461 effectively combines with ionizing radiation to selectively target ATRX-deficient malignant glioma [RNA-seq]

GSE261563 Homo sapiens (human) RNA-seq (gene expression) 30 samples Submitted 2024/03/18 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 30 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
30 samples: 10 conditions, mostly in triplicateGroups 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
G-quadruplex stabilizer CX-5461 effectively combines with radiotherapy to target α-thalassemia/mental retardation X-linked-deficient malignant gliomaNeuro-oncology · 2025
Summary (written by the submitters)
Mutational inactivation of α-thalassaemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of adult and pediatric malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures at GC-rich regions of the genome, altering chromatin accessibility and enhancing DNA damage.
Read the full summary ↓
Building on earlier work, we sought to assess the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in preclinical models of ATRX-deficient glioma. Deploying the G4 stabilizer CX-5461 in patient-derived glioma stem cells (GSCs) in vitro and in GSC murine flank and intracranial xenografts in vivo, we evaluated efficacy as both a single agent and in combination with ionizing radiation (IR), a central element of current treatment standards. CX-5461 promoted dose-sensitive lethality in ATRX-deficient GSCs relative to ATRX-intact controls. Mechanistic studies revealed that CX-5461 disrupted histone variant H3.3 deposition, enhanced replication stress and DNA damage pathways, activated p53-independent apoptosis, and induced G2/M arrest selectively in ATRX-deficient GSCs. These data were corroborated in vivo, where we notably demonstrated that combinational treatment leads to profound tumor growth delay and prolonged survival exclusively in ATRX-deficient flank tumors. In its totality, our work substantively demonstrates efficacy and defines mechanisms of action for a novel therapeutic strategy targeting ATRX-deficient malignant glioma, laying the groundwork for clinical translation.
Published in
G-quadruplex stabilizer CX-5461 effectively combines with radiotherapy to target α-thalassemia/mental retardation X-linked-deficient malignant glioma
Dharmaiah S, Malgulwar PB, Johnson WE et al. · Neuro-oncology 2025 · PMID 39570009 · doi:10.1093/neuonc/noae248
This dataset
Open GSE261563 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 GSE261563_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 PRJNA1087450 and SRA study SRP495122. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39570009) ↗
Study design
10 conditions, mostly in triplicate
SH590_VEH ×3 SH590_CX ×3 543_VEH ×3 543_CX ×3 603_VEH ×3 603_CX ×3 522_VEH ×3 522_CX ×3 +2 more

Supports a between-group comparison across 30 samples.

How we read this: 10 replicated groups read from 30 sample titles; they account for 30 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
Datasets on a similar topic

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