Transcriptomic characterization of fibrolamellar hepatocellular carcinoma Journal Article

   


Authors: Simon, E. P.; Freije, C. A.; Farber, B. A.; Lalazar, G.; Darcy, D. G.; Honeyman, J. N.; Chiaroni-Clarke, R.; Dill, B. D.; Molina, H.; Bhanot, U. K.; La Quaglia, M. P.; Rosenberg, B. R.; Simon, S. M.
Article Title: Transcriptomic characterization of fibrolamellar hepatocellular carcinoma
Abstract: Fibrolamellar hepatocellular carcinoma (FLHCC) tumors all carry a deletion of ∼400 kb in chromosome 19, resulting in a fusion of the genes for the heat shock protein, DNAJ (Hsp40) homolog, subfamily B, member 1, DNAJB1, and the catalytic subunit of protein kinase A, PRKACA. The resulting chimeric transcript produces a fusion protein that retains kinase activity. No other recurrent genomic alterations have been identified. Here we characterize the molecular pathogenesis of FLHCC with transcriptome sequencing (RNA sequencing). Differential expression (tumor vs. adjacent normal tissue) was detected for more than 3,500 genes (log2 fold change ≥1, false discovery rate ≤0.01), many of which were distinct from those found in hepatocellular carcinoma. Expression of several known oncogenes, such as ErbB2 and Aurora Kinase A, was increased in tumor samples. These and other dysregulated genes may serve as potential targets for therapeutic intervention.
Keywords: signal transduction; epidermal growth factor; clinical article; controlled study; human tissue; protein expression; protein phosphorylation; liver cell carcinoma; polymerase chain reaction; epidermal growth factor receptor 2; proteomics; transcriptomics; neuroendocrine tumor; extracellular matrix; quantitative analysis; fusion gene; genomics; gene control; liver cancer; upregulation; cancer tissue; cell cycle regulation; cell interaction; cell metabolism; protein kinase; rna sequence; aurora a kinase; cyclic amp dependent protein kinase; molecular pathology; pediatric cancer; estrogen synthesis; wnt signaling pathway; human; priority journal; article; fibrolamellar hepatocellular carcinoma
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 112
Issue: 44
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2015-11-03
Start Page: E5916
End Page: E5925
Language: English
DOI: 10.1073/pnas.1424894112
PROVIDER: scopus
PMCID: PMC4640752
PUBMED: 26489647
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84946601391&partnerID=40&md5=8667953c816f3ba835dc99fa5b08acef
Notes: Export Date: 2 December 2015 -- Source: Scopus
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MSK Authors
  1. Michael P La Quaglia
    411 La Quaglia
  2. Joshua N Honeyman
    21 Honeyman
  3. Umeshkumar Kapaldev Bhanot
    93 Bhanot
  4. David Gene Darcy
    7 Darcy
  5. Benjamin Asher Farber
    12 Farber
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