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Genetics and Genomics

Acquired copy number variation in prostate tumours: a review of common somatic copy number alterations, how they are formed and their clinical utility

British Journal of Cancer volume 130, pages 347–357 (2024)Cite this article

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Abstract

Prostate cancer is one of the most commonly diagnosed cancers in men and unfortunately, disease will progress in up to a third of patients despite primary treatment. Currently, there is a significant lack of prognostic tests that accurately predict disease course; however, the acquisition of somatic chromosomal variation in the form of DNA copy number variants may help understand disease progression. Notably, studies have found that a higher burden of somatic copy number alterations (SCNA) correlates with more aggressive disease, recurrence after surgery and metastasis. Here we will review the literature surrounding SCNA formation, including the roles of key tumour suppressors and oncogenes (PTEN, BRCA2, NKX3.1, ERG and AR), and their potential to inform diagnostic and prognostic clinical testing to improve predictive value. Ultimately, SCNAs, or inherited germline alterations that predispose to SCNAs, could have significant clinical utility in diagnostic and prognostic tests, in addition to guiding therapeutic selection.

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Fig. 1: Somatic copy number alterations in prostate cancer focussed on in this review.
Fig. 2: Mechanisms of TMPRSS2-ERG formation.

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Funding

DEO is supported by a Research Training PhD scholarship, University of Tasmania (UTAS); KR is supported by a Cancer Council Tasmania Joy & Robert Coghlan/College of Health and Medicine UTAS Postdoctoral Research Fellowship; JLD is supported by a Select Foundation Cancer Research Fellowship, UTAS; LMF is supported by a Williams Oncology Royal Hobart Hospital Research Foundation grant and a Gerald Harvey UTAS Senior Research Fellowship.

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Authors and Affiliations

  1. Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS, 7000, Australia

    Dannielle E. O’Malley, Kelsie Raspin, Phillip E. Melton, Kathryn P. Burdon, Joanne L. Dickinson & Liesel M. FitzGerald

  2. School of Population and Global Health, The University of Western Australia, Crawley, WA, Australia

    Phillip E. Melton

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  1. Dannielle E. O’Malley
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  2. Kelsie Raspin
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DEO: conceptualisation, investigation, writing original draft and writing review and editing; KR: writing review and editing; PM: writing review and editing and supervision; KPB: writing review and editing and supervision; JLD: writing review and editing and supervision; LMF: conceptualisation, writing review and editing, supervision and project administration.

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Correspondence to Liesel M. FitzGerald.

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O’Malley, D.E., Raspin, K., Melton, P.E. et al. Acquired copy number variation in prostate tumours: a review of common somatic copy number alterations, how they are formed and their clinical utility. Br J Cancer 130, 347–357 (2024). https://doi.org/10.1038/s41416-023-02485-7

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