SPOP mutation drives prostate neoplasia without stabilizing oncogenic transcription factor ERG Journal Article
| Authors: | Shoag, J.; Liu, D.; Blattner, M.; Sboner, A.; Park, K.; Deonarine, L.; Robinson, B. D.; Mosquera, J. M.; Chen, Y.; Rubin, M. A.; Barbieri, C. E. |
| Article Title: | SPOP mutation drives prostate neoplasia without stabilizing oncogenic transcription factor ERG |
| 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. |
| Keywords: | immunohistochemistry; controlled study; unclassified drug; gene mutation; human cell; nonhuman; comparative study; protein function; animal cell; mouse; animal tissue; gene overexpression; animal experiment; animal model; protein stability; genetic transcription; carcinogenesis; prostate cancer; oncogene; tumor protein; gene fusion; transcription factor erg; cytoplasm; invasive carcinoma; prostate adenocarcinoma; prostatic intraepithelial neoplasia; molecular pathology; high grade prostatic intraepithelial neoplasia; human; male; priority journal; article; prostate epithelium cell; prostate tissue; spop protein |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 128 |
| Issue: | 1 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2018-01-02 |
| Start Page: | 381 |
| End Page: | 386 |
| Language: | English |
| DOI: | 10.1172/jci96551 |
| PROVIDER: | scopus |
| PUBMED: | 29202479 |
| PMCID: | PMC5749531 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2018 -- Source: Scopus |
