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MYBL2 drives prostate cancer plasticity and identifies CDK2 as a therapeutic vulnerability in RB1-loss and neuroendocrine prostate cancer [ATAC-seq]

GSE271327 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 3 samples Submitted 2024/07/30 Platform GPL19057
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 3 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
Mus musculus (mouse)
Samples
3 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
MYBL2 Drives Prostate Cancer Plasticity: Inhibiting Its Transcriptional Target CDK2 for RB1-Deficient Neuroendocrine Prostate CancerCancer research communications · 2024
Summary (written by the submitters)
Phenotypic plasticity is a recognized mechanism driving therapeutic resistance in prostate cancer (PCa) patients. While underlying molecular causations driving phenotypic plasticity have been identified, therapeutic success is yet to be achieved. To identify putative master regulator transcription factors (MR-TF) driving phenotypic plasticity in PCa, this work utilized a multiomic approach using genetically engineered mouse models of prostate cancer combined with patient data to identify MYBL2 as a significantly enriched transcription factor in PCa exhibiting phenotypic plasticity.
Read the full summary ↓
Genetic inhibition of Mybl2 using independent murine PCa cell lines representing phenotypic plasticity demonstrated Mybl2 loss significantly decreased in vivo growth as well as cell fitness and repressed gene expression signatures involved in pluripotency and stemness. Because MYBL2 is currently not druggable, a MYBL2 gene signature was employed to identify cyclin-dependent kinase-2 (CDK2) as a potential therapeutic target. CDK2 inhibition phenocopied genetic loss of Mybl2 and significantly decreased in vivo tumor growth associated with enrichment of DNA damage. Together, this work demonstrates MYBL2 as an important MR-TF driving phenotypic plasticity in PCa. Further, high MYBL2 activity identifies PCa that would be responsive to CDK2 inhibition.
Published in
MYBL2 Drives Prostate Cancer Plasticity: Inhibiting Its Transcriptional Target CDK2 for RB1-Deficient Neuroendocrine Prostate Cancer
German B, Alaiwi SA, Ho KL et al. · Cancer research communications 2024 · PMID 39113611 · doi:10.1158/2767-9764.CRC-24-0069
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 GSE271327_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 PRJNA1130940 and SRA study SRP517604. Searching any of these in the dataset finder brings you back here.

Samples in this study

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+ 3 more — browse all 3 samples with per-sample file links →

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