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Genomic Amplification of an Endogenous Retrovirus in Zebrafish T-Cell Malignancies
Advances in Hematology
  • J. Kimble Frazer, University of Utah
  • Lance A. Batchelor, University of Utah
  • Diana F. Bradley, University of Utah
  • Kim H. Brown, Portland State University
  • Kimberly P. Dobrinski, Brigham and Women’s Hospital
  • Charles Lee, Brigham and Women’s Hospital
  • Nikolaus S. Trede, University of Utah
Document Type
Publication Date
  • Zebra danio -- Genetics,
  • Zabra danio -- Mitochondrial DNA -- Analysis,
  • Zebra danio -- Development

Genomic instability plays a crucial role in oncogenesis. Somatically acquiredmutations can disable some genes and inappropriately activate others. In addition, chromosomal rearrangements can amplify, delete, or even fuse genes, altering their functions and contributing to malignant phenotypes. Using array comparative genomic hybridization (aCGH), a technique to detect numeric variations between different DNA samples, we examined genomes from zebrafish (Danio rerio) T-cell leukemias of three cancerprone lines. In all malignancies tested, we identified recurring amplifications of a zebrafish endogenous retrovirus. This retrovirus, ZFERV, was first identified due to high expression of proviral transcripts in thymic tissue from larval and adult fish.We confirmed ZFERV amplifications by quantitative PCR analyses of DNA from wild-type fish tissue and normal and malignant D. rerio T cells. We also quantified ZFERV RNA expression and found that normal and neoplastic T cells both produce retrovirally encoded transcripts, but most cancers show dramatically increased transcription. In aggregate, these data imply that ZFERV amplification and transcription may be related to T-cell leukemogenesis. Based on these data and ZFERV’s phylogenetic relation to viruses of the murine-leukemia-related virus class of gammaretroviridae, we posit that ZFERV may be oncogenic via an insertional mutagenesis mechanism.


* At the time of publication Kim H. Brown was affiliated with Brigham and Women’s Hospital.

Copyright © 2012 J. Kimble Frazer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Citation Information
Frazer JK, Batchelor LA, Bradley DF, Brown KH, Dobrinski KP, Lee C, Trede NS. Genomic Amplification of an Endogenous Retrovirus in Zebrafish T Cell Malignancies. Adv Hematol 2012; 2012, 627920