SPOP mutation drives prostate neoplasia without stabilizing oncogenic transcription factor ERG.

Shoag, Jonathan; Liu, Deli; Blattner, Mirjam; Sboner, Andrea; Park, Kyung; Deonarine, Lesa; Robinson, Brian D; Mosquera, Juan Miguel; Chen, Yu; Rubin, Mark Andrew; Barbieri, Christopher E (2018). SPOP mutation drives prostate neoplasia without stabilizing oncogenic transcription factor ERG. Journal of clinical investigation, 128(1), pp. 381-386. American Society for Clinical Investigation 10.1172/JCI96551

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Nearly 50% of prostate cancers harbor gene fusions that lead to overexpression of the transcription factor ERG, while a mutually exclusive 10% of prostate cancers harbor recurrent mutations in the gene encoding the E3 ubiquitin ligase SPOP. Recent reports suggest that SPOP acts as a ubiquitin ligase for ERG and propose that ERG stabilization is the oncogenic effector of SPOP mutation. Here, we used human prostate cancer samples and showed that the vast majority of human SPOP-mutant cancers do not express ERG. Comparison of SPOP-mutant and ERG-fusion organoid models showed evidence of divergent, rather than common, transcriptional programs. Furthermore, expression of prostate cancer-associated SPOP mutations in genetically engineered mouse models of SPOP-mutant prostate cancer did not result in the expression of ERG protein in histologically normal prostate glands, high-grade prostatic intraepithelial neoplasia, invasive adenocarcinoma, or prostate organoids. In summary, we found no evidence that ERG is an effector of SPOP mutation in human prostate cancer or mouse models.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie

UniBE Contributor:

Rubin, Mark Andrew

Subjects:

500 Science
500 Science > 570 Life sciences; biology

ISSN:

0021-9738

Publisher:

American Society for Clinical Investigation

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

08 Mar 2018 15:04

Last Modified:

23 Oct 2019 05:30

Publisher DOI:

10.1172/JCI96551

PubMed ID:

29202479

Uncontrolled Keywords:

Oncogenes Oncology

BORIS DOI:

10.7892/boris.110703

URI:

https://boris.unibe.ch/id/eprint/110703

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