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EML4-ALK variant-specific genetic interactions shape lung tumorigenesis

GSE301214 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 24 samples Submitted 2025/08/06 Platform GPL34290
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 24 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
24 samples: 8 × Primary Lung Cancer EML-ALK V3, sgSetd2 Sample vs 7 × Primary Lung Cancer EML-ALK V1, sgNeo Sample vs 5 × Primary Lung Cancer EML-ALK V1, sgSetd2 Sample vs 4 × Primary Lung Cancer, EML-ALK V3, sgNeo SampleGroups 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)
Oncogenic fusions of EML4 and ALK occur in ~5% of lung adenocarcinomas. EML4- ALK variants have distinct breakpoints within EML4, but the functional differences among these variants remain poorly understood. Here we use CRISPR/Cas9 somatic genome editing to generate autochthonous mouse models of the two most common EML4-ALK variants and show that V3 is more oncogenic than V1.
Read the full summary ↓
By employing multiplexed genome editing and quantifying the effects of 29 putative tumor suppressor genes on V1- and V3-driven lung cancer growth in vivo we show that many tumor suppressor genes have dramatically variant-specific effects on tumorigenesis. Pharmacogenomic analyses suggest that tumor genotype can also modify responses to therapy. Analysis of a large human EML4-ALK lung cancer cohort identified differences in the genomic landscape depending on the EML4-ALK variant. These findings demonstrate functional heterogeneity between EML4-ALK variants, suggesting that EML4-ALK variants behave more like distinct oncogenes than a uniform entity. More broadly, these findings highlight the dramatic impact of oncogenic fusions partner proteins and coincident tumor suppressor gene alterations on the biology of oncogenic fusion driven cancer.
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 GSE301214_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 PRJNA1284293 and SRA study SRP596094. Searching any of these in the dataset finder brings you back here.

Study design
8 × Primary Lung Cancer EML-ALK V3, sgSetd2 Sample vs 7 × Primary Lung Cancer EML-ALK V1, sgNeo Sample vs 5 × Primary Lung Cancer EML-ALK V1, sgSetd2 Sample vs 4 × Primary Lung Cancer, EML-ALK V3, sgNeo Sample

Supports a between-group comparison across 24 samples.

How we read this: 4 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
Datasets on a similar topic

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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.