Current Concepts of Epigenetics in Testicular Cancer

Abstract

Testicular germ cell tumors (GCTs) are characterized into seminomas (SGCTs) and non-seminomatous testicular germ cell tumors (NSGCTs). Serum tumor markers (STMs) play an important role in testicular cancer as they provide useful information for diagnosis, staging, and detection of recurrence. Nonetheless, additional tumor markers for early diagnosis and therapeutic options are required to enhance specificity of serological diagnosis of testes cancers. Epigenetics is defined as inherited changes in gene expression that are not encoded in the DNA structure. Epigenetic changes include DNA methylation, histone modifications, and microRNA (miRNA) regulation. It is through the study of epigenetics that diagnostic methods for early detection and novel therapeutic strategies may be established for testicular cancer. We performed a comprehensive review of the English medical literature in PubMed by combining search terms including DNA methylation, histone modifications, microRNA (miRNA) regulation, epigenetics, and testicular cancer. DNA methylation is the most extensively studied epigenetic modification. It consists of the addition of a methyl group to nucleotide bases. It has been reported that SGCT contain reduced levels of DNA methylation compared to NSGCT. MiRNAs are small non-coding RNAs that regulate posttranscriptional gene expression. It has been suggested that miRNAs may play a role in the pathogenesis of GCT. Specific expression patterns have been displayed by various miRNAs in patients with GCT. Histones are proteins intertwined with coiled, double-stranded genomic DNA that form a structure known as a nucleosome. The most widely studied histone modifications include acetylation, methylation, and phosphorylation. Methylation of histone proteins has been found in all types of NSGCT. Epigenetics may offer an additional and effective tool in establishing a diagnosis of GCT of the testes, including prognostic information and perhaps enabling targeted treatment in patients with testicular GCT.

Keywords: DNA methylation; Histone modification; MicroRNA regulation; Testicular cancer.

Fig. 1

DNA methylation of CpG Island carried out by DNA methyl-transferase. a Attachment of transcription factor to DNA strand activates RNA polymerase inducing transcription and gene expression. b Methyl group prevents transcription factor attachment to DNA strand producing transcription inactivation and gene silencing