TY - JOUR
T1 - Differential expression of DNA methyltransferases and demethylases among the various testicular germ cell tumor subtypes
AU - Lobo, João
AU - Guimarães, Rita
AU - Miranda-Gonçalves, Vera
AU - Monteiro-Reis, Sara
AU - Cantante, Mariana
AU - Antunes, Luís
AU - Braga, Isaac
AU - Maurício, Joaquina
AU - Looijenga, Leendert H.J.
AU - Jerónimo, Carmen
AU - Henrique, Rui
N1 - Publisher Copyright:
© 2020 Future Medicine Ltd.
PY - 2020/9
Y1 - 2020/9
N2 - Aim: Characterize DNA methyltransferases/demethylases expression in testicular germ cell tumors (TGCTs). Methods: In silico 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). Results: DNMT3A, DNMT3B and TET2 were the most differentially expressed between seminomas (SEs) and nonseminomas (NSs). DNMT3B was significantly overexpressed in NS-related cell lines, and the opposite was found for TET2. Significantly higher DNMT3A/B mRNA expression was observed in NS, indicating a role for de novo 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. Conclusion: DNA-modifying enzymes are differentially expressed between TGCT subtypes, influencing reprogramming and differentiation.
AB - Aim: Characterize DNA methyltransferases/demethylases expression in testicular germ cell tumors (TGCTs). Methods: In silico 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). Results: DNMT3A, DNMT3B and TET2 were the most differentially expressed between seminomas (SEs) and nonseminomas (NSs). DNMT3B was significantly overexpressed in NS-related cell lines, and the opposite was found for TET2. Significantly higher DNMT3A/B mRNA expression was observed in NS, indicating a role for de novo 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. Conclusion: DNA-modifying enzymes are differentially expressed between TGCT subtypes, influencing reprogramming and differentiation.
KW - demethylases
KW - epigenetics
KW - methyltransferases
KW - nonseminoma
KW - seminoma
KW - testicular germ cell tumors
UR - http://www.scopus.com/inward/record.url?scp=85092120015&partnerID=8YFLogxK
U2 - 10.2217/epi-2020-0066
DO - 10.2217/epi-2020-0066
M3 - Article
C2 - 32957806
VL - 12
SP - 1579
EP - 1592
JO - Epigenomics
JF - Epigenomics
SN - 1750-1911
IS - 18
ER -