Division of Molecular Genetics

Our laboratory applies oncogenomic approaches for the elucidation of pathomechanisms of tumor etiology and progression as a basis for novel treatment strategies and for the identification of prognostic and predictive genes and gene signatures. To this aim, we perform large screens using comprehensive molecular profiling technologies revealing tumor cell alterations at the level of the genome, transcriptome, methylome and chromatin. Integration of such data sets with clinical data allows us to identify candidate genes, which we subsequently test for their i) possible role in tumor pathophysiology, ii) potential as targets for novel therapy-strategies, iii) prognostic value to stratify patient subgroups for risk-adapted therapy regimens and iv) potential to predict therapy response or resistance in cancer patients. Within the last 5 years, we have greatly contributed to novel tumor sub-classification schemes that allow for stratification of cancer patients for different therapy regimens on the basis of molecular tumor profiles. This is particularly true for pediatric and adult brain tumors, breast cancer and low-grade B-cell lymphoma. Through the identification of pathogenically relevant genes, we have identified candidate targets for the development of novel therapies, in particular in leukemia and glioma. Through the functional characterization of candidate genes, we also developed pre-clinical models for the testing of novel therapies.

FUTURE OUTLOOK:
We apply molecular profiling of cancer cell populations on the level of the genome, methylome, transcriptome, chromatin and proteome to identify the entire spectrum of alterations that may occur in a given tumor entity and to assess their clinical relevance. This is done with special focus on brain tumors and non-Hodgkin lymphomas, but is also extended to other tumor entities such as breast cancer. The contribution of the tumor-microenvironment to carcinogenesis has become a further focus, in particular with regard to non-Hodgkin lymphoma. Furthermore, we implement a strategy for the establishment of cancer genome sequencing in clinical diagnostic settings, by sequencing of the entire exome, genome, methylome or transcriptome of respective patient cohorts. Candidate genes, for which we established a pathogenic role in carcinogenesis, are tested in pre-clinical in vitro and in vivo models using known inhibitors. More recently, we established and developed novel approaches for the generation of mouse models by somatic gene transfer that allow testing of gain-of-function and loss-offunction candidate genes in an unprecedented rapid mode also including CRISPR/Cas technologies. We also complement these studies by the isolation of novel inhibitors, exploiting the DKFZ/EMBL core facility for the screening of small molecular libraries as well as the screening of biological extracts through dedicated scientific collaborations. We also greatly contribute to the establishment of novel clinical umbrella trials that aim at treating relapsed cancer patients on the basis of the identified novel targets inferring novel treatment options.