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SPORE in Prostate Cancer

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

TitleSPOP mutation drives prostate neoplasia without stabilizing oncogenic transcription factor ERG.
Publication TypeJournal Article
Year of Publication2018
AuthorsShoag J, Liu D, Blattner M, Sboner A, Park K, Deonarine L, Robinson BD, Mosquera JMiguel, Chen Y, Rubin MA, Barbieri CE
JournalJ Clin Invest
Volume128
Issue1
Pagination381-386
Date Published2018 Jan 02
ISSN1558-8238
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.

DOI10.1172/JCI96551
Alternate JournalJ. Clin. Invest.
PubMed ID29202479
PubMed Central IDPMC5749531
Grant ListR01 CA193837 / CA / NCI NIH HHS / United States
P50 CA092629 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
K08 CA140946 / CA / NCI NIH HHS / United States
R01 CA125612 / CA / NCI NIH HHS / United States
R01 CA208100 / CA / NCI NIH HHS / United States
K08 CA187417 / CA / NCI NIH HHS / United States
P50 CA211024 / CA / NCI NIH HHS / United States