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Molecular and translational neurooncology

Primary tumours of the central nervous system account for only 2-3% of all cancers but are responsible for 7% of the years of life lost from cancer before the age of 70. Epidemiological data estimate up to 5,000 brain tumour-related deaths per year in Germany. In children, CNS tumours are the second most common form of cancer after the leukemias and the most common cause of cancer-related death. Importantly, the incidence of brain tumours is increasing due to the ageing population.

However, there is still no curative therapy for malignant brain tumours, in particular glioblastoma, the most common primary brain tumour in adults. The development of more effective treatments will essentially rely on a better understanding of the molecular and cellular processes causing glioma development and progression. In addition, interdisciplinary translational studies are necessary to evaluate and validate novel diagnostic methods, including innovative molecular markers, and promising therapeutic approaches, including pathogenesis-based targeted strategies.

PIs

The investigation of molecular aberrations in gliomas is the primary research interest of  Guido Reifenberger at the Department of Neuropathology. His group has characterised novel molecular aberrations in brain tumours, some of which gained clinical significance as independent prognostic and prdeictive markers, such as combined losses of chromosal arms 1p and 19q in oligodendroglial tumors and promoter methylation of the MGMT gene in malignant gliomas, in particular glioblastomas.

Ongoing projects focus on the characterisation of aberrant signalling pathways in gliomas (Barbus, J Natl Cancer Inst 2011), the role of miRNAs and epigenetic changes in glioma pathogenesis (Malzkorn, Brain Pathol 2011), as well as the development and characterization of novel brain tumour models in mice (Liu, Genes Dev 2010).

The translation of novel laboratory findings into the molecular diagnostics of CNS tumours (Riemenschneider, Acta Neuropathol. 2010) is another research topic that is pursued in collaboration with the German Neurooncology Working Group (e.g. Glass, Ann Neurol 2011; Wick, J Clin Oncol 2009) and in multicentre collaborative projects, such as the German Glioma Network (www.gliomnetzwerk.de), the NGFNplus Brain Tumor Network, and the German ICGC PedBrain consortium (www.pedbraintumor.org). To facilitate translational research, the Department of Neuropathology has established a large CNS tumour tissue bank that is supported within the German Cancer Aid priority programme on tumour tissue banking (www.tumorgewebebanken.de).

Christiane B. Knobbe-Thomsen is a postdoctoral researcher from G. Reifenberger's group who is presently working in the laboratory of Prof. Tak Mak in Toronto, Canada. Her primary research interest is the development and characterization of novel genetically engineered mouse models for in vivo analyses of brain tumors and other cancers.

The research group of Gabriel Leprivier is interested in delineating the mechanisms supporting brain tumors adaptation to metabolic stress. His group is employing a wide range of molecular biology and cellular biology techniques to characterize the cellular components, including cell signaling molecules, which allow brain tumor to handle metabolic stress conditions and support their aggressiveness. This research may help uncovering novel therapeutic targets for these diseases.

The German Cancer Network (DKTK) junior research group "Pediatric Neuro-Oncogenomics" headed by Dr. Marc Remke focuses on proteogenomic approaches and high-throughput drug screening to improve treatment strategies for children and adults with brain tumors. With a long-standing interest and expertise in molecular brain tumor classification and biomarker development (Remke et al., JCO 2011 a/b; Morrissy*, Cavalli*, Remke* et al., Nat. Gen. 2017; Cavalli*, Remke* et al., Cancer Cell 2017), we identify novel long non-coding RNAs associated with molecular alterations (e.g. MYC amplification) or with clinicopathological features (e.g. poor prognosis). Our integrated genomics approach is complemented by well-established functional genomics techniques (Leprivier, Remke et al., Cell 2013; Vanner, Remke et al., Cancer Cell 2014) to determine the biological role and functional contribution of these candidates during brain tumor formation, maintenance, metastatic dissemination, and relapse.

Kai Stühler heads the Molecular Proteomics Laboratory of the Centre for Biological and Medical Research at HHU Düsseldorf. Concerning brain tumours, his primary research interest is placed on the identification of novel proteome-based markers for the improvement of glioma diagnostics (Grzendowski, Neuro Oncol 2010). For this purpose, his group uses large-scale 2D-DIGE and mass spectrometric techniques including modern label-free approaches to characterize the proteome of tumor tissue and plasma specimens from glioma patients.

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