Fibrolamellar hepatocellular carcinoma (FLHCC) is an often-lethal disease affecting primarily children and young adults. The poor prognosis stems from both the lack of sensitive non-invasive diagnostic tests and the lack of a targeted systemic therapy. We have recently demonstrated a single, consistent deletion in one copy of chromosome 19 of FLHCC patients that results in a chimeric gene. This encodes a chimeric protein comprised of the amino terminal portion of the heat shock protein DNAJB1 fused to the active catalytic subunit of protein kinase A. This project will determine if this chimera is sufficient for transforming cells. It will then determine the extent of cellular changes upon induction of the chimera and begin to elucidate the pathways and mechanisms for these changes.
Our ability to understand human cancers has been revolutionized the past two decades by the sequencing of the human genome and the ability to introduce altered genes into cells. This project builds upon this by using the study of a pediatric cancer to drive the study of critical genes in human hepatic cells. The project will identify those pathways that should be targets for therapy.
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