In B02, M. Peifer will generate a comprehensive portrait of the clonal evolution of SCLC. To this end, high-coverage genomic sequencing data, as well as single cell DNA sequencing data will be analyzed to determine: 1) the influence of the cell of origin on the evolution of SCLC and in comparison to other lung cancer subtypes, 2) establishing a temporal order of point mutations and copy number changes, and 3) reconstructing exact evolutionary trajectories under treatment. This project will be essential to determine the drug-naïve evolution of SCLC and how the evolutionary dynamics are altered under treatment. Differences under treatment pressure may help to identify possible resistance mechanisms.