Testing mutual exclusivity of ETS rearranged prostate cancer
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 a...
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| Format: | Online |
| Language: | English |
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Nature Publishing Group
2011
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130188/ |
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pubmed-31301882011-07-12 Testing mutual exclusivity of ETS rearranged prostate cancer Svensson, Maria A LaFargue, Christopher J MacDonald, Theresa Y Pflueger, Dorothee Kitabayashi, Naoki Santa-Cruz, Ashley M Garsha, Karl E Sathyanarayana, Ubaradka G Riley, Janice P Yun, Chol S Nagy, Dea Kosmeder, Jerry W Pestano, Gary A Tewari, Ashutosh K Demichelis, Francesca Rubin, Mark A Research Article 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 5′ 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. Nature Publishing Group 2011-03 2010-10-25 /pmc/articles/PMC3130188/ /pubmed/20975660 http://dx.doi.org/10.1038/labinvest.2010.179 Text en Copyright © 2011 United States and Canadian Academy of Pathology, Inc. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Svensson, Maria A LaFargue, Christopher J MacDonald, Theresa Y Pflueger, Dorothee Kitabayashi, Naoki Santa-Cruz, Ashley M Garsha, Karl E Sathyanarayana, Ubaradka G Riley, Janice P Yun, Chol S Nagy, Dea Kosmeder, Jerry W Pestano, Gary A Tewari, Ashutosh K Demichelis, Francesca Rubin, Mark A |
| spellingShingle |
Svensson, Maria A LaFargue, Christopher J MacDonald, Theresa Y Pflueger, Dorothee Kitabayashi, Naoki Santa-Cruz, Ashley M Garsha, Karl E Sathyanarayana, Ubaradka G Riley, Janice P Yun, Chol S Nagy, Dea Kosmeder, Jerry W Pestano, Gary A Tewari, Ashutosh K Demichelis, Francesca Rubin, Mark A Testing mutual exclusivity of ETS rearranged prostate cancer |
| author_facet |
Svensson, Maria A LaFargue, Christopher J MacDonald, Theresa Y Pflueger, Dorothee Kitabayashi, Naoki Santa-Cruz, Ashley M Garsha, Karl E Sathyanarayana, Ubaradka G Riley, Janice P Yun, Chol S Nagy, Dea Kosmeder, Jerry W Pestano, Gary A Tewari, Ashutosh K Demichelis, Francesca Rubin, Mark A |
| author_sort |
Svensson, Maria A |
| title |
Testing mutual exclusivity of ETS rearranged prostate cancer |
| title_short |
Testing mutual exclusivity of ETS rearranged prostate cancer |
| title_full |
Testing mutual exclusivity of ETS rearranged prostate cancer |
| title_fullStr |
Testing mutual exclusivity of ETS rearranged prostate cancer |
| title_full_unstemmed |
Testing mutual exclusivity of ETS rearranged prostate cancer |
| title_sort |
testing mutual exclusivity of ets rearranged prostate cancer |
| description |
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 5′ 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. |
| publisher |
Nature Publishing Group |
| publishDate |
2011 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130188/ |
| _version_ |
1611463871851134976 |