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ATR Is a Critical Dependency Gene Supporting Uveal Melanoma Cell Survival

GSE317502 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/07/31 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)
Topic
Uveal melanomaThis series is part of our curated briefing on it.
Samples
12 samples: 3 × MP38 cells, DMSO treated, sample vs 3 × MP38 cells, VE-822 treated sample vs 3 × 92.1 cells, DMSO treated, sample vs 3 × 92.1 cells, VE-822 treated 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)
GNAQ, GNA11, CYSLTR2, and PLCB4 are well-characterized oncogenic drivers of uveal melanoma (UM). The oncogenic stress induced by these mutations creates a reliance on specific dependency genes that support tumor cell proliferation and survival. However, the genes that broadly contribute to UM cell fitness remain incompletely defined. Using the Dependency Map (DepMap) and Sanger Cancer Dependency bioinformatic resources, we identified ATR (HGNC:882; ATR checkpoint kinase) as a key regulator of UM cell fitness.
Read the full summary ↓
Pharmacologic inhibition of ATR with the selective inhibitor VE-822 in 92.1 and MP38 cells, established models of low-risk and high-risk UM respectively, resulted in DNA double-strand break formation, micronuclei accumulation, and a marked reduction in cell viability. RNA sequencing followed by pathway enrichment analysis was performed to characterize the transcriptional response to ATR inhibition. Transcriptomic profiles from both cell lines support the hypothesis that successful completion of S phase and mitotic progression are critical determinants of survival following ATR inhibition. Further support for the hypothesis that mitotic progression is key to survival for ATR inhibited cells was obtained by treating with VE-822, paclitaxel, or the combination. Combined ATR and microtubule inhibition produced significant synergistic cytotoxicity in both UM models. Collectively, these findings identify ATR as a potential therapeutic vulnerability in uveal melanoma.
This dataset
Open GSE317502 in finder → Find more human RNA-seq datasets → Uveal melanoma 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 GSE317502_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 PRJNA1414276 and SRA study SRP666363. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × MP38 cells, DMSO treated, sample vs 3 × MP38 cells, VE-822 treated sample vs 3 × 92.1 cells, DMSO treated, sample vs 3 × 92.1 cells, VE-822 treated sample

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
More Uveal melanoma datasets

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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.