My laboratory has employed gene-targeting technology to create mouse models of human lung cancer to study tumor progression and metastasis. Our gene-expression analyses of primary lung tumors, metastases and cell lines have uncovered a metastasis-associated gene expression signature. Integration of these datasets with human tumor data are providing insights into the underlying mechanisms of metastasis. Several tumors and cell lines from these models have been subjected by us to whole-exome and whole-genome DNA sequencing as well. These data are providing us with an increasingly complete view of tumor evolution leading to metastatic dissemination in these model systems and in human lung cancer.