Deletion of 3p13 is a late event linked to progression of TMPRSS2:ERG fusion prostate cancer
| Autor: | Sohall Frogh, Thorsten Schlomm, Guido Sauter, Frank Jacobsen, Mohammad Hussein, Christina Möller-Koop, Sarah Minner, Billurvan Taskin, Andreas M. Lübke, Ronald Simon, Heinke Volta, Hartwig Huland, Hans Heinzer, Till S. Clauditz, Franziska Büscheck, Martina Kluth, Waldemar Wilczak, Markus Graefen, Andrea Hinsch, Maria Christina Tsourlakis |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Tissue microarray genetic structures medicine.diagnostic_test Biology medicine.disease TMPRSS2 03 medical and health sciences Prostate cancer 030104 developmental biology 0302 clinical medicine Oncology Homogeneous 030220 oncology & carcinogenesis medicine Cancer research Immunohistochemistry sense organs Erg Fluorescence in situ hybridization |
| Zdroj: | Cancer Management and Research. 10:5909-5917 |
| ISSN: | 1179-1322 |
| DOI: | 10.2147/cmar.s172637 |
| Popis: | Introduction Deletion of 3p13 is one of the most common alterations in prostate cancer preferentially occurring in tumors with TMPRSS2:ERG fusion. The cause for the striking association between 3p13 loss and ERG fusion is unknown. Methods Here, we made use of a preexisting heterogeneity prostate cancer tissue microarray including ten tissue spots from ten different tumor areas of 317 cancers to examine the spatial distribution of 3p13 deletions (determined by fluorescence in situ hybridization) in prostate cancer areas with and without ERG overexpression (determined by immunohistochemistry). Results 3p13 deletions were found in 61 of 299 (20.4%) and ERG positivity in 174 of 317 (54.9%) interpretable cancers. The likelihood of 3p13 loss was twice as high in ERG-positive cancers (39/152, 25.7%) than in ERG-negative cancers (17/124, 13.7%, P=0.010). At least three tissue spots were interpretable for 3p13 deletion status in 279 cancers: only these were used for heterogeneity assessment. Among these tumors, 58 (20.8%) had a 3p13 deletion and 221 (79.2%) were undeleted. The majority of 3p13-deleted cancers showed marked intratumoral heterogeneity. Areas with and without 3p13 loss were found in 50 (18%) of 279 cancers with three or more interpretable tissue spots, while only eight (3%) tumors had a homogeneous 3p13 loss. Comparison with ERG data revealed that ERG fusion usually precede 3p13 deletions. In total, 26 (66.7%) of 39 cancers with ERG and 3p13 alteration had only focal 3p13 deletions in an otherwise ERG-positive background. In contrast, none of the cancers showed a pattern that would be consistent with 3p13 deletion preceding ERG fusion. Conclusion Our study identifies 3p13 deletion as a highly heterogeneous alteration in prostate cancer preferentially developing at rather late stages of progression in TMPRSS2:ERG fusion-positive tumors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|