Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma Journal Article


Authors: Honeyman, J. N.; Simon, E. P.; Robine, N.; Chiaroni-Clarke, R.; Darcy, D. G.; Lim, I. I. P.; Gleason, C. E.; Murphy, J. M.; Rosenberg, B. R.; Teegan, L.; Takacs, C. N.; Botero, S.; Belote, R.; Germer, S.; Emde, A. K.; Vacic, V.; Bhanot, U.; LaQuaglia, M. P.; Simon, S. M.
Article Title: Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma
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.
Keywords: liver cell carcinoma; carcinoma, hepatocellular; liver neoplasms; chromosome 19; gene; complex formation; protein; transcription, genetic; tumor cells, cultured; rna; gene expression regulation, neoplastic; dna; protein multimerization; bioassay; oncogene proteins, fusion; chromosomes, human, pair 19; protein structure, tertiary; pathogenicity; chromosome deletion; cell organelle; disease prevalence; hsp40 heat-shock proteins; detection method; humans; human; priority journal; article; cheating behavior; dnajb1 gene; fibrolamellar hepatocellular carcinoma; prkaca gene; cyclic amp-dependent protein kinase catalytic subunits
Journal Title: Science
Volume: 343
Issue: 6174
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Date Published: 2014-02-28
Start Page: 1010
End Page: 1014
Language: English
DOI: 10.1126/science.1249484
PROVIDER: scopus
PUBMED: 24578576
PMCID: PMC4286414
DOI/URL:
Notes: Export Date: 2 April 2014 -- CODEN: SCIEA -- Source: Scopus
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MSK Authors
  1. Umeshkumar Kapaldev Bhanot
    42 Bhanot
  2. Jennifer Michelle Murphy
    11 Murphy
  3. David Gene Darcy
    6 Darcy