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| Status |
Public on Oct 23, 2014 |
| Title |
Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor (ChIP-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Small cell lung cancer (SCLC) is an aggressive disease with high mortality. The identification of effective pharmacological strategies to target SCLC biology represents an urgent need. Using a high-throughput cellular screen of a diverse chemical library we observe that SCLC is sensitive to transcription-targeting drugs, and in particular to THZ1, a newly identified covalent inhibitor of cyclin-dependent kinase 7 (CDK7). We find that expression of super-enhancer associated transcription factor genes including MYC family proto-oncogenes and neuroendocrine lineage-specific factors are highly vulnerability to THZ1 treatment. We propose that downregulation of these transcription factors contributes, in part, to SCLC sensitivity to transcriptional inhibitors and that THZ1 represents a novel treatment paradigm for targeted SCLC therapy.
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| Overall design |
ChIP-Seq for H3K27ac in small cell lung cancer lines
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| Contributor(s) |
Christensen CL, Kwiatkowski N, Abraham BJ, Carretero J, Al-shahrour F, Zhang T, Chipumoro E, Hurter-Sprie G, Akbay EA, Altabef A, Zhang J, Shimamura T, Capalletti M, Reibel JB, Cavanaugh J, Gao P, Liu Y, Michaelsen SR, Poulsen HS, Aref AR, Barbie DA, Bradner JE, George R, Gray NS, Young RA, Wong KK |
| Citation(s) |
25490451 |
| Submission date |
Oct 16, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Richard A Young |
| E-mail(s) |
young_computation@wi.mit.edu
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| Phone |
617-258-5219
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| Organization name |
Whitehead Institute for Biomedical Research
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| Lab |
Young Lab
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| Street address |
9 Cambridge Center
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE62614 |
Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor |
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| Relations |
| BioProject |
PRJNA264058 |
| SRA |
SRP048975 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE62412_RAW.tar |
1.3 Gb |
(http)(custom) |
TAR (of WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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