Gene rearrangement and expression of PRKACA and PRKACB governs morpho-biology of pancreatobiliary oncocytic neoplasms. (PubMed, Mod Pathol)
We analyzed PRKACA/B fusion genes including ATP1B1-PRKACA, DNAJB1-PRKACA, and ATP1B1-PRKACB by reverse transcription PCR (RT-PCR); mRNA expression of fusion genes and non-rearranged PRKACA/B genes by quantitative RT-PCR; mutations in KRAS, BRAF, and GNAS by targeted sequencing or droplet digital PCR; and the expression of cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) and beta (PRKACB), phosphorylated-CREB, and aberrations of p16, p53, SMAD4, STK11, and β-catenin by immunohistochemistry...In conclusion, PRKACA/B fusion genes are not only the characteristic drivers of IOPNs, but also play a crucial role in the development of subclonal oncocytic neoplasms. Moreover, oncocytic morphology is strongly associated with upregulation of PRKACA/B, which may provide clues for potential therapeutic options.