Summary

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.
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-of function candidate genes in an unprecedented rapid mode also including CRISPR/Cas technologies. Functional analyses are performed with special focus on tumor microenvironment and tumor metabolism. Strong emphasis is also put on uncovering processes that cause genomic instability and therefore drive tumor etiology and/or progression.