Author:
Simon Elana P.,Freije Catherine A.,Farber Benjamin A.,Lalazar Gadi,Darcy David G.,Honeyman Joshua N.,Chiaroni-Clarke Rachel,Dill Brian D.,Molina Henrik,Bhanot Umesh K.,La Quaglia Michael P.,Rosenberg Brad R.,Simon Sanford M.
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.
Funder
HHS | NIH | National Center for Advancing Translational Sciences
Leona M. and Harry B. Helmsley Charitable Trust
HHS | NIH | National Cancer Institute
The Ira Sohn Research Conference Foundation
Publisher
Proceedings of the National Academy of Sciences
Cited by
103 articles.
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