Dataset Information

Deletion of 3p13 is a late event linked to progression of TMPRSS2:ERG fusion prostate cancer.

ABSTRACT: 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.

SUBMITTER: Kluth M

PROVIDER: S-EPMC6250107 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Deletion of 3p13 is a late event linked to progression of <i>TMPRSS2</i>:<i>ERG</i> fusion prostate cancer.

Kluth Martina M Volta Heinke H Hussein Mohammad M Taskin Billurvan B Frogh Sohall S Möller-Koop Christina C Büscheck Franziska F Jacobsen Frank F Tsourlakis Maria Christina MC Lübke Andreas M AM Hinsch Andrea A Clauditz Till T Graefen Markus M Heinzer Hans H Huland Hartwig H Minner Sarah S Sauter Guido G Wilczak Waldemar W Schlomm Thorsten T Simon Ronald R

Cancer management and research 20181119

<h4>Introduction</h4>Deletion of 3p13 is one of the most common alterations in prostate cancer preferentially occurring in tumors with <i>TMPRSS2:ERG</i> fusion. The cause for the striking association between 3p13 loss and <i>ERG</i> fusion is unknown.<h4>Methods</h4>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 fluores ...[more]

PMID: 30510458

Similar Datasets

Project description:The transmembrane protease serine 2:v‑ets erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion is common in prostate cancer, while its functional role is not fully understood. The present study aimed to investigate the significance of the TMPRSS2:ERG gene fusion in human prostate cancers using bioinformatics tools. Comprehensive alteration analysis of TMPRSS2 and ERG in 148 different human cancer studies was performed by cBioPortal, and the mRNA expression level of the ERG gene was evaluated using Oncomine analysis. Furthermore, lentiviral short hairpin (sh)RNA‑mediated knockdown of TMPRSS2:ERG was performed to study the impact of ERG silencing on cell proliferation and cell cycle distribution in prostate cancer cells. The results demonstrated that the TMPRSS2 and ERG genes were mostly altered in prostate cancer, and the most frequent alteration was gene fusion. Oncomine analysis demonstrated that the ERG gene was significantly upregulated in prostate clinical samples compared with the normal prostate gland in four independent datasets, and a positive association was observed between potassium inwardly‑rectifying channel subfamily J member 15, down syndrome critical region gene 4, potassium inwardly‑rectifying channel subfamily J member 6 and ERG gene expression. There were 272 mutations of the ERG gene identified in the cBioPortal database; among the mutations, 2 missense mutations (R367C and P401H) were regarded as functional mutations (functional impact score >1.938). Furthermore, the present study successfully knocked down ERG gene expression through a lentiviral‑mediated gene silencing approach in VCaP prostate cancer cells. The ERG mRNA and protein expression levels were both suppressed significantly, and a cell‑cycle arrest at G0/G1 phase was observed after ERG gene silencing. In conclusion, these bioinformatics analyses provide novel insights for TMPRSS2:ERG fusion gene study in prostate cancer. Target inhibition of ERG expression could significantly cause cell growth arrest in prostate cancer cells, which could be a potentially valuable target for prostate cancer treatment. However, the precise mechanism of these results remains unclear; therefore, further studies are required.

Dataset Information

Deletion of 3p13 is a late event linked to progression of TMPRSS2:ERG fusion prostate cancer.

Publications

Deletion of 3p13 is a late event linked to progression of <i>TMPRSS2</i>:<i>ERG</i> fusion prostate cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets