GEO series

Targeting DCAF5 suppresses SMARCB1-mutant cancer via stabilizing SWI/SNF

GSE215024 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2024/03/22 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 12 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: 12 samples: 3 × G401_GFP_shctrl vs 3 × G401_GFP_shdcaf5 vs 3 × G401_SB1_shctrl vs 3 × G401_SB1_shdcaf5Groups 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: Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNFNature · 2024

Summary (written by the submitters)

While oncogenes can potentially be inhibited with small molecules, the loss of tumor suppressors is more common and presents a conundrum for precision therapy because the proteins are no longer present. SMARCB1-mutant cancers epitomize this challenge because these highly lethal cancers are driven by inactivation of a single gene, a subunit of SWI/SNF chromatin remodeling complexes.

Read the full summary ↓

To generate mechanistic insight into the consequences of SMARCB1 mutation and to seek vulnerabilities, we contributed 16 SMARCB1-mutant cell lines to a near-genomewide CRISPR screen as part of the Cancer Dependency Map1-3. Here we report that the little-studied gene DCAF5 (DDB1-CUL4 Associated Factor 5) is a specific dependency in SMARCB1-mutant cancers. We show that DCAF5 serves a quality control function for SWI/SNF complexes and in the absence of SMARCB1 DCAF5 causes degradation of incompletely assembled SWI/SNF complexes. Upon inhibition of DCAF5 SMARCB1-deficient SWI/SNF complexes re-accumulate, bind to target loci, and restore gene expression to levels sufficient to fully reverse the cancer state, including in a xenograft mouse model. Consequently, cancer results not from the loss of SMARCB1 function per se but rather from DCAF5-mediated degradation of SWI/SNF complexes. These data indicate that therapeutic targeting of DCAF5 may be sufficient to restore substantial SWI/SNF function and reverse cancer phenotypes caused by SMARCB1 loss.

Published in

Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF

Radko-Juettner S, Yue H, Myers JA et al. · Nature 2024 · PMID 38538798 · doi:10.1038/s41586-024-07250-1

This dataset

Open GSE215024 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 GSE215024_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 PRJNA888093 and SRA study SRP401522. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38538798) ↗

Study design

3 × G401_GFP_shctrl vs 3 × G401_GFP_shdcaf5 vs 3 × G401_SB1_shctrl vs 3 × G401_SB1_shdcaf5

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM6620116 G401_GFP_shctrl_rep1 G401_GFP_shctrl
GSM6620117 G401_GFP_shctrl_rep2 G401_GFP_shctrl
GSM6620118 G401_GFP_shctrl_rep3 G401_GFP_shctrl
GSM6620119 G401_GFP_shdcaf5_rep1 G401_GFP_shdcaf5
GSM6620120 G401_GFP_shdcaf5_rep2 G401_GFP_shdcaf5
GSM6620121 G401_GFP_shdcaf5_rep3 G401_GFP_shdcaf5
GSM6620122 G401_SB1_shctrl_rep1 G401_SB1_shctrl
GSM6620123 G401_SB1_shctrl_rep2 G401_SB1_shctrl
GSM6620124 G401_SB1_shctrl_rep3 G401_SB1_shctrl
GSM6620125 G401_SB1_shdcaf5_rep1 G401_SB1_shdcaf5
GSM6620126 G401_SB1_shdcaf5_rep2 G401_SB1_shdcaf5
GSM6620127 G401_SB1_shdcaf5_rep3 G401_SB1_shdcaf5

Datasets on a similar topic

GSE215025 Targeting DCAF5 suppresses SMARCB1-mutant cancer via stabilizing SWI/SNF 94 samples shares dcaf5, swi, snf, smarcb1-mutant, stabilizing, suppresses, targeting
GSE215023 Targeting DCAF5 suppresses SMARCB1-mutant cancer via stabilizing SWI/SNF 58 samples shares dcaf5, swi, snf, smarcb1-mutant, stabilizing, suppresses, targeting
GSE215022 Targeting DCAF5 suppresses SMARCB1-mutant cancer via stabilizing SWI/SNF 24 samples shares dcaf5, swi, snf, smarcb1-mutant, stabilizing, suppresses, targeting
GSE299562 PHIP suppresses NuRD to enable the growth of SWI/SNF-mutant cancers [RNA-seq] 42 samples shares swi, snf, suppresses
GSE315219 PHIP suppresses NuRD to enable the growth of SWI/SNF-mutant cancers 174 samples shares swi, snf, suppresses
GSE299672 PHIP suppresses NuRD to enable the growth of SWI/SNF-mutant cancers [ChIP-seq] 132 samples shares swi, snf, suppresses
GSE323137 Targeting the CHD3 Chromatin Remodeler Exploits a Synthetic Lethal Vulnerability in SWI/SNF-Deficient Cancers via Toxic Derepression of PARD3B 39 samples shares swi, snf, targeting
GSE313838 Androgen receptor-negative prostate cancer is vulnerable to SWI/SNF-targeting degrader molecules 32 samples shares swi, snf, targeting

Search all human RNA-seq datasets in GEO →

Share this dataset

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.