GEO series
Dynamic Chromatin Alteration Induces Oncogenic Hijacking by Nuclear Factor I Family Proteins for Medulloblastoma Progression
GSE241602
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
30 samples
Submitted 2024/05/03
Platform GPL24247Platform GPL24676
Summary
The cancer-specific epigenome is the critical scaffold on which genetic programs work to positively promote cancer growth and progression. Understanding and appropriately disrupting this epigenome will lead to the discovery of new, more extensive and effective therapies in addition to conventional personalized medicine that relies on genomic mutations. However, the epigenomic changes during the process from normal cells to cancer formation as well as the molecules involved in the maintenance of the aberrant epigenome are still poorly characterized, and the development of epigenome-based therapeutics is therefore undeniably stagnant. To address this issue, we here focus on SHH-subgroup medulloblastoma, a representative pediatric brain tumor for which we developed a reliable mouse model to capture the epigenomic changes that cerebellar granule cells, the cells of origin, undergo during tumorigenesis. By comparing the epigenomes of the different stages of transforming cells, we identified NFI family of developmental factors as oncogenic regulators in the epigenome of pre-cancerous and cancerous cells, which they also contribute to maintain. Furthermore, we report pharmacological experiments demonstrating that inhibition of NFIB methylation blocks tumor growth and increases sensitivity to molecularly targeted drugs by disrupting the cancer epigenome. Thus, this study is a unique example of how epigenomic studies of cancer have led directly to therapeutic insights, and similar approaches in various cancers would accelerate the establishment of novel therapies.
Published in
Shiraishi R, Cancila G, Kumegawa K et al.
· Developmental cell 2024
· PMID 38834071
· doi:10.1016/j.devcel.2024.05.013
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE241602_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 30 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1008757 and SRA study SRP456820. Searching any of these in the dataset finder brings you back here.
Study design
9 conditions, mostly in triplicate
PDX12, PDX, NC, biol ×4
PDX12, PDX, shNFIA, biol ×4
PDX12, PDX, shNFIB, biol ×4
BT084, PDX, NC, biol ×3
BT084, PDX, shNFIA, biol ×3
BT084, PDX, shNFIB, biol ×3
VDR, cell line, NC, biol ×3
VDR, cell line, shNFIA, biol ×3
+1 more
Supports a between-group comparison across 30 samples.
9 replicated groups read from 30 sample titles; they account for 30 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM7731549 BT084, PDX, NC, biol rep1
- GSM7731550 BT084, PDX, shNFIA, biol rep1
- GSM7731551 BT084, PDX, shNFIB, biol rep1
- GSM7731552 BT084, PDX, NC, biol rep2
- GSM7731553 BT084, PDX, shNFIA, biol rep2
- GSM7731554 BT084, PDX, shNFIB, biol rep2
- GSM7731555 BT084, PDX, NC, biol rep3
- GSM7731556 BT084, PDX, shNFIA, biol rep3
- GSM7731557 BT084, PDX, shNFIB, biol rep3
- GSM7731558 PDX12, PDX, NC, biol rep1
- GSM7731559 PDX12, PDX, shNFIA, biol rep1
- GSM7731560 PDX12, PDX, shNFIB, biol rep1
- GSM7731561 PDX12, PDX, NC, biol rep2
- GSM7731562 PDX12, PDX, shNFIA, biol rep2
- GSM7731563 PDX12, PDX, shNFIB, biol rep2
- GSM7731564 PDX12, PDX, NC, biol rep3
- GSM7731565 PDX12, PDX, shNFIA, biol rep3
- GSM7731566 PDX12, PDX, shNFIB, biol rep3
- GSM7731567 PDX12, PDX, NC, biol rep4
- GSM7731568 PDX12, PDX, shNFIA, biol rep4
- GSM7731569 PDX12, PDX, shNFIB, biol rep4
- GSM7731570 VDR, cell line, NC, biol rep1
- GSM7731571 VDR, cell line, shNFIA, biol rep1
- GSM7731572 VDR, cell line, shNFIB, biol rep1
- GSM7731573 VDR, cell line, NC, biol rep2
- GSM7731574 VDR, cell line, shNFIA, biol rep2
- GSM7731575 VDR, cell line, shNFIB, biol rep2
- GSM7731576 VDR, cell line, NC, biol rep3
- GSM7731577 VDR, cell line, shNFIA, biol rep3
- GSM7731578 VDR, cell line, shNFIB, biol rep3
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