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Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer

GSE249258 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2024/06/14 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 24 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
24 samples: 12 conditions, mostly in duplicateGroups 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
Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancerCancer cell · 2024
Summary (written by the submitters)
Small cell lung cancers (SCLC) are comprised of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLC, ~12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities for this subtype.
Read the full summary ↓
Here using genome-scale CRISPR/Cas9-based screens reporting on POU2F3 expression in SCLC cell lines, we define mSWI/SNF complexes, including non-canonical BAF complexes (ncBAF), as top regulators of POU2F3 and dependencies specific to the POU2F3-positive subtype. Notably, clinical-grade pharmacologic mSWI/SNF complex inhibition attenuates proliferation of all POU2F3-positive SCLCs, while disruption of ncBAF via BRD9 degradation is uniquely effective in pure non-neuroendocrine POU2F3-SCLCs. mSWI/SNF complexes maintain accessibility over gene loci central to POU2F3-mediated gene regulatory networks. Finally, chemical targeting of SMARCA4/2 mSWI/SNF ATPases and BRD9 decrease POU2F3-SCLC tumor growth and increase survival in vivo. Taken together, these results define mSWI/SNF-mediated global governance of the POU2F3 oncogenic program and suggest mSWI/SNF inhibition as a therapeutic strategy in SCLC.
Published in
Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer
Duplaquet L, So K, Ying AW et al. · Cancer cell 2024 · PMID 39029464 · doi:10.1016/j.ccell.2024.06.012
This dataset
Open GSE249258 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 GSE249258_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 PRJNA1048347 and SRA study SRP475611. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39029464) ↗
Study design
12 conditions, mostly in duplicate
NCI-H1048_DMSO ×2 NCI-H1048_WA-68-VQ71 ×2 NCI-H1048_BRM014 ×2 NCI-H211_DMSO ×2 NCI-H211_WA-68-VQ71 ×2 NCI-H211_BRM014 ×2 NCI-H526_DMSO ×2 NCI-H526_WA-68-VQ71 ×2 +4 more

Supports a between-group comparison across 24 samples.

How we read this: 12 replicated groups read from 24 sample titles; they account for 24 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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