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    The influence of BRCA2 mutation on localized prostate cancer

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    Authors
    Taylor, RA
    Fraser, M
    Rebello, R
    Boutros, PC
    Murphy, DG
    Bristow, Robert G
    Risbridger, GP
    Affiliation
    Monash Partners Comprehensive Cancer Consortium and Cancer Program, Biomedicine Discovery Institute, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology and Department of Physiology, Monash University, Melbourne, Victoria, Australia
    Issue Date
    2019
    
    Metadata
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    Abstract
    A key challenge in the management of localized prostate cancer is the identification of men with a high likelihood of progression to an advanced, incurable stage. Patients who harbour germline BRCA2 mutations have worse clinical outcomes than noncarriers when treated with surgery or radiotherapy. Insights from different disciplines have improved our understanding of why patients with BRCA2-mutant tumours have a high likelihood of failing on conventional management after diagnosis. Treatment-naive BRCA2-mutant tumours are defined by aggressive clinical and molecular features early in the disease course, and the genomic landscape of these BRCA2-mutant tumours is characterized by a unique molecular profile and higher genomic instability than noncarrier tumours. Moreover, BRCA2-mutant tumours commonly show the concurrent presence of the intraductal carcinoma of the prostate (IDCP) pathology, a poor prognostic indicator. Subclonal analyses have revealed that IDCP and invasive adenocarcinoma in BRCA2-mutant tumours can arise from the same ancestral clone, implying that a temporal evolutionary trajectory exists. Finally, functional studies have shown that BRCA2-mutant tumours can harbour a subpopulation of cancer cells that can tolerate castration de novo, enabling the tumour to evade androgen deprivation therapy. Importantly, future challenges remain regarding how to best model the biology underpinning this aggressive phenotype and translate these findings to improve clinical outcomes.
    Citation
    Taylor RA, Fraser M, Rebello RJ, Boutros PC, Murphy DG, Bristow RG, et al. The influence of BRCA2 mutation on localized prostate cancer. Nat Rev Urol. 2019 Feb 26.
    Journal
    Nature Reviews Urology
    URI
    http://hdl.handle.net/10541/621638
    DOI
    10.1038/s41585-019-0164-8
    PubMed ID
    30808988
    Additional Links
    https://dx.doi.org/10.1038/s41585-019-0164-8
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41585-019-0164-8
    Scopus Count
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    All Paterson Institute for Cancer Research

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