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dc.contributor.authorFraser, M.
dc.contributor.authorLivingstone, J.
dc.contributor.authorWrana, J. L.
dc.contributor.authorFinelli, A.
dc.contributor.authorHe, H. H.
dc.contributor.authorvan der Kwast, T.
dc.contributor.authorZlotta, A. R.
dc.contributor.authorBristow, Robert G
dc.contributor.authorBoutros, P. C.
dc.date.accessioned2021-11-26T10:04:46Z
dc.date.available2021-11-26T10:04:46Z
dc.date.issued2021en
dc.identifier.citationFraser M, Livingstone J, Wrana JL, Finelli A, He HH, van der Kwast T, et al. Somatic driver mutation prevalence in 1844 prostate cancers identifies ZNRF3 loss as a predictor of metastatic relapse [Internet]. Vol. 12, Nature Communications. Springer Science and Business Media LLC; 2021.en
dc.identifier.pmid34716314en
dc.identifier.doi10.1038/s41467-021-26489-0en
dc.identifier.urihttp://hdl.handle.net/10541/624800
dc.description.abstractDriver gene mutations that are more prevalent in metastatic, castration-resistant prostate cancer (mCRPC) than localized disease represent candidate prognostic biomarkers. We analyze 1,844 localized (1,289) or mCRPC (555) tumors and quantify the prevalence of 113 somatic driver single nucleotide variants (SNVs), copy number aberrations (CNAs), and structural variants (SVs) in each state. One-third are significantly more prevalent in mCRPC than expected while a quarter are less prevalent. Mutations in AR and its enhancer are more prevalent in mCRPC, as are those in TP53, MYC, ZNRF3 and PRKDC. ZNRF3 loss is associated with decreased ZNRF3 mRNA abundance, WNT, cell cycle & PRC1/2 activity, and genomic instability. ZNRF3 loss, RNA downregulation and hypermethylation are prognostic of metastasis and overall survival, independent of clinical and pathologic indices. These data demonstrate a strategy for identifying biomarkers of localized cancer aggression, with ZNRF3 loss as a predictor of metastasis in prostate cancer.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1038/s41467-021-26489-0en
dc.titleSomatic driver mutation prevalence in 1844 prostate cancers identifies ZNRF3 loss as a predictor of metastatic relapseen
dc.typeArticleen
dc.contributor.departmentDepartment of Surgery, Division of Urology, University of Toronto, Toronto, ON, Canada.en
dc.identifier.journalNature Communicationsen
dc.description.noteen]
refterms.dateFOA2021-12-01T10:35:58Z


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