Characterization of tumor dormancy and the liver cancer stem cell, uncovered upon MYC inactivation in hepatocellular cancer

2056 We have previously shown that inactivation of the MYC oncogene is sufficient to induce sustained tumor regression of invasive liver cancers while uncovering the ability of the tumor cells to remain dormant. Upon MYC inactivation, tumor cells differentiate into normal cells including, hepatocytes and biliary cells, which form bile duct structures. Tumors rapidly lose expression of the tumor marker α-fetoprotein, increase expression of liver cell markers cytokeratin 8 and carcinoembryonic antigen, and in some cells the liver stem cell marker cytokeratin 19. Some of these differentiated tumor cells remained in a dormant state as long as MYC remains inactivated; however, MYC reactivation immediately restored their tumorigenic properties. We are investigating the clongenic ability of these tumor cells to regain their neoplastic properties and characterizing the molecular signature of these dormant cancer cells. Our results are consistent with the possibility that MYC induces hepatocellular carcinoma by malignantly transforming a liver stem cell.