Testicular cancer is the most common solid tumor affecting young males. Most testicular cancers are testicular germ cell tumors (TGCTs), which are divided into seminomas (SGCTs) and non-seminomatous testicular germ cell tumors (NSGCTs). During their development, primordial germ cells (PGCs) undergo epigenetic modifications and any disturbances in their pattern might lead to cancer development. The present study provides a comprehensive review of the epigenetic mechanisms–DNA methylation, histone post-translational modifications, bivalent marks, non-coding RNA–associated with TGCT susceptibility, initiation, progression and response to chemotherapy. Another important purpose of this review is to highlight the recent investigations regarding the identification and development of epigenetic biomarkers as powerful tools for the diagnostic, prognostic and especially for epigenetic-based therapy.
Summary The process of cytodifferentiation in spermatogenesis is governed by a unique genetic and molecular programme. In this context, accurate ‘tuning’ of the regulatory mechanisms involved in germ cells differentiation is required, as any error could have dramatic consequences on species survival and maintenance. To study the processes that govern the spatial–temporal expression of genes, as well as analyse transmission of epigenetic information to descendants, an integrated approach of genetics, biochemistry and cytology data is necessary. As information in the literature on interplay between DNA methylation and histone H3 lysine 4 trimethylation (H3K4me3) in the advanced stages of murine spermatogenesis is still scarce, we investigated the effect of a DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine, at the cytological level using immunocytochemistry methodology. Our results revealed a particular distribution of H3K4me3 during sperm cell differentiation and highlighted an important role for regulation of DNA methylation in controlling histone methylation and chromatin remodelling during spermatogenesis.
During the last decades, male urogenital cancers (including prostate, renal, bladder and testicular cancers) have become one of the most frequently encountered malignancies affecting all ages. While their great variety has promoted the development of various diagnosis, treatment and monitoring strategies, some aspects such as the common involvement of epigenetic mechanisms are still not elucidated. Epigenetic processes have come into the spotlight in the past years as important players in the initiation and progression of tumors, leading to a plethora of studies highlighting their potential as biomarkers for diagnosis, staging, prognosis, and even as therapeutic targets. Thus, fostering research on the various epigenetic mechanisms and their roles in cancer remains a priority for the scientific community. This review focuses on one of the main epigenetic mechanisms, namely, the methylation of the histone H3 at various sites and its involvement in male urogenital cancers. This histone modification presents a great interest due to its modulatory effect on gene expression, leading either to activation (e.g., H3K4me3, H3K36me3) or repression (e.g., H3K27me3, H3K9me3). In the last few years, growing evidence has demonstrated the aberrant expression of enzymes that methylate/demethylate histone H3 in cancer and inflammatory diseases, that might contribute to the initiation and progression of such disorders. We highlight how these particular epigenetic modifications are emerging as potential diagnostic and prognostic biomarkers or targets for the treatment of urogenital cancers.
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