Moritz C. Oberstadt
Ernst Moritz Arndt University of Greifswald, Germany
Title: Epigenetics in glioma
Moritz C. Oberstadt has completed his Ph.D. at the age of 25 years from Ernst Moritz Arndt University Greifswald and works at the Center of Drug Absorption and Transport (C_DAT) in Greifswald, Germany. His research is focusing on Neuro-Oncology and he is the scientific coordinator of a German Neuro-Oncology Young Investigators Meeting.
Glioblastoma multiforme (GBM) is still the most frequent primary brain tumor in adults and is characterized by a highly aggressive phenotype. Despite advances in therapy, glioblastoma remains associated with poor prognosis and an overall survival time of about 1 year. A major underlying factor is resistance to different chemotherapeutics. Several chromosomal, genetic and epigenetic alterations were identified in GBM, but the clinical value of the most glioma-associated molecular aberrations remained unclear. However, a significant prognostic impact could be shown for the O6-methylguanine-DNA-methyltransferase (MGMT). The MGMT functions as a DNA repair enzyme, which repairs alkylating lesions of the DNA by removing mutagenic adducts from the O6 position of guanine, e.g. caused by the chemotherapeutic agent temozolomide. Hence, it confers drug resistance and the therapeutic response to alkylating agents is improved in tumor cells expressing low levels of MGMT. Furthermore, MGMT promoter methylation was demonstrated to result in decreased MGMT expression and correlates with a survival benefit in glioblastoma patients treated with alkylating chemotherapeutics such as temozolomide. Besides methylations histone modifications gain attention in glioma. Histone H3 modifications are involved in tumor cell proliferation and cell cycle progression. Further, histone modifications are connected to metabolic events in gliomas making them a pivotal therapeutic target in the future.