Proteomic Analysis of WNT Signaling and Metabolism of Fibrolamellar Hepatocellular Carcinoma

James Knox

OAI: oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1766

Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of liver cancer that primarily affects young adults and adolescents.Although characterized as a subvariant of hepatocellular carcinoma (HCC), we have shown it is distinct based on its pathogenesis, patient population and drug response.Our lab has identified a fusion gene DNAJB1::PRKACA that is found in almost all FLC tumor samples sequenced to date. The fusion gene when expressed in mouse liver is sufficient to generate FLC, and elimination of the fusion transcript kills human tumors. The fusion results from a ~400kb deletion on chromosome 19, beginning after the first exon ofDNAJB1, which encodes for a member of the DnaJ or Hrsp40 family of proteins, and ends before the second exon of PRKACA, the catalytic subunit of protein kinase A (PKAc). To date,there is no known successful treatment for this disease, and the five-year survival rate is around 40%.

Life Sciences