Fibrolamellar Hepatocellular Carcinoma: Mechanistic Distinction From Adult Hepatocellular Carcinoma

Fibrolamellar hepatocellular carcinoma (FL‐HCC) has historically been classified as a rare subtype of HCC. However, unlike “classic” HCC, it occurs in children and young adults without underlying liver disease. The recent discovery of a deletion mutation in all FL‐HCCs represented a major advancement in understanding the pathogenesis of this disease. This deletion results in the fusion of the genes encoding a heat shock protein (DNAJB1) and the catalytic subunit of protein kinase A (PKA, PRKACA), and overexpression of PRKACA and enhanced cAMP‐dependent PKA activity. This review summarizes recent advancements in FL‐HCC pathogenesis and characteristics of the HSP40‐PKA C protein.