J. Kimble Frazer was supported by Eunice Kennedy Shriver NICHD Award K08-HD053350 and the CHRC at the University of Utah. Nikolaus S. Trede was supported by NIAID Award R21- AI079784 and theHuntsman Cancer Foundation.Huntsman Cancer Institute core facilities supported by NCI P30- CA042014 also contributed to this work.
Advances in Hematology
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.
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