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Series GSE98809 Query DataSets for GSE98809
Status Public on Jun 08, 2017
Title Loss of Function Mutations in ETS2 Repressor Factor (ERF) Reveal a Balance Between Positive and Negative ETS Factors Controlling Prostate Oncogenesis [VCaP ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Half of prostate cancers are caused by a gene-fusion that enables androgens to drive expression of the normally silent ETS transcription factor ERG in luminal prostate cells1-4. Recent prostate cancer genomic landscape studies5-10 have reported rare but recurrent point mutations in the ETS repressor ERF11. Here we show these ERF mutations cause decreased protein stability and ERF mutant tumours are mostly exclusive from those with ERG fusions. ERF loss recapitulates the morphologic and phenotypic features of ERG gain in primary mouse prostate tissue, including expansion of the androgen receptor (AR) transcriptional repertoire, and ERF has tumour suppressor activity in the same genetic background of PTEN loss that yields oncogenic activity by ERG. Furthermore, in a human prostate cancer model of ERG gain and wild-type ERF, ChIP-seq studies indicate that ERG inhibits the ability of ERF to bind DNA at consensus ETS sites. Consistent with a competition model, ERF loss rescues ERG-positive prostate cancer cells from ERG dependency. Collectively, these data provide evidence that the oncogenicity of ERG is mediated, in part, by displacement of ERF and raise the larger question of whether other gain-of-function oncogenic transcription factors might also inactivate endogenous tumour suppressors.
 
Overall design VCaP cells were infected with Tet-inducible shERG lentivirus and selected with antibiotics. Subsequently, cells were treated with 100ng/mL doxycycline vs vehicle. Samples were then sonicated and genomic DNA extracted for ChIP-seq.
 
Contributor(s) Bose R, Wang P, Patruno A, Zhao Y, Zheng D, Sawyers CL
Citation(s) 28614298
Submission date May 11, 2017
Last update date May 15, 2019
Contact name Rohit Bose
Organization name Memorial Sloan Kettering Cancer Center
Street address 1275 York Ave
City New York
ZIP/Postal code 10065
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (11)
GSM2612448 VCaP green replicate one
GSM2612449 VCaP green replicate two
GSM2612450 VCaP red replicate one
This SubSeries is part of SuperSeries:
GSE83653 Loss of Function Mutations in ETS2 Repressor Factor (ERF) Reveal a Balance Between Positive and Negative ETS Factors Controlling Prostate Oncogenesis
Relations
BioProject PRJNA386288
SRA SRP106868

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Supplementary file Size Download File type/resource
GSE98809_RAW.tar 1.7 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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