Fibrolamellar Hepatocellular Carcinoma: Mechanistic Distinction From Adult Hepatocellular Carcinoma

Pediatr Blood Cancer. 2016 Jul;63(7):1163-7. doi: 10.1002/pbc.25970. Epub 2016 Mar 14.

Abstract

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.

Keywords: carcinoma; fibrolamellar; hepatocellular; protein kinase A.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence*
  • Carcinoma, Hepatocellular / classification
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Child
  • Child, Preschool
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / genetics*
  • Female
  • HSP40 Heat-Shock Proteins / genetics*
  • Humans
  • Liver Neoplasms / classification
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Oncogene Proteins, Fusion / genetics*
  • Sequence Deletion*

Substances

  • DNAJB1 protein, human
  • HSP40 Heat-Shock Proteins
  • Oncogene Proteins, Fusion
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
  • PRKACA protein, human

Supplementary concepts

  • Fibrolamellar hepatocellular carcinoma