Increased expression of Tet-1 associated with 5-methylcytosine hydroxylation in seminoma

Konference: 2013 The 9th Symposium & Workshop on Molecular Pathology and Histo(cyto)chemistry

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: Invited guests

Číslo abstraktu: 07

Autoři: Kateřina Trejbalová; Martina Dobšová; Mgr. Magda Matoušková; Doc. MUDr. Zdeňka Vernerová, CSc.; RNDr. Jiří Hejnar, CSc.

DNA methylation at the 5 position of cytosine (5-mC) followed by guanine is a key epigenetic mark that is often aberrantly increased or decreased in cancer and other pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the activity of ten-eleven translocation (TET) family of DNA hydroxylases and further demethylated by various cellular processes. Although this active demethylation of DNA normally occurs in early mammalian development, several recent reports describe the loss of TET expression and 5-hmC in glioblastoma, melanoma, and colon carcinoma. These changes might be a part of so called methylator phenotypes and can be of diagnostic and prognostic importance. Here we show an unusual TET-1 overexpression in seminomas and mixed germinal tumors with seminoma components. The increased proportion of 5-hmC at the expense of 5-mC will be demonstrated at the wholegenome level as well as at particular gene promoters. We show that isocitrate dehydrogenase 2 (ID H2) gene is not inactivated by mutations and produces normal levels of alpha-ketoglutarate necessary for the TET family enzymes. Thus, our study reveals an interesting epigenetic and epigenomic phenotype in seminoma.

Datum přednesení příspěvku: 26. 4. 2013