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Neratinib, a pan ERBB/HER inhibitor, restores sensitivity of PTEN-null, BRAFV600E melanoma to BRAF/MEK inhibition

GSE255541 Homo sapiens (human) RNA-seq (gene expression) 45 samples Submitted 2024/04/23 Platform GPL20301
At a glance

RNA-seq (gene expression) · human · 45 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
MelanomaThis series is part of our curated briefing on it.
Samples
45 samples: 15 conditions, mostly in triplicateGroups 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
Neratinib, a pan ERBB/HER inhibitor, restores sensitivity of PTEN-null, BRAFV600E melanoma to BRAF/MEK inhibitionFrontiers in oncology · 2024
Summary (written by the submitters)
Approximately 50% of melanomas harbor an activating BRAFV600E mutation. Standard of care involves a combination of inhibitors targeting mutant BRAF and MEK1/2, the substrate for BRAF in the MAPK pathway. PTEN loss of function mutations occur in 40% of BRAFV600E melanomas, resulting in increased PI3K/AKT activity that enhances resistance to BRAF/MEK combination inhibitor therapy.
Read the full summary ↓
To compare the response of PTEN null to PTEN wild type cells in an isogenic background, CRISPR was used to knock out PTEN a melanoma cell line that harbors a BRAFV600E mutation. RNA sequencing and functional kinome analysis revealed the loss of PTEN led to an induction of FOXD3 and an increase in expression of the FOXD3 target gene, ERBB3/HER3. Inhibition of BRAF and MEK1/2 in PTEN null, BRAFV600Ecells dramatically induced expression of ERBB3/HER3 relative to wild type cells. A synergy screen of epigenetic modifiers and kinase inhibitors in combination with BRAFi/MEKi identified the pan ERBB/HER inhibitor, neratinib, as reversing the resistance observed in PTEN null, BRAFV600Ecells. The findings indicate that PTEN null BRAFV600E melanoma exhibits increased reliance on ERBB/HER signaling when treated with clinically approved BRAFi/MEKi combinations. Future studies are warranted to test neratinib reversal of resistance in patient melanomas expressing ERBB3/HER3 in combination with its dimerization partner ERBB2/HER2.
Published in
Neratinib, a pan ERBB/HER inhibitor, restores sensitivity of PTEN-null, BRAFV600E melanoma to BRAF/MEK inhibition
DuBose E, Bevill SM, Mitchell DK et al. · Frontiers in oncology 2024 · PMID 38854737 · doi:10.3389/fonc.2024.1191217
This dataset
Open GSE255541 in finder → Find more human RNA-seq datasets → 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 GSE255541_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 PRJNA1075321 and SRA study SRP489243. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38854737) ↗
Study design
15 conditions, mostly in triplicate
A375 wild type, DMSO, ×3 A375 wild type, dabrafenib/trametinib 1 day (… ×3 A375 wild type, dabrafenib/trametinib 7 day (… ×3 A375 PTEN KO5, DMSO, ×3 A375 PTEN KO5, dabrafenib/trametinib 1 day (a… ×3 A375 PTEN KO5, dabrafenib/trametinib 7 day (c… ×3 A375 PTEN KO11, DMSO, ×3 A375 PTEN KO11, dabrafenib/trametinib 1 day (… ×3 +7 more

Supports a case/control comparison: 12 samples read as cases, 15 as controls.

How we read this: 15 replicated groups read from 45 sample titles; they account for 45 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

+ 5 more — browse all 45 samples with per-sample file links →

More Melanoma datasets

Search all human RNA-seq datasets in GEO →

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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.