Epigenetic alterations of testicular germ cell tumours

Abstract

Purpose of review Testicular germ cell tumours (TGCTs) exhibit, in contrast to other cancer types, a relatively low mutational burden. However, numerous epigenetic alterations have been shown to impact TGCT. In this review, we summarize the most relevant findings of the past 2 years. Recent findings Recent studies focused on the functions of microRNAs and the impact of aberrant DNA methylation. Moreover, several epigenetic drugs with antineoplastic effects in TGCTs were identified. Summary Aberrant DNA methylation and differentially expressed microRNAs have an important effect on TGCT pathogenesis. Moreover, differential DNA methylation patterns were found to be specific for different TGCT subtypes. Various microRNAs, such as miR-371a-3p, were found to be highly sensitive and specific biomarkers for TGCT. The epigenetic drugs guadecitabine, animacroxam, and JQ1 showed promising effects on TGCT in preclinical in-vivo and in-vitro studies.

Hypermethylation and global remodelling of DNA methylation is associated with acquired cisplatin resistance in testicular germ cell tumours

“…A shift from gene body to promoter methylation is associated with decreased gene expression in resistant cells (combination of Group 1 and 3) and a shift from gene promoter to gene body CpG methylation is associated the inherent sensitivity of TGCTs [10][11][12][13]34]. TGCTs have distinct epigenetics, including distinct patterns of DNA methylation, and also have few somatic mutations suggesting that epigenetics may be a key driver of TGCT biology [35][36][37]. This has led to a popular recent proposal that DNA hypomethylation is a mechanism for TGCT cisplatin hypersensitivity and reciprocally DNA hypermethylation is a mechanism for cisplatin resistance [11,12,26].…”

Subgrouping testicular germ cell tumors based on immunotherapy and chemotherapy associated lncRNAs

“…At present, the pathogenesis of testicular tumors is not clear. Epidemiological analysis has found that various factors increase the chance of TGCT, including congenital factors such as cryptorchidism or undescended testes, Klinefelter syndrome, testicular feminization syndrome, acquired factors such as injury, infection, nutritional factors, and excessive use of exogenous estrogen by the mother during pregnancy [ 4 , 5 ].…”