Transcriptomic characterization of fibrolamellar hepatocellular carcinoma.
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.
Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY 10065;
Elana P
EP
Simon
Presidential Fellows Laboratory, The Rockefeller University, New York, NY 10065;
Catherine A
CA
Freije
Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY 10065; Division of Pediatric Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
Benjamin A
BA
Farber
Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY 10065;
Gadi
G
Lalazar
Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY 10065; Division of Pediatric Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
David G
DG
Darcy
Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY 10065; Division of Pediatric Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
Joshua N
JN
Honeyman
Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY 10065;
Rachel
R
Chiaroni-Clarke
Proteomics Resource Center, The Rockefeller University, New York, NY 10065;
Brian D
BD
Dill
Proteomics Resource Center, The Rockefeller University, New York, NY 10065;
Henrik
H
Molina
Pathology Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
Umesh K
UK
Bhanot
Division of Pediatric Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
Michael P
MP
La Quaglia
Presidential Fellows Laboratory, The Rockefeller University, New York, NY 10065; John C. Whitehead Presidential Fellows Program, The Rockefeller University, New York, NY 10065.
Brad R
BR
Rosenberg
Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY 10065; simon@rockefeller.edu.
Sanford M
SM
Simon
D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D059467:Transcriptome
fusion gene; genomics; liver cancer; pediatric cancer; protein kinase