Alterations of global histone H4K20 methylation during prostate carcinogenesis

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.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.H4K20 methylation levels constitute valuable markers for the dynamic process of prostate cancer carcinogenesis.Valuable insight into epigenetics of prostate cancer (PCA) carcinogenesis offers starting points for potential new markers of non-invasive cancer diagnosis, progression and prognosis [1]. Recent observations suggest that changes in DNA methylation or gene silencing by CpG island promoter hypermethylation are not isolated events in inactivation of tumor suppressor genes, but accompanied by alterations of global histone modification levels as common hallmarks of PCA cells [2]. Histones are subject to a variety of posttranslational modifications (e.g. methylation, acetylation) on the N-terminal tail. These modifications function either by disrupting chromatin contacts or by affecting the recruitment of various proteins to the chromatin and thereby regulating transcription [3]. Histone lysine methylation results in transcriptional activation or repression, depending on the modified lysine site, an