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The remarkable developments in molecular high throughput technologies significantly enhanced our knowledge about tumor biology, transforming mutations, epigenetic changes and altered cellular functions of cancer cells. These findings fostered new strategies to identify molecular markers for diagnostic, prognostic and predictive purposes.
In parallel, there has been an enormous development of novel imaging technologies leading to a significantly increased resolution for molecular imaging in vivo. Further improvements of molecular imaging can be anticipated and will greatly enhance our ability to diagnose and monitor malignant disease. Moreover, results obtained by cancer genome expression analysis will have an impact on strategies in molecular imaging.
Most importantly, the rapid translation of these new opportunities will greatly benefit from well established tissue banks such as the histopathological reference centers and the Laboratory for Translational Genomics within the CIO Köln-Bonn.

Genomics Technologies

Under the leadership of P. Nürnberg and M. Nöthen, the Cologne Center for Genomics (CCG) and the Dept. of Genomics at the Life&Brain Center in Bonn were established to foster the analysis of complex diseases as well as translational research programs (8.4.4). Both centers closely cooperate within the National Genome Research Network (NGFN) as members of the National Genotyping Platform. These centers provide the scientific and clinical community with the whole spectrum of SNP typing technologies ranging from single-plex to highly multiplexed methods, including the latest array-based platforms from Affymetrix and Illumina. At the CCG, ultra-deep sequencing using the GS 20 from Roche was established in 2007.

Tumor Reference Center

In Bonn nationwide tumor reference centers for brain tumors (T. Pietsch), prostate carcinomas, hereditary breast, ovary and colorectal cancers (R. Büttner, N. Wernert) and for sarcomas (E. Wardelmann, R. Büttner) systematically collect and characterize tumors on a molecular level for diagnostic and predictive purposes. In Köln, the national study groups on chronic lymphocytic leukemia (CLL) (P. Staib, M. Hallek) and Hodgkin’s disease (D. Re, A. Engert) have established tumor banks for a similar purpose.

Genetic Alterations in Cancer

Several groups in both Bonn and Köln are working on specific genetic alterations that might be used for prognostic purposes. The group of P. Staib and K.A. Kreuzer is searching for new molecular markers for the monitoring of B cell chronic lymphocytic leukemia. Similar projects have been initiated for acute leukemias (I. Gütgemann), lung cancer (J. Brabender), colon cancer (D. Vallboehmer), and gastric cancer (S. Mönig). Within a national network for neuroblastoma research (as part of the NGFN), array-based comparative genomic hybridization (aCGH) (R. Spitz) and gene expression profiling (M. Fischer) are applied to identify novel genetic alterations in this type of tumor. R. Büttner initiated an application to the Deutsche Krebshilfe for a national network for sarcoma research aimed at identifying predictive genetic markers within well-characterized patient cohorts.

The Clinical Genomics Group Cologne (CGGC, co-ordinator J. Schultze) is conducting a pilot genomic screen in the peripheral blood of more than 400 cancer patients to identify novel therapeutic targets and biomarkers. The identification of novel molecular markers is also a major topic of the groups of A. Becker (epilepsy associated brain tumors), A. Waha (genome-wide methylation screens) and J. Schultze (TGFß inhibitors). H.C. Hennies identifies molecular signatures of cancers associated with genetic skin disorders.

Imaging

Imaging as an important diagnostic tool in cancer treatment and research is a major focus in both Köln and Bonn. C. Kuhl is developing new imaging strategies for early diagnosis of malignant solid tumors, with an emphasis on breast and prostate cancer. H. Schild is developing a clinical application of high resolution MRT, and is working together with H.J. Biersack on new tracers for PET-CT to detect small tumors and metastases. A. Jacobs is leading the imaging group at the MPI for Neurological Research and heading the EU-funded Network of Excellence “Diagnostic Molecular Imaging in Neuroscience and Cardiovasular Disease” A. Gossmann is working on non-invasive monitoring strategies with dynamic MR imaging (dMRi) in the context of convection enhanced delivery (CED) e.g. of intratumoral application of mitoxantrone (MXN). DMRi is also used by C. Bangard in pre-clinical models to monitor the effect of anti-angiogenic therapies.

Translational Clinical Trials
The working groups of Professor Jürgen Wolf and  Associate Professor Roman Thomas (University Hospital Köln) and Dr Roland Ullrich (Max Planck Institute for Neuroscience, Köln) as well as Professor Reinhard Bűttner (Pathology, University Hospital Bonn) have, in close cooperation, established a translational study platform for the integration of genomic analysis and methods of molecular imaging (FDG-, FLT-PET, DCE-MRI). The project  specifically evaluates targeted drugs for the treatment of bronchial carcinoma with the objective to develop predictive biomarkers for the individualised application of these substances.  

Research Teams for Genomics, Molecular Markers and Imaging