Tuberous sclerosis is a tumor predisposition syndrome that is due to mutations in the TSC1 and TSC2 genes.  Tuberous sclerosis patients often develop benign tumors in their lungs.  No one has looked carefully at involvement of these genes in lung cancer.  We have made preliminary observations that indicate that 1) loss of Tsc1 accelerates development of lung cancer in  a mouse model; and 2) the TSC genes appear to be involved by genetic analysis in about 25% of human lung cancers.  Here we propose to delineate the involvement of the TSC genes in lung cancer development in greater detail.  These patients may derive unique benefit from inhibitors of mTORC1, such as rapamycin.