| Literature DB >> 24578576 |
Joshua N Honeyman1, Elana P Simon, Nicolas Robine, Rachel Chiaroni-Clarke, David G Darcy, Irene Isabel P Lim, Caroline E Gleason, Jennifer M Murphy, Brad R Rosenberg, Lydia Teegan, Constantin N Takacs, Sergio Botero, Rachel Belote, Soren Germer, Anne-Katrin Emde, Vladimir Vacic, Umesh Bhanot, Michael P LaQuaglia, Sanford M Simon.
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.Entities:
Mesh：
Substances：
Year: 2014 PMID： 24578576 PMCID： PMC4286414 DOI： 10.1126/science.1249484
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728