Transcriptomic characterization of fibrolamellar hepatocellular carcinoma

Elana P. Simon, Catherine A. Freije, Benjamin A. Farber, Gadi Lalazar, David G. Darcy, Joshua N. Honeyman, Rachel Chiaroni-Clarke, Brian D. Dill, Henrik Molina, Umesh K. Bhanot, Michael P. La Quaglia, Brad R. Rosenberg, Sanford M. Simon

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)E5916-E5925
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number44
DOIs
StatePublished - Nov 3 2015
Externally publishedYes

Keywords

  • Fusion gene
  • Genomics
  • Liver cancer
  • Pediatric cancer
  • Protein kinase

ASJC Scopus subject areas

  • General

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