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Testing mutual exclusivity of ETS rearranged prostate cancer
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Dept Pathol & Lab Med, Weill Cornell Med Coll, New York NY, USA.
Dept Pathol & Lab Med, Weill Cornell Med Coll, New York NY, USA.
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2011 (English)In: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 91, no 3, p. 404-412Article in journal (Refereed) Published
Abstract [en]

Prostate cancer is a clinically heterogeneous and multifocal disease. More than 80% of patients with prostate cancer harbor multiple geographically discrete cancer foci at the time of diagnosis. Emerging data suggest that these foci are molecularly distinct consistent with the hypothesis that they arise as independent clones. One of the strongest arguments is the heterogeneity observed in the status of E26 transformation specific (ETS) rearrangements between discrete tumor foci. The clonal evolution of individual prostate cancer foci based on recent studies demonstrates intertumoral heterogeneity with intratumoral homogeneity. The issue of multifocality and interfocal heterogeneity is important and has not been fully elucidated due to lack of the systematic evaluation of ETS rearrangements in multiple tumor sites. The current study investigates the frequency of multiple gene rearrangements within the same focus and between different cancer foci. Fluorescence in situ hybridization (FISH) assays were designed to detect the four most common recurrent ETS gene rearrangements. In a cohort of 88 men with localized prostate cancer, we found ERG, ETV1, and ETV5 rearrangements in 51% (44/86), 6% (5/85), and 1% (1/86), respectively. None of the cases demonstrated ETV4 rearrangements. Mutual exclusiveness of ETS rearrangements was observed in the majority of cases; however, in six cases, we discovered multiple ETS or 50 fusion partner rearrangements within the same tumor focus. In conclusion, we provide further evidence for prostate cancer tumor heterogeneity with the identification of multiple concurrent gene rearrangements. Laboratory Investigation (2011) 91, 404-412; doi: 10.1038/labinvest.2010.179; published online 25 October 2010

Place, publisher, year, edition, pages
2011. Vol. 91, no 3, p. 404-412
Keywords [en]
ETS (E26 transformation specific) rearrangements, TMPRSS2-ERG, heterogeneity, prostate cancer
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-28472DOI: 10.1038/labinvest.2010.179ISI: 000287736500007OAI: oai:DiVA.org:oru-28472DiVA, id: diva2:613028
Available from: 2013-03-26 Created: 2013-03-26 Last updated: 2018-05-05Bibliographically approved
In thesis
1. Assessing the ERG rearrangement for clinincal use in patients with prostrate cancer
Open this publication in new window or tab >>Assessing the ERG rearrangement for clinincal use in patients with prostrate cancer
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In Sweden, close to 10 000 men are annually diagnosed with prostate cancer (PCa) and approximately 2400 men die of their disease each year. Today there is no reliable marker that can separate patients who will have an aggressive type of disease that requires treatment, from patients who will have a more indolent clinical course and can be left untreated. This further leads to the current problem of over treatment of men with PCa. Hence, there is an urgent need for reliable prognostic markers that can be used at time of diagnosis. With the discovery of recurrent gene rearrangements in PCa, most commonly ERG rearrangements, hope came that this aberration could play a role in diagnosis and/or prognosis of the disease.

The aim of this thesis was to investigate the clinical implication of ERG rearrangements in the management of PCa.

The work in this thesis supports the findings from previous studies, suggesting that the ERG rearrangement is a sign of a more aggressive type of cancer. The major findings are that in multifocal PCa, the ERG rearranged cancer foci are more prone to metastatic dissemination compared to foci without the ERG rearrangement and that patients harboring the ERG rearrangement have a faster disease progression leading up to earlier start of hormonal treatment. Furthermore, the results add an additional level of complexity in a subset of PCa tumors that harbor multiple gene rearrangements on the cellular level. The result also show that the newly available ERG antibody is highly predictive of ERG rearrangement and is appropriate to use when faced with limitations in tissue amounts.

The findings in this thesis indicate that the ERG rearrangement has a potential role in the clinical management of PCa but further studies arerequired.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2013. p. 65
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 82
Keywords
Prostate cancer, prognosis, biomarkers, ETS genes, ERG rearrangement, fluoroscence in situ hybridization
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-28471 (URN)978-91-7668-918-9 (ISBN)
Public defence
2013-04-26, Wilandersalen, Universitetssjukhuset, Grev Rosengatan 18, 703 62 Örebro, 09:31 (Swedish)
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Available from: 2013-03-26 Created: 2013-03-26 Last updated: 2017-10-17Bibliographically approved

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