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, When cAMP bounds to the regulatory subunits, the catalytic subunits become active. Alpha subunits of stimulatory G-protein (G?s, encoded by GNAS) activates the adenylyl cyclase, leading to production of cAMP and subsequent activation of PKA. Over-activation of PKA in liver tumors is associated with fibrolamellar features in 4 settings: (i) the DNAJB1-PRKACA fusion in FLC, (ii) inactivating mutations in PRKAR1A in rare FLC developed in Carney complex patients, (iii) activating mutations in GNAS in rare hepatocellular adenomas characterized by fibrolamellar-like patterns and (iv)

, Supp Figure 5: mRNA expression of lineage and differentiation markers mRNA expression of markers of hepatocytes, cholangiocytes (KRT7), pancreas, neuroendocrine markers, neural guidance molecules and receptors located on the membrane of the neurons assessed by RNAseq in normal liver (n=3), non-BAP1/fusPRKACA (n=118), BAP1 (n=18) and fusPRKACA (n=15) tumors