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Open Access Highly Accessed Research article

Alterations of global histone H4K20 methylation during prostate carcinogenesis

Turang E Behbahani1, Philip Kahl2, Johannes von der Gathen1, Lukas C Heukamp2, Claudia Baumann1, Ines Gütgemann3, Bernhard Walter4, Ferdinand Hofstädter5, Patrick J Bastian6, Alexander von Ruecker3, Stefan C Müller1, Sebastian Rogenhofer1 and Jörg Ellinger1*

Author Affiliations

1 Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Bonn, Germany

2 Institut für Pathologie der Universität zu Köln, Cologne, Germany

3 Institut für Pathologie, Universitätsklinikum Bonn, Bonn, Germany

4 Urologische Universitätsklinik, Universitätsklinikum Erlangen, Erlangen, Germany

5 Institut für Pathologie, Universitätsklinik Regensburg, Regensburg, Germany

6 Urologische Klinik und Poliklinik, Universitätsklinikum Großhadern, Munich, Germany

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BMC Urology 2012, 12:5  doi:10.1186/1471-2490-12-5

Published: 13 March 2012

Abstract

Background

Global histone modifications have been implicated in the progression of various tumour entities. Our study was designed to assess global methylation levels of histone 4 lysine 20 (H4K20me1-3) at different stages of prostate cancer (PCA) carcinogenesis.

Methods

Global H4K20 methylation levels were evaluated using a tissue microarray in patients with clinically localized PCA (n = 113), non-malignant prostate disease (n = 27), metastatic hormone-naive PCA (mPCA, n = 30) and castration-resistant PCA (CRPC, n = 34). Immunohistochemistry was performed to assess global levels of H4K20 methylation levels.

Results

Similar proportions of the normal, PCA, and mPCA prostate tissues showed strong H4K20me3 staining. CRPC tissue analysis showed the weakest immunostaining levels of H4K20me1 and H4K20me2, compared to other prostate tissues. H4K20me2 methylation levels indicated significant differences in examined tissues except for normal prostate versus PCA tissue. H4K20me1 differentiates CRPC from other prostate tissues. H4K20me1 was significantly correlated with lymph node metastases, and H4K20me2 showed a significant correlation with the Gleason score. However, H4K20 methylation levels failed to predict PSA recurrence after radical prostatectomy.

Conclusions

H4K20 methylation levels constitute valuable markers for the dynamic process of prostate cancer carcinogenesis.

Keywords:
Histone; Methylation; H4K20; Prostate cancer; Epigenetics