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

doi:10.1073/pnas.1424894112

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 journal › Article › peer-review

85 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 language	English (US)
Pages (from-to)	E5916-E5925
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	112
Issue number	44
DOIs	https://doi.org/10.1073/pnas.1424894112
State	Published - Nov 3 2015
Externally published	Yes

Keywords

Fusion gene
Genomics
Liver cancer
Pediatric cancer
Protein kinase

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.1424894112

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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. (2015). Transcriptomic characterization of fibrolamellar hepatocellular carcinoma. Proceedings of the National Academy of Sciences of the United States of America, 112(44), E5916-E5925. https://doi.org/10.1073/pnas.1424894112

Simon, EP, Freije, CA, Farber, BA, Lalazar, G, Darcy, DG, Honeyman, JN, Chiaroni-Clarke, R, Dill, BD, Molina, H, Bhanot, UK, La Quaglia, MP, Rosenberg, BR & Simon, SM 2015, 'Transcriptomic characterization of fibrolamellar hepatocellular carcinoma', Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 44, pp. E5916-E5925. https://doi.org/10.1073/pnas.1424894112

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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 = "Fusion gene, Genomics, Liver cancer, Pediatric cancer, Protein kinase",

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

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AU - Simon, Elana P.

AU - Freije, Catherine A.

AU - Farber, Benjamin A.

AU - Lalazar, Gadi

AU - Darcy, David G.

AU - Honeyman, Joshua N.

AU - Chiaroni-Clarke, Rachel

AU - Dill, Brian D.

AU - Molina, Henrik

AU - Bhanot, Umesh K.

AU - La Quaglia, Michael P.

AU - Rosenberg, Brad R.

AU - Simon, Sanford M.

PY - 2015/11/3

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N2 - 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.

AB - 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.

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KW - Pediatric cancer

KW - Protein kinase

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Transcriptomic characterization of fibrolamellar hepatocellular carcinoma

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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