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Amplified dosage of the NKX2-1 lineage transcription factor controls its oncogenic role in lung adenocarcinoma

GSE229542 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 199 samples Submitted 2025/03/25 Platform GPL18573Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 199 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
Homo sapiens (human)
Topic
Lung cancerThis series is part of our curated briefing on it.
Samples
199 samples: 74 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
Amplified dosage of the NKX2-1 lineage transcription factor controls its oncogenic role in lung adenocarcinomaMolecular cell · 2025
SuperSeries — this record groups several sub-series.
Summary (written by the submitters)
This SuperSeries is composed of the SubSeries listed below. Amplification-mediated oncogene overexpression is a critical and widespread driver event in cancer, yet our understanding of how amplification and dosage mediate oncogene regulation is limited. Here, we find that the most significant focal amplification event in lung adenocarcinoma (LUAD) targets a lineage “super-enhancer” near the NKX2-1 lineage transcription factor.
Read the full summary ↓
The NKX2-1 super-enhancer is targeted by focal and co-amplification with NKX2-1 and controls NKX2-1 expression and regulation. We find that NKX2-1 directly controls enhancer accessibility to drive a lineage-addicted state in LUAD. We precisely map the effects of NKX2-1 dosage modulation upon both overexpression and knockdown and identify both linear and non-linear regulation by NKX2-1 dosage. We find that NKX2-1 is a widespread dependency in LUAD cell lines and that NKX2-1 confers persistence to EGFR inhibitors. Our data suggest a defining role for dosage in the oncogenic regulation of amplified NKX2-1 and that amplified NKX2-1 lineage addiction defines LUAD tumors.
Published in
Amplified dosage of the NKX2-1 lineage transcription factor controls its oncogenic role in lung adenocarcinoma
Pulice JL, Meyerson M · Molecular cell 2025 · PMID 40139189 · doi:10.1016/j.molcel.2025.03.001
This dataset
Open GSE229542 in finder → Find more human ChIP / ATAC / CUT&Tag datasets → Lung cancer 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 GSE229542_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA954846 and SRA study SRP432310. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40139189) ↗
Study design
74 conditions, mostly in duplicate
NCI-H358 sgNT RNA-seq ×3 NCI-H358 sgNKX2-1 RNA-seq ×3 NCI-H2087 sgNT RNA-seq ×3 NCI-H2087 sgNKX2-1 RNA-seq ×3 NCI-H441 sgNT RNA-seq ×3 NCI-H441 sgNKX2-1 RNA-seq ×3 NCI-H2087 shLuc ×2 NCI-H2087 shNKX2-1(1) ×2 +111 more

Supports a between-group comparison across 154 samples.

How we read this: 74 replicated groups read from 199 sample titles; they account for 154 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

+ 159 more — browse all 199 samples with per-sample file links →

More Lung cancer datasets

Search all human ChIP / ATAC / CUT&Tag datasets in GEO →

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