Analysis of TET expression/activity and 5mC oxidation during normal and malignant germ cell development.

During mammalian development the fertilized zygote and primordial germ cells lose their DNA methylation within one cell cycle leading to the concept of active DNA demethylation. Recent studies identified the TET hydroxylases as key enzymes responsible for active DNA demethylation, catalyzing the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine. Further oxidation and activation of the base excision repair mechanism leads to replacement of a modified cytosine by an unmodified one.

Transcription factor TFAP2C regulates major programs required for murine fetal germ cell maintenance and haploinsufficiency predisposes to teratomas in male mice.

Maintenance and maturation of primordial germ cells is controlled by complex genetic and epigenetic cascades, and disturbances in this network lead to either infertility or malignant aberration. Transcription factor TFAP2C has been described to be essential for primordial germ cell maintenance and to be upregulated in several human germ cell cancers. Using global gene expression profiling, we identified genes deregulated upon loss of Tfap2c in embryonic stem cells and primordial germ cell-like cells.

Establishment of a versatile seminoma model indicates cellular plasticity of germ cell tumor cells.

In western countries, 60% of all malignancies diagnosed in men between 17-45 years of age are germ cell tumors (GCT). GCT arise from the common precursor lesion carcinoma in situ, which transforms within an average of 9 years into invasive Type-II GCTs. Seminomas are considered to be the default developmental pathway of carcinoma in situ cells and the seminoma-like cell line TCam-2 has been used to study seminoma biology in vitro.