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| 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
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| 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.
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| 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.
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| 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
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| Street address |
1275 York Ave
|
| City |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (11)
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| 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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