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.
authors.affiliation: Laboratory of Cellular Biophysics, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Honeyman
authors.forename: Elana P
authors.initials: EP
authors.lastname: Simon
authors.forename: Nicolas
authors.initials: N
authors.lastname: Robine
authors.forename: Rachel
authors.initials: R
authors.lastname: Chiaroni-Clarke
authors.forename: David G
authors.initials: DG
authors.lastname: Darcy
authors.forename: Irene Isabel P
authors.initials: II
authors.lastname: Lim
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Gleason
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Murphy
authors.forename: Brad R
authors.initials: BR
authors.lastname: Rosenberg
authors.forename: Lydia
authors.initials: L
authors.lastname: Teegan
authors.forename: Constantin N
authors.initials: CN
authors.lastname: Takacs
authors.forename: Sergio
authors.initials: S
authors.lastname: Botero
authors.forename: Rachel
authors.initials: R
authors.lastname: Belote
authors.forename: Soren
authors.initials: S
authors.lastname: Germer
authors.forename: Anne-Katrin
authors.initials: AK
authors.lastname: Emde
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vacic
authors.forename: Umesh
authors.initials: U
authors.lastname: Bhanot
authors.forename: Michael P
authors.initials: MP
authors.lastname: LaQuaglia
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Simon
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics*; D002872:Chromosome Deletion; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000737:chemistry / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D050956:HSP40 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: C494647:DNAJB1 protein, human; D050956:HSP40 Heat-Shock Proteins; D015514:Oncogene Proteins, Fusion; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; C517757:PRKACA protein, human