PROJECT 1 – PROJECT SUMMARY Fibrolamellar hepatocellular carcinoma (FLHCC) is an often-lethal disease affecting primarily children and young adults. The poor prognosis is exacerbated by the lack of both existing diagnostic tests and systemic therapy. We have recently demonstrated that there is a single, consistent deletion in one copy of chromosome 19 in FLHCC patients that results in a chimeric gene. This chimera encodes a fusion protein, a constitutively active catalytic subunit of protein kinase A. This project has two aims: (1) develop the first diagnostic tests for this cancer and (2) develop the first blockers for the driver for this cancer.