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TET1 overexpression, DNA hypomethylation and aberrant expression of human endogenous retrovirus ERVWE1 in germ cell tumors
Benešová, Martina ; Trejbalová, Kateřina (advisor) ; Černá, Marie (referee) ; Reiniš, Milan (referee)
TGCTs are tumors of male germ cells. They comprise of seminomas and non-seminomas (embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma). GCT types differ in the stage of differentiation, from undifferentiated seminoma to more differentiated non-seminomas. In our studies, we aimed to characterize specific epigenetic features of GCT types that enable transcription derepression of the human endogenous retrovirus ERVWE1 in these tumors. We detected upregulated mRNA expression of TET1-3 dioxygenases in GCTs, especially of TET1 in seminomas. Moreover, seminomas showed low global levels of 5mC and 5hmC. TET1 knock-down in a seminoma-derived cell line resulted in a decreased amount of 5hmC and unchanged 5mC level. These results stress the dynamics of cytosine modifications, which has not been precisely described yet. Further, we observed high level of ERVWE1 transcript together with efficient RNA splicing in seminomas. Detected ERVWE1 transcription is independent of the expression of other examined endogenous retroviruses. ERVWE1 transcription derepression corresponds with the low global level of 5mC detected in seminomas, which involves extensive DNA hypomethylation of the ERVWE1 promoter. We propose the high TET1 dioxygenase expression as s marker of undifferentiated GCTs. Furthermore, we...
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