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    Somatic driver mutation prevalence in 1844 prostate cancers identifies ZNRF3 loss as a predictor of metastatic relapse

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    Authors
    Fraser, M.
    Livingstone, J.
    Wrana, J. L.
    Finelli, A.
    He, H. H.
    van der Kwast, T.
    Zlotta, A. R.
    Bristow, Robert G
    Boutros, P. C.
    Affiliation
    Department of Surgery, Division of Urology, University of Toronto, Toronto, ON, Canada.
    Issue Date
    2021
    
    Metadata
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    Abstract
    Driver 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.
    Citation
    Fraser 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.
    Journal
    Nature Communications
    URI
    http://hdl.handle.net/10541/624800
    DOI
    10.1038/s41467-021-26489-0
    PubMed ID
    34716314
    Additional Links
    https://dx.doi.org/10.1038/s41467-021-26489-0
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-021-26489-0
    Scopus Count
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    All Paterson Institute for Cancer Research

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