GEO series
Loss of NOTCH2 Creates a TRIM28-Dependent Vulnerability in Small Cell Lung Cancer [ChIP-seq]
GSE297358
Homo sapiens; Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
29 samples
Submitted 2025/07/10
Platform GPL34284Platform GPL34290
Summary
Small cell lung cancer (SCLC) is a highly aggressive malignancy that lacks effective targeted therapies, in part due to frequent loss-of-function mutations in tumor suppressors and the absence of recurrent oncogenic drivers. Approximately 15% of SCLCs harbor inactivating mutations in NOTCH1 or NOTCH2, and most neuroendocrine-high SCLCs exhibit low NOTCH activity. Using CRISPR/Cas9 screening in primary cell lines derived from NOTCH1/2-isogenic SCLC genetically engineered mouse models, we identified TRIM28 as a synthetic lethal dependency in NOTCH2-inactivated SCLCs. Loss of TRIM28 in this context robustly induced expression of endogenous retroviruses, activated viral sensing pathways, and triggered a type I interferon response. Mechanistically, NOTCH2 inactivation increased reliance on TRIM28-mediated ERV silencing, creating a hyper-dependence on TRIM28 via the STING–MAVS–TBK1 axis. Notably, TRIM28 was essential for tumor growth only in the setting of NOTCH2 loss. These findings identify TRIM28 as a potential therapeutic target in NOTCH2-deficient or low-NOTCH2-expressing SCLC.
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE297358_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 29 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1263597 and SRA study SRP585707. Searching any of these in the dataset finder brings you back here.
Study design
9 conditions, mostly in duplicate
HA ChIP-seq on H1048 NOTCH2-WT TRIM28-HA Over… ×2
HA ChIP-seq on 1014 NOTCH2-WT TRIM28-dTAG-HA … ×2
HA ChIP-seq on 1014 NOTCH2-Inactivated TRIM28… ×2
H3K27ac ChIP-seq on 1014 NOTCH2-WT TRIM28-dTA… ×2
H3K27ac ChIP-seq on 1014 NOTCH2-WT TRIM28-dTA… ×2
H3K27ac ChIP-seq on 1014 NOTCH2-Inactivated T… ×2
H3K9me3 ChIP-seq on 1014 NOTCH2-WT TRIM28-dTA… ×2
H3K9me3 ChIP-seq on 1014 NOTCH2-Inactivated T… ×2
+12 more
Supports a case/control comparison: 3 samples read as cases, 10 as controls.
9 replicated groups read from 29 sample titles; they account for 18 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8989351 HA ChIP-seq on H1048 NOTCH2-WT TRIM28-HA Overexpressing cells Rep1
- GSM8989352 HA ChIP-seq on H1048 NOTCH2-WT TRIM28-HA Overexpressing cells Rep2
- GSM8989353 HA ChIP-seq on 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells Rep1
- GSM8989354 HA ChIP-seq on 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells Rep2
- GSM8989355 HA ChIP-seq on 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells Rep1
- GSM8989356 HA ChIP-seq on 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells Rep2
- GSM8989357 H3K27ac ChIP-seq on 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells with DMSO Rep1
- GSM8989358 H3K27ac ChIP-seq on 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells with DMSO Rep2
- GSM8989359 H3K27ac ChIP-seq on 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells with dTAGV1 Rep1
- GSM8989360 H3K27ac ChIP-seq on 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells with dTAGV1 Rep2
- GSM8989361 H3K27ac ChIP-seq on 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells with DMSO Rep1
- GSM8989362 H3K27ac ChIP-seq on 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells with DMSO Rep2
- GSM8989363 H3K27ac ChIP-seq on 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells with dTAGV1 Rep1
- GSM8989364 H3K27ac ChIP-seq on 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells with dTAGV1 Rep2
- GSM8989365 H3K9me3 ChIP-seq on 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells with DMSO Rep1
- GSM8989366 H3K9me3 ChIP-seq on 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells with DMSO Rep2
- GSM8989367 H3K9me3 ChIP-seq on 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells with dTAGV1 Rep1
- GSM8989368 H3K9me3 ChIP-seq on 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells with dTAGV1 Rep2
- GSM8989369 H3K9me3 ChIP-seq on 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells with DMSO Rep1
- GSM8989370 H3K9me3 ChIP-seq on 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells with DMSO Rep2
- GSM8989371 H3K9me3 ChIP-seq on 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells with dTAGV1 Rep1
- GSM8989372 H3K9me3 ChIP-seq on 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells with dTAGV1 Rep2
- GSM8989373 Input of 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells with DMSO
- GSM8989374 Input of 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells witt dTAGV1
- GSM8989375 Input of 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells with DMSO
- GSM8989376 Input of 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells witt dTAGV1
- GSM8989377 Input of 1014 NOTCH2-WT TRIM28-dTAG-HA knock-in cells for HA-ChIP
- GSM8989378 Input of 1014 NOTCH2-Inactivated TRIM28-dTAG-HA knock-in cells for HA-ChIP
- GSM8989379 Input of H1048 NOTCH2-WT TRIM28-HA Overexpressing cells
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