Genome and transcriptome profiling of fibrolamellar hepatocellular carcinoma demonstrates p53 and IGF2BP1 dysregulation Journal Article


Authors: Sorenson, E. C.; Khanin, R.; Bamboat, Z. M.; Cavnar, M. J.; Kim, T. S.; Sadot, E.; Zeng, S.; Greer, J. B.; Seifert, A. M.; Cohen, N. A.; Crawley, M. H.; Green, B. L.; Klimstra, D. S.; DeMatteo, R. P.
Article Title: Genome and transcriptome profiling of fibrolamellar hepatocellular carcinoma demonstrates p53 and IGF2BP1 dysregulation
Abstract: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of HCC that most frequently affects young adults. Because of its rarity and an absence of preclinical models, our understanding of FL-HCC is limited. Our objective was to analyze chromosomal alterations and dysregulated gene expression in tumor specimens collected at a single center during two decades of experience with FL-HCC. We analyzed 38 specimens from 26 patients by array comparative genomic hybridiziation (aCGH) and 35 specimens from 15 patients by transcriptome sequencing (RNA-seq). All tumor specimens exhibited genomic instability, with a higher frequency of genomic amplifications or deletions in metastatic tumors. The regions encoding 71 microRNAs (miRs) were deleted in at least 25% of tumor specimens. Five of these recurrently deleted miRs targeted the insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) gene product, and a correlating 100-fold upregulation of IGF2BP1 mRNA was seen in tumor specimens. Transcriptome analysis demonstrated intrapatient tumor similarity, independent of recurrence site or time. The p53 tumor suppressor pathway was downregulated as demonstrated by both aCGH and RNA-seq analysis. Notch, EGFR, NRAS, and RB1 pathways were also significantly dysregulated in tumors compared with normal liver tissue. The findings illuminate the genomic and transcriptomic landscape of this rare disease and provide insight into dysregulated oncogenic pathways and potential therapeutic targets in FL-HCC. © 2017 Sorenson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Journal Title: PLoS ONE
Volume: 12
Issue: 5
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2017-05-09
Start Page: e0176562
Language: English
DOI: 10.1371/journal.pone.0176562
PROVIDER: scopus
PMCID: PMC5423588
PUBMED: 28486549
DOI/URL:
Notes: Article -- Export Date: 2 June 2017 -- Source: Scopus
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MSK Authors
  1. Ronald P DeMatteo
    637 DeMatteo
  2. David S Klimstra
    978 Klimstra
  3. Michael Joseph Cavnar
    30 Cavnar
  4. Raya Khanin
    46 Khanin
  5. Shan Zeng
    26 Zeng
  6. Zubin Mickey Bamboat
    33 Bamboat
  7. Jonathan Bruce Greer
    13 Greer
  8. Teresa Sora Kim
    23 Kim
  9. Megan Hannon Crawley
    12 Crawley
  10. Benjamin Lawrence Green
    10 Green
  11. Noah Avram Cohen
    19 Cohen
  12. Adrian Marcel Seifert
    16 Seifert
  13. Eran Sadot
    38 Sadot