Abstract
Abstract Differences in the global methylation pattern, i.e. hyper- as well as hypomethylation, are observed in cancer, including germ cell tumors (GCTs). Related to their precursor cells, GCT methylation status differs according to histology. We investigated the methylation pattern of normal fetal, infantile, and adult germ cells (n=103) and GCTs (n=251) by immunohistochemical staining for 5-mCytidine. The global methylation pattern of male germ cells changes from hypomethylation to hypermethylation, while female germ cells remain unmethylated at all stages. Undifferentiated GCTs (seminomas, carcinoma in situ and gonadoblastomas) are hypomethylated, whereas more differentiated GCTs (teratomas, yolk sac tumors, choriocarcinomas) show a higher degree of methylation. Embryonal carcinomas show an intermediate pattern. Resistance to cisplatin was assessed in the seminomatous cell line TCam-2 before and after demethylation using 5-azacytidine. Exposure to 5-azacytidine resulted in decreased resistance to cisplatin. Furthermore, after demethylation, the stem cell markers NANOG and POU5F1 (OCT3/4), as well as the germ cell specific marker VASA showed increased expression. Upon treatment with 5-azacytidine, TCam-2 cells were analyzed by high throughput methylation screen for changes in methylation sites of 14,000 genes. Among the genes revealing changes, interesting targets were identified, i.e. demethylation of KLF11, a putative tumor suppressor gene, and hypermethylation of CFLAR, a gene previously described in treatment resistance in GCTs. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-67.
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