Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma Academic Article uri icon

Overview

MeSH Major

  • Carcinoma, Hepatocellular
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
  • HSP40 Heat-Shock Proteins
  • Liver Neoplasms
  • Oncogene Proteins, Fusion

abstract

  • Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare liver tumor affecting adolescents and young adults with no history of primary liver disease or cirrhosis. We identified a chimeric transcript that is expressed in FL-HCC but not in adjacent normal liver and that arises as the result of a ~400-kilobase deletion on chromosome 19. The chimeric RNA is predicted to code for a protein containing the amino-terminal domain of DNAJB1, a homolog of the molecular chaperone DNAJ, fused in frame with PRKACA, the catalytic domain of protein kinase A. Immunoprecipitation and Western blot analyses confirmed that the chimeric protein is expressed in tumor tissue, and a cell culture assay indicated that it retains kinase activity. Evidence supporting the presence of the DNAJB1-PRKACA chimeric transcript in 100% of the FL-HCCs examined (15/15) suggests that this genetic alteration contributes to tumor pathogenesis.

publication date

  • January 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4286414

Digital Object Identifier (DOI)

  • 10.1126/science.1249484

PubMed ID

  • 24578576

Additional Document Info

start page

  • 1010

end page

  • 4

volume

  • 343

number

  • 6174