Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary tumor in children, adolescents and young adults. The primary tumor is initiated and driven by a single alteration in the DNA: A deletion of ~400kb that results in a fusion gene between the heat shock co-chaperone DNAJB1 and the catalytic subunit of protein kinase A, PRKACA. If the tumor is limited to the liver, then surgery is the accepted therapy. However, if the tumor has metastasized, there is no accepted therapy. Project 1 of the center will determine how the fusion oncoprotein leads to pathogenesis. Specifically what is different about the fusion oncoprotein that causes changes in the cell. The fusion oncoprotein that drives this childhood cancer is a kinase and this project will determine the direct targets for this enzyme as well as explore how changes in the structure of the fusion oncoprotein may affect its localization and its targets.