Genomic Amplification of an Endogenous Retrovirus in Zebrafish T-Cell Malignancies
Date
2012-04-17
Journal Title
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Publisher
Advances in Hematology, Hindawi Publishing Corporation
Abstract
Genomic instability plays a crucial role in oncogenesis. Somatically acquired mutations 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.
Description
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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Keywords
Carcinogenesis, Oncogenesis, Comparative genomic hybridization, Danio rerio
Citation
J.Kimble Frazer, Lance A. Batchelor, Diana F. Bradley, et al., “GenomicAmplification of an Endogenous Retrovirus in Zebrafish T-Cell Malignancies,” Advances in Hematology, vol. 2012, Article ID 627920, 12 pages, 2012. https://doi.org/10.1155/2012/627920.