Development of pre-clinical murine models for fibrolamellar hepatocellular carcinoma
He, A.; Coles, G. L.; Hartmann, G. H.; Le, V.; Mauch, B.; Xu, L.; Nguyen, T.; Hazard, F. K.; Sage, J.
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Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of cancer that affects primarily adolescents and young adults. FLC tumors are typically associated with an intrachromosomal deletion resulting in expression of a fusion protein between the chaperone DNAJ1B and the protein kinase PKA. FLC is challenging to study because of its rarity and limited pre-clinical models. Here we developed a novel transgenic mouse model of FLC. In this model, DNAJ1B-PKA expression in the liver of mouse embryos results in perinatal lethality associated with liver developmental defects, while DNAJ1B-PKA expression in the liver of adult mice initiates tumors resembling FLC at low penetrance. We sought to develop ex vivo cell models from these tumors but failed to establish long-term cell lines. New pre-clinical models of FLC will provide novel insights into the biology of this rare cancer and may help identify novel therapeutic strategies.
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