la Rosa Alfredo Harb-De, Manoharan Meenakkshy, Goolam Ahmed Saeed
Department of Urology, University of Miami Miller School of Medicine, P.O Box 016960 (M814), Miami, FL USA.
Washington University in St. Louis of Medicine, St. Louis, MO 63130 USA.
Indian J Surg Oncol. 2017 Jun;8(2):169-174. doi: 10.1007/s13193-016-0593-2. Epub 2017 Jan 13.
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.
睾丸生殖细胞肿瘤(GCTs)分为精原细胞瘤(SGCTs)和非精原性睾丸生殖细胞肿瘤(NSGCTs)。血清肿瘤标志物(STMs)在睾丸癌中起着重要作用,因为它们为诊断、分期和复发检测提供有用信息。尽管如此,仍需要额外的肿瘤标志物用于早期诊断和治疗选择,以提高睾丸癌血清学诊断的特异性。表观遗传学被定义为基因表达的遗传性变化,这些变化未编码在DNA结构中。表观遗传变化包括DNA甲基化、组蛋白修饰和微小RNA(miRNA)调控。正是通过表观遗传学研究,才可能建立睾丸癌的早期检测诊断方法和新的治疗策略。我们通过组合包括DNA甲基化、组蛋白修饰、微小RNA(miRNA)调控、表观遗传学和睾丸癌等搜索词,对PubMed中的英文医学文献进行了全面综述。DNA甲基化是研究最广泛的表观遗传修饰。它包括在核苷酸碱基上添加一个甲基基团。据报道,与NSGCT相比,SGCT的DNA甲基化水平降低。miRNA是调节转录后基因表达的小非编码RNA。有人提出,miRNA可能在GCT的发病机制中起作用。GCT患者的各种miRNA已显示出特定的表达模式。组蛋白是与盘绕的双链基因组DNA交织的蛋白质,形成一种称为核小体的结构。研究最广泛的组蛋白修饰包括乙酰化、甲基化和磷酸化。在所有类型的NSGCT中都发现了组蛋白甲基化。表观遗传学可能为睾丸GCT的诊断提供一种额外且有效的工具,包括预后信息,甚至可能使睾丸GCT患者能够接受靶向治疗。