Differential expression of DNA methyltransferases and demethylases among the various testicular germ cell tumor subtypes

• Published in: Epigenomics Vol. 12; no. 18; pp. 1579 - 1592
• Main Authors: Lobo, João, Guimarães, Rita, Miranda-Gonçalves, Vera, Monteiro-Reis, Sara, Cantante, Mariana, Antunes, Luís, Braga, Isaac, Maurício, Joaquina, Looijenga, Leendert Hj, Jerónimo, Carmen, Henrique, Rui
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01-09-2020
• Subjects: Adolescent; Adult; Biotechnology; Cell Line, Tumor; Computer Simulation; demethylases; Demethylation; Deoxyribonucleic acid; Dioxygenases; DNA; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNA methylation; DNA Methyltransferase 3A; DNA Methyltransferase 3B; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Enzymes; Epigenetics; Gene expression; Humans; Immunohistochemistry; Male; methyltransferases; Middle Aged; Neoplasms, Germ Cell and Embryonal - classification; Neoplasms, Germ Cell and Embryonal - enzymology; Neoplasms, Germ Cell and Embryonal - genetics; nonseminoma; Polymerase chain reaction; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; RNA, Messenger - metabolism; Seminoma; Stem cells; Testes; testicular germ cell tumors; Testicular Neoplasms - classification; Testicular Neoplasms - enzymology; Testicular Neoplasms - genetics; Transcription; Tumors; Young Adult; Netherlands; methyltransferases; seminoma; nonseminoma; demethylases; epigenetics; testicular germ cell tumors
• ISSN: 1750-1911; 1750-192X
• DOI: 10.2217/epi-2020-0066

Characterize DNA methyltransferases/demethylases expression in testicular germ cell tumors (TGCTs).
analysis of TCGA database, assessment of transcript levels of most relevant enzymes in four TGCT cell lines and validation in patient cohort (real-time quantitative polymerase chain reaction; immunohistochemistry).
,
and
were the most differentially expressed between seminomas (SEs) and nonseminomas (NSs).
was significantly overexpressed in NS-related cell lines, and the opposite was found for
. Significantly higher
mRNA expression was observed in NS, indicating a role for
methylation in reprogramming. Significantly higher TET2 protein expression was observed in SEs, suggesting active demethylation contributes for SE hypomethylated state. More differentiated histologies disclosed distinct expression patterns.
DNA-modifying enzymes are differentially expressed between TGCT subtypes, influencing reprogramming and differentiation.