Mutational signatures analysis is routinely applied in cancer genomic studies to identify endogenous and exogenous sources of mutagenesis operating in cancer. DNA damage induced by the exposure of tobacco carcinogens is, among others, one the most prominent mutational signature identified in treatment naïve SCLC samples. In B06, M. Cartolano will provide a detailed characterization of the mutational signatures operating in SCLC described in the context of the cell of origin and exposure to cigarette smoke. Given that the relevance of these mutational processes for the evolution of the SCLC phenotype is largely unexplored, M.Cartolano will then explore how evolving mutational processes correlate with the acquisition of resistance mechanisms to therapy and metastatic spreading.