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Whilst treatment of primary UM (PUM) is often successful, around 50% of patients develop metastatic disease with poor outcomes, linked to chromosome 3 loss (monosomy 3, M3). Advances in understanding UM cell biology may indicate new therapeutic options. We report that UM exhibits centrosome abnormalities, which in other cancers are associated with increased invasiveness and worse prognosis, but also represent a potential Achilles' heel for cancer\u2010specific therapeutics. Analysis of 75 PUM patient samples revealed both higher centrosome numbers and an increase in centrosomes with enlarged pericentriolar matrix (PCM) compared to surrounding normal tissue, both indicative of centrosome amplification. The PCM phenotype was significantly associated with M3 (<jats:italic>t<\/jats:italic>\u2010test, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Centrosomes naturally enlarge as cells approach mitosis; however, whilst UM with higher mitotic scores had enlarged PCM regardless of genetic status, the PCM phenotype remained significantly associated with M3 in UM with low mitotic scores (ANOVA, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.021) suggesting that this is independent of proliferation. Phenotypic analysis of patient\u2010derived cultures and established UM lines revealed comparable levels of centrosome amplification in PUM cells to archetypal triple\u2010negative breast cancer cell lines, whilst metastatic UM (MUM) cell lines had even higher levels. Importantly, many UM cells also exhibit centrosome clustering, a common strategy employed by other cancer cells with centrosome amplification to survive cell division. As UM samples with M3 display centrosome abnormalities indicative of amplification, this phenotype may contribute to the development of MUM, suggesting that centrosome de\u2010clustering drugs may provide a novel therapeutic approach.<\/jats:p>","DOI":"10.1002\/cjp2.272","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T02:25:06Z","timestamp":1651026306000},"page":"383-394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Aggressive uveal melanoma displays a high degree of centrosome amplification, opening the door to therapeutic intervention"],"prefix":"10.1002","volume":"8","author":[{"given":"Dorota","family":"Sabat\u2010Po\u015bpiech","sequence":"first","affiliation":[{"name":"Molecular Physiology and Cell Signalling, Institute of Systems Molecular &amp; Integrative Biology University of Liverpool  Liverpool UK"},{"name":"Molecular and Clinical Cancer Medicine, Institute of Systems Molecular &amp; Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Fabian\u2010Kolpanowicz","sequence":"additional","affiliation":[{"name":"Biomedical and Life Sciences, Faculty of Health and Medicine Lancaster University  Lancaster UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4440-2576","authenticated-orcid":false,"given":"Helen","family":"Kalirai","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Cancer Medicine, Institute of Systems Molecular &amp; Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Kipling","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Cancer Medicine, Institute of Systems Molecular &amp; Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1464-2069","authenticated-orcid":false,"given":"Sarah E","family":"Coupland","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Cancer Medicine, Institute of Systems Molecular &amp; Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2191-2001","authenticated-orcid":false,"given":"Judy M","family":"Coulson","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Cell Signalling, Institute of Systems Molecular &amp; Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3170-9966","authenticated-orcid":false,"given":"Andrew B","family":"Fielding","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Cell Signalling, Institute of Systems 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