Abstract : Tumor phenotype is influenced by multiple factors, including genetic and epigenetic alterations, tumor stroma, and systemic environment. Because of this complexity, it has been difficult to investigate the influence of normal cell phenotype on the behavior of its tumorigenic derivatives. In our previously published work we have shown that 10 BPLER cells were capable of forming tumors in mice and these BPLER tumors were metastatic to the lungs. In contrast, 100,000 HMLER cells derived from the same individuals were required to form tumors in mice and these tumors were non metastatic. The results of our studies during the first year of the grant confirm that genetic differences between BPLER and HMLER cells can not account for the phenotypic differences between these tumor types. The initial round of epigenetic studies with chromatin modifying drugs as well as Chip-on-chip analysis of H3K79me2 indicates that there is a significant difference between BPLER and HMLER cells derived from the intrinsic differences between their normal sell-of-origins.