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CDK12 as an entry point for combination therapy in high-risk neuroblastoma [RNA-seq]

GSE287496 Homo sapiens (human) RNA-seq (gene expression) 59 samples Submitted 2026/07/29 Platform GPL24676Platform GPL30173
At a glance

RNA-seq (gene expression) · human · 59 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)
Topic
NeuroblastomaThis series is part of our curated briefing on it.
Samples
59 samples: 17 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.
Summary (written by the submitters)
High-risk neuroblastoma (HR-NB) patients undergo aggressive treatments, yet more than half succumb to the disease. HR-NB cells are marked by chronic replicative stress, partly driven by MYCN amplification, and targeting DNA damage response (DDR) pathways presents a promising therapeutic approach. BRCA1 and CDK12, located on the recurrently gained 17q region in HR-NB, play essential roles in maintaining genomic stability.
Read the full summary ↓
In this study, we hypothesized that pharmacological inactivation of CDK12 could induce a BRCAness phenotype, making NB cells vulnerable to synthetic lethal targets. We evaluated the efficacy of CDK12 inhibitors and protein degraders in a panel of NB cell lines and organoids. Molecular effects of CDK12 inactivation were investigated through immunoblotting and RNA-sequencing. A high-throughput compound screen combining CDK12-targeting agents with a library of ~200 drugs revealed that single-agent treatment with CDK12 inhibitors or degraders induced significant NB cell death in vitro. This was accompanied by a BRCAness signature, including decreased BRCA1 and RAD51 levels, increased DNA damage, and downregulation of DNA repair genes. Additionally, we observed upregulation of immune pathways, suggesting potential for enhancing immunogenicity in HR-NB. The combinatorial drug screen revealed strong synergy with DNA-damaging agents, PARP inhibitors, Ras/MAPK inhibitors, and other compounds. These findings confirm CDK12 as a novel therapeutic target, and the induction of a BRCAness phenotype provides a basis for combination treatments.
This dataset
Open GSE287496 in finder → Find more human RNA-seq datasets → Neuroblastoma 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 GSE287496_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 PRJNA1213098 and SRA study SRP558527. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
17 conditions, mostly in triplicate
N206_MER_OKI_DMSO ×4 N206_Mer_single ×4 N206_OKI_GI50 ×4 N206_OKI_Mer_Combo ×4 N206_OKI_single ×4 N206_BSJ ×4 SH-SY5Y_BSJ ×4 SH-SY5Y_BSJ_DMSO ×4 +9 more

Supports a between-group comparison across 59 samples.

How we read this: 17 replicated groups read from 59 sample titles; they account for 59 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

+ 19 more — browse all 59 samples with per-sample file links →

More Neuroblastoma datasets

Search all human RNA-seq datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.