Coordinator:    Prof. Dr. Roman Thomas
Institution: Universität zu Köln, Abteilung Translationale Genomik
Cancer is a disease of the genome. Somatic activation of proto-oncogenes and inactivation of tumor suppressor genes by gene copy number alterations, genomic rearrangements and subtle sequence alterations (mutations) such as point mutations and small insertions and deletions cause genetically encrypted alterations of intracellular signaling pathways that the tumor cell becomes ‘addicted’ to. This concept of oncogene addiction has been empowered by the notion that genetically activated oncogenes are ideal targets for anti-cancer drugs: EGFR-mutant lung tumors show sensitivity to the EGFR inhibitors gefitinib and erlotinib. This clinical success has sparked systematic efforts to comprehensively annotate the genomes of all major human cancer types. Given the role of mutations that activate proto-oncogenes in large fractions of cancers, our efforts were particularly focused on re-sequencing of coding exons of human genes. This cancer genome re-sequencing project has reached the dimension of all fully annotated genes in the human genome. Meanwhile, many human oncogene mutations are known as well as the functional and mechanistic consequences of these mutations for the genesis of tumors in cell systems and in patients.
The implementation of cancer genomics in clinical routine and the combination of molecular and clinical data now allow the personalized treatment of cancer patients with targeted cancer therapeutics. Furthermore we have developed methods that afford in-depth cellular and biochemical characterization of oncogenic lesions in cellular models. Within the NGFN-project Oncogene we were already able to translate first molecular findings into clinical therapeutic options for tumor patients.

Latest results can be found in detail in the descriptions of the subprojects.
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