We are using cancer genome analysis to understand essential and clinically relevant biology about human cancer. DNA repair pathway aberrations significantly contribute to the genomic instability underlying cancerous development  and often determine the efficacy to a particular genotoxic therapy.   We used cancer genomics to identify a DNA aberration pattern that is associated with homologous recombination incompetence and human tumors displaying this DNA aberration profile are particularly sensitive to platinum based therapy. This method is used currently undergoing clinical testing to prioritize patients for platinum based therapy. In order to identify further clinically useful DNA aberration patterns, we have developed a next generation based model model system to systematically identify mutational signatures associated with defects in the various DNA repair pathways.