GEO series
Dual targeting of processive transcription for Myc-driven circuitry in medulloblastoma [CUT&RUN]
GSE267470
Homo sapiens
Genome binding/occupancy profiling by high throughput sequencing
12 samples
Submitted 2024/11/14
Platform GPL24676
Summary
Medulloblastoma is the most common malignant brain tumor of childhood. The highest-risk tumors are driven by recurrent Myc amplifications (Myc-MB) and experience poorer outcomes despite intensive multimodal therapy. The Myc transcription factor defines core regulatory circuitry for these tumors and acts to broadly amplify downstream pro-survival transcriptional programs. Therapeutic targeting of Myc directly has proven elusive, but inhibiting transcriptional cofactors may present an indirect means of drugging the oncogenic transcriptional circuitry sustaining Myc-MB. Independent CRISPR-Cas9 screens were pooled to identify conserved dependencies in Myc-MB. We performed chromatin conformation capture (Hi-C) from primary patient Myc-MB samples to map enhancer-promoter interactions. We then treated in vitro and xenograft models with the dual CDK9/7 inhibitor zotiraciclib to evaluate effect on Myc-driven programs and tumor growth. Eight CRISPR-Cas9 screens performed across three independent labs identify CDK9 as a conserved dependency in Myc-MB. Myc-MB cells are susceptible to CDK9 inhibition, which is synergistic with concurrent inhibition of CDK7. The dual CDK9/7 inhibitor zotiraciclib disrupts enhancer-promoter activity in Myc-MB and downregulates Myc-driven transcriptional programs, exerting potent anti-tumor effect.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE267470_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 12 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1111557 and SRA study SRP507676. Searching any of these in the dataset finder brings you back here.
Study design
12 conditions, each sampled once — no replicated groups
Read from 12 sample titles: 12 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8267128 D458 cells, IgG, DMSO, replicate 1, ChIP
- GSM8267129 D458 cells, IgG, DMSO, replicate 2, ChIP
- GSM8267130 D458 cells, Myc, DMSO, replicate 1, ChIP
- GSM8267131 D458 cells, Myc, DMSO, replicate 2, ChIP
- GSM8267132 D458 cells, IgG, TG02, replicate 1, ChIP
- GSM8267133 D458 cells, IgG, TG02, replicate 2, ChIP
- GSM8267134 D458 cells, Myc, TG02, replicate 1, ChIP
- GSM8267135 D458 cells, Myc, TG02, replicate 2, ChIP
- GSM8267136 D458 cells, H3K4me1, replicate 1, ChIP
- GSM8267137 D458 cells, H3K4me1, replicate 2, ChIP
- GSM8267138 D458 cells, IgG, replicate 1, ChIP
- GSM8267139 D458 cells, IgG, replicate 2, ChIP
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