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Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer

Prostate cancer is notorious for its heterogeneity, which poses a problem for the applicability of diagnostic molecular markers. However, heterogeneity analysis can provide valuable information on the chronology in which molecular alterations arise. Here, we constructed a heterogeneity tissue microa...

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Autores principales: Kluth, Martina, Meyer, David, Krohn, Antje, Freudenthaler, Fabian, Bauer, Melanie, Salomon, Georg, Heinzer, Hans, Michl, Uwe, Steurer, Stefan, Simon, Ronald, Sauter, Guido, Schlomm, Thorsten, Minner, Sarah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826178/
https://www.ncbi.nlm.nih.gov/pubmed/26684029
http://dx.doi.org/10.18632/oncotarget.6597
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author Kluth, Martina
Meyer, David
Krohn, Antje
Freudenthaler, Fabian
Bauer, Melanie
Salomon, Georg
Heinzer, Hans
Michl, Uwe
Steurer, Stefan
Simon, Ronald
Sauter, Guido
Schlomm, Thorsten
Minner, Sarah
author_facet Kluth, Martina
Meyer, David
Krohn, Antje
Freudenthaler, Fabian
Bauer, Melanie
Salomon, Georg
Heinzer, Hans
Michl, Uwe
Steurer, Stefan
Simon, Ronald
Sauter, Guido
Schlomm, Thorsten
Minner, Sarah
author_sort Kluth, Martina
collection PubMed
description Prostate cancer is notorious for its heterogeneity, which poses a problem for the applicability of diagnostic molecular markers. However, heterogeneity analysis can provide valuable information on the chronology in which molecular alterations arise. Here, we constructed a heterogeneity tissue microarray (TMA) comprising samples from 10 different tumor areas of 189 prostate cancers each in order to study the sequence of two frequent molecular alterations, i.e. 6q15 deletion and TMPRSS2:ERG fusion. Previous work shows a marked inverse relationship between these alterations, suggesting that presence of one of these alterations might impact development of the other. 6q15 deletion was analyzed by fluorescence in situ hybridization and ERG-expression by immunohistochemistry. Only 6.6% of 334 ERG-positive but 28.4% of 440 ERG-negative TMA spots showed 6q15 deletions (p < 0.0001). A breakdown of these data to the level of tumor foci revealed 6q deletions in 138 tumor foci that were large enough to have at least 3 analyzable TMA spots. These included 42 tumor foci with homogeneous ERG positivity and 16 with homogeneous 6q15 deletions. Remarkably, six of the 42 homogeneously ERG-positive tumor foci (14.3%) harbored small 6q15-deleted areas, but none of the 34 6q15-deleted foci showed areas of ERG positivity (p = 0.022). In conclusion, our data suggest that ERG-fusion can precede 6q15 deletion, but not vice versa. The complete absence of ERG-positive tumor areas in 6q15-deleted tumor foci further suggest that the functional consequences of 6q15 deletions may prevent the development of TMPRSS2:ERG fusions.
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spelling pubmed-48261782016-05-09 Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer Kluth, Martina Meyer, David Krohn, Antje Freudenthaler, Fabian Bauer, Melanie Salomon, Georg Heinzer, Hans Michl, Uwe Steurer, Stefan Simon, Ronald Sauter, Guido Schlomm, Thorsten Minner, Sarah Oncotarget Research Paper Prostate cancer is notorious for its heterogeneity, which poses a problem for the applicability of diagnostic molecular markers. However, heterogeneity analysis can provide valuable information on the chronology in which molecular alterations arise. Here, we constructed a heterogeneity tissue microarray (TMA) comprising samples from 10 different tumor areas of 189 prostate cancers each in order to study the sequence of two frequent molecular alterations, i.e. 6q15 deletion and TMPRSS2:ERG fusion. Previous work shows a marked inverse relationship between these alterations, suggesting that presence of one of these alterations might impact development of the other. 6q15 deletion was analyzed by fluorescence in situ hybridization and ERG-expression by immunohistochemistry. Only 6.6% of 334 ERG-positive but 28.4% of 440 ERG-negative TMA spots showed 6q15 deletions (p < 0.0001). A breakdown of these data to the level of tumor foci revealed 6q deletions in 138 tumor foci that were large enough to have at least 3 analyzable TMA spots. These included 42 tumor foci with homogeneous ERG positivity and 16 with homogeneous 6q15 deletions. Remarkably, six of the 42 homogeneously ERG-positive tumor foci (14.3%) harbored small 6q15-deleted areas, but none of the 34 6q15-deleted foci showed areas of ERG positivity (p = 0.022). In conclusion, our data suggest that ERG-fusion can precede 6q15 deletion, but not vice versa. The complete absence of ERG-positive tumor areas in 6q15-deleted tumor foci further suggest that the functional consequences of 6q15 deletions may prevent the development of TMPRSS2:ERG fusions. Impact Journals LLC 2015-12-14 /pmc/articles/PMC4826178/ /pubmed/26684029 http://dx.doi.org/10.18632/oncotarget.6597 Text en Copyright: © 2016 Kluth et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Kluth, Martina
Meyer, David
Krohn, Antje
Freudenthaler, Fabian
Bauer, Melanie
Salomon, Georg
Heinzer, Hans
Michl, Uwe
Steurer, Stefan
Simon, Ronald
Sauter, Guido
Schlomm, Thorsten
Minner, Sarah
Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer
title Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer
title_full Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer
title_fullStr Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer
title_full_unstemmed Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer
title_short Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer
title_sort heterogeneity and chronology of 6q15 deletion and erg-fusion in prostate cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826178/
https://www.ncbi.nlm.nih.gov/pubmed/26684029
http://dx.doi.org/10.18632/oncotarget.6597
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