Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer
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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.
in: ONCOTARGET, Jahrgang 7, Nr. 4, 26.01.2016, S. 3897-904.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer
AU - Kluth, Martina
AU - Meyer, David
AU - Krohn, Antje
AU - Freudenthaler, Fabian
AU - Bauer, Melanie
AU - Salomon, Georg
AU - Heinzer, Hans
AU - Michl, Uwe
AU - Steurer, Stefan
AU - Simon, Ronald
AU - Sauter, Guido
AU - Schlomm, Thorsten
AU - Minner, Sarah
PY - 2016/1/26
Y1 - 2016/1/26
N2 - 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.
AB - 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.
U2 - 10.18632/oncotarget.6597
DO - 10.18632/oncotarget.6597
M3 - SCORING: Journal article
C2 - 26684029
VL - 7
SP - 3897
EP - 3904
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 4
ER -