Description:
<jats:title>Abstract</jats:title>
<jats:p>Deletions at chromosome 6q15 belong one to the most frequent alterations in pros-tate cancer, and are linked to poor prognosis. Furthermore, there is a marked inverse relationship between 6q15 deletions and TMPRSS2:ERG fusions in prostate cancer. While heterogeneity may limit the applicability of diagnostic molecular markers, it is important to estimate in vivo heterogeneity and the sequel of appearance of potential prognostic markers. In case of one alteration developing after the other, we would expect a small area of cancer having both alterations within a larger area having only one (the first appearing) of these changes.</jats:p>
<jats:p>In this study, we used our heterogeneity tissue microarray approach as a surrogate method to determine in vivo heterogeneity of 6q15 deletions and TMPRSS2:ERG fusions. We constructed a heterogeneity TMA containing samples taken from 10 dif-ferent tumor containing tissue blocks of 189 prostate cancers. Each prostate con-tained 1 to 6 individual cancer foci allowing the molecular analysis of more than 350 tumor foci. 6q15 deletion was analyzed by fluorescence in situ hybridization and ERG expression by immunohistochemistry.</jats:p>
<jats:p>Only 6.6% of 334 ERG positive but 28.4% of 440 ERG negative TMA spots showed 6q15 deletions (p&lt;0.0001). A breakdown of these data to the level of tumor foci re-vealed 6q deletions in 34 tumor foci that were large enough to have at least 3 ana-lyzable TMA spots. The cohort included 42 tumor foci with a homogeneous ERG pos-itivity and 15 with a homogeneous 6q deletion. Remarkably, six of 42 homogeneously ERG positive tumor foci (14.3%) were focal 6q15-deleted, but none of 16 homogene-ous 6q15-deleted foci showed focal ERG positivity in the same tumor area (p=0.022).</jats:p>
<jats:p>In conclusion of our study, the complete absence of ERG positive tumor foci in 6q15-deleted cancers suggests that the functional consequences of 6q15 deletions may prevent the development of TMPRSS2:ERG fusions. However, the development of 6q15 deletions is independent of the ERG status.</jats:p>
<jats:p>Citation Format: Martina Kluth, Maria Christina Tsourlakis, David Meyer, Antje Krohn, Fabian Freudenthaler, Melanie Bauer, Georg Salomon, Hans Heinzer, Uwe Michl, Stefan Steurer, Ronald Simon, Guido Sauter, Thorsten Schlomm, Sarah Jane Pauline Minner. 6q15 deletion impede development of ERG fusion in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2216. doi:10.1158/1538-7445.AM2014-2216</jats:p>