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.
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 develop the first diagnostic tests and therapeutic treatments for fibrolamellar hepatocellular carcinoma.
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|Simon, Joel S; Botero, Sergio; Simon, Sanford M (2018) Sequencing the peripheral blood B and T cell repertoire - Quantifying robustness and limitations. J Immunol Methods 463:137-147|