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Clinical Cooperation Unit Neuropathology

Prof. Dr. Andreas von Deimling

Example for development of a diagnostic tool. Our antibody H09 specifically binds to IDH1 protein with the R132H mutation. All tumor cells impose in strong brown color while normal brain tissue is stained blue and grey.
© dkfz.de

Our research focuses on the molecular genetics of pediatric and adult tumors of the central nervous system. Most of our projects deal with the precise characterization of these tumors and on developing tools for the diagnostic community. Due to this focus we are centrally involved in defining the parameters for the WHO brain tumor classification system. This also places us in the position to demonstrate the feasibility of modern technology for routine diagnostic use.

Prof. A. Korshunov examines pediatric brain tumors in close cooperation with other groups from the DKFZ, with a focus on medulloblastomas, pilocytic astrocytomas and ependymomas. We are participating in the International Cancer Genome Consortium (ICGC). Drs. D. Capper, F. Sahm, C. Kölsche, Dr. Schrimpf and Dr. Stichel are developing novel tools and algorithms for molecularly based diagnosis of human brain tumors and sarcomas. These projects are based on methylome analysis and next generation sequencing approaches. There is a very close cooperation with other DKFZ based institutions such as the groups headed by Prof. S. Pfister, Prof. M. Platten and Prof. W. Wick. Dr. S. Pusch from our group is conducting research on the function of mutated IDH1 and CIC employing mouse models. The tumor syndrome neurofibromatosis type 1 is caused by mutations of the NF1 gene, which encodes neurofibromin. Many biological features of neurofibromin are mediated by its RasGAP activity. However, additional functions have been suggested. A group headed by Dr. D. Reuss is uncovering alternative pathways of neurofibromin to inhibit tumor cell growth. Our molecular diagnostic program serves multiple clinical studies by providing data such as mutational status of tumor suppressor genes or oncogenes. Our partners in pediatric and adult Neurooncology compare these data with clinical parameters.

FUTURE OUTLOOK
We will contribute to genomic analyses of medulloblastoma and pilocytic astrocytoma within the ICGC: Acquisition of high-quality tumor and matched germline samples according to ICGC guidelines, histopathological assessment, acquisition of clinical data and follow-up information, and molecular characterization of samples using previously proposed diagnostic and prognostic markers. In cooperation with DKFZ partners, we are developing diagnostic tools for neuropathology as well as for pathology. We expect to produce a highly accurate methylation based classification tool for brain tumors and sarcomas in short time. In our molecular diagnostic program, we are attempting to meet the growing demand from our clinical partners within the DKFZ as well as from multicenter studies. We expect an increasing demand for molecular analyses prior to entry of patients into clinical studies. We are prepared to adapt our molecular diagnostic assays to the needs of individual study protocols.

Contact

Prof. Dr. Andreas von Deimling
Neuropathology (B300)

Deutsches Krebsforschungszentrum und Abt. für Neuropathologie, Institut für Pathologie
Im Neuenheimer Feld 224
69120 Heidelberg

Tel: +49 6221 56 4650
E-Mail: andreas.vondeimling@dkfz.de

Selected Publications

  • Rohrich M, Koelsche C, Schrimpf D, Capper D, Sahm F, Kratz A, Reuss J, Hovestadt V, Jones DT, Bewerunge-Hudler M, Becker A, Weis J, Mawrin C, Mittelbronn M, Perry A, Mautner VF, Mechtersheimer G, Hartmann C, Okuducu AF, Arp M, Seiz-Rosenhagen M, Hanggi D, Heim S, Paulus W, Schittenhelm J, Ahmadi R, Herold-Mende C, Unterberg A, Pfister SM, von Deimling A, Reuss DE: Methylation-based classification of benign and malignant peripheral nerve sheath tumors. Acta Neuropathol Epub ahead of print.
  • Sahm F, Schrimpf D, Olar A, Koelsche C, Reuss D, Bissel J, Kratz A, Capper D, Schefzyk S, Hielscher T, Wang Q, Sulman EP, Adeberg S, Koch A, Okuducu AF, Brehmer S, Schittenhelm J, Becker A, Brokinkel B, Schmidt M, Ull T, Gousias K, Friederike A, Lamszus KK, Debus J, Mawrin C, Kim YJ, Simon M, Ketter R, Paulus W, Aldape KD, Herold-Mende C, von Deimling A: TERT Promoter Mutations and Risk of Recurrence in Meningioma. J Natl Cancer Inst 108 (5), Epub ahead of print.
  • Korshunov A, Ryzhova M, Hovestadt V, Bender S, Sturm D, Capper D, Meyer J, Schrimpf D, Kool M, Northcott PA, Zheludkova O, Milde T, Witt O, Kulozik AE, Reifenberger G, Jabado N, Perry A, Lichter P, von Deimling A, Pfister SM, Jones DT: Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers. Acta Neuropathol 2015.
  • Reuss DE, Sahm F, Schrimpf D, Wiestler B, Capper D, Koelsche C, Schweizer L, Korshunov A, Jones DT, Hovestadt V, Mittelbronn M, Schittenhelm J, Herold-Mende C, Unterberg A, Platten M, Weller M, Wick W, Pfister SM, von Deimling A: ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated" diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol 129 (1), 133-46, 2015.
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