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SPOP mutation drives prostate neoplasia without stabilizing oncogenic transcription factor ERG
Jonathan Shoag, … , Mark A. Rubin, Christopher E. Barbieri
Jonathan Shoag, … , Mark A. Rubin, Christopher E. Barbieri
Published December 4, 2017
Citation Information: J Clin Invest. 2018;128(1):381-386. https://doi.org/10.1172/JCI96551.
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Concise Communication Oncology

SPOP mutation drives prostate neoplasia without stabilizing oncogenic transcription factor ERG

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Abstract

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.

Authors

Jonathan Shoag, Deli Liu, Mirjam Blattner, Andrea Sboner, Kyung Park, Lesa Deonarine, Brian D. Robinson, Juan Miguel Mosquera, Yu Chen, Mark A. Rubin, Christopher E. Barbieri

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Figure 1

SPOP mutation does not result in ERG protein expression by immunohistochemistry in normal or neoplastic murine prostate.

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SPOP mutation does not result in ERG protein expression by immunohistoch...
(A) Histologically normal prostate from mice conditionally expressing SPOP-F133V in the prostate (Rosa26SPOP-F133V Pten+/+ Pb-Cre). A and B scale bars: 50 μm. (B) SPOP-mutation-driven murine HG-PIN (Rosa26SPOP-F133V PtenL/+ Pb-Cre). (C) SPOP-mutation-driven murine prostate adenocarcinoma. (Rosa26SPOP-F133V PtenL/L Pb-Cre). Insets show ERG staining in endothelial cells (arrow) adjacent to SPOP-mutant-expressing prostate cells. SPOP-F133V transgenic expression confirmed by GFP expression. A minimum of 3 mice were utilized for each condition. Representative sections are shown. Scale bars: 50 μm in right images of C, 500 μm in left and center images of C.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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