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MDM2 degradation overcomes feedback regulation of p53 signaling in Merkel cell carcinoma

GSE292992 Homo sapiens (human) RNA-seq (gene expression) 66 samples Submitted 2026/04/02 Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 66 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
Merkel cell carcinomaThis series is part of our curated briefing on it.
Samples
66 samples: 22 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
Targeted degradation of MDM2 overcomes feedback regulation of p53 signaling in Merkel cell carcinoma modelsThe Journal of clinical investigation · 2026
Summary (written by the submitters)
This study explored the efficacy of MDM2 degraders, KTX-049 and KT-253, in treating Merkel cell carcinoma (MCC), an aggressive skin cancer. MCC tumors often exhibit clonal integration of Merkel cell polyomavirus, with virus-positive (MCCP) and virus-negative (MCCN) tumors showing distinct molecular profiles. MDM2, a target of the ST-MYCL- Tip60 complex in MCCP, inhibits p53-mediated tumor suppression.
Read the full summary ↓
Our results demonstrate that KTX-049 is over 100 times more potent than the MDM2 inhibitor DS- 3032 in MCC cell lines with wild-type p53, effectively degrading MDM2 and activating the p53 response. Mathematical modeling indicates that KTX-049 collapses the p53-MDM2 feedback loop, enhancing its potency. In vivo, KT-253 induced robust and durable p53 pathway activation, producing deep tumor regressions in patient-derived xenograft models. However, the observed resistance was linked to TP53 mutations. These findings highlight the potential of MDM2 degraders as a therapeutic strategy for MCC and other tumor types with wild-type p53 and underscore the need for further investigation of resistance mechanisms and combination therapies.
Published in
Targeted degradation of MDM2 overcomes feedback regulation of p53 signaling in Merkel cell carcinoma models
Ananthapadmanabhan V, Bruno S, Vonk L et al. · The Journal of clinical investigation 2026 · PMID 42383359 · doi:10.1172/JCI199049
This dataset
Open GSE292992 in finder → Find more human RNA-seq datasets → Merkel cell carcinoma 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 GSE292992_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 PRJNA1242314 and SRA study SRP573342. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42383359) ↗
Study design
22 conditions, mostly in triplicate
MKL-1 cells, DMSO control, 24 hours, ×3 MKL-1 cells, KTX-049 treated, 24 hours, ×3 MKL-1 cells, DS-3032 treated, 24 hours, ×3 WaGa cells, DMSO control, 24 hours, ×3 WaGa cells, KTX-049 treated, 24 hours, ×3 WaGa cells, DS-3032 treated, 24 hours, ×3 CDX derived WaGa #E9 cells, DMSO treated, 24 … ×3 CDX derived WaGa #E9 cells, KTX-049 treated, … ×3 +14 more

Supports a case/control comparison: 36 samples read as cases, 6 as controls.

How we read this: 22 replicated groups read from 66 sample titles; they account for 66 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

+ 26 more — browse all 66 samples with per-sample file links →

More Merkel cell carcinoma 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.