Genomic Amplification of an Endogenous Retrovirus in Zebrafish T-Cell Malignancies
Autor: | Charles Lee, Nikolaus S. Trede, Diana F. Bradley, Kimberly P. Dobrinski, J. Kimble Frazer, Kim H. Brown, Lance Batchelor |
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Rok vydání: | 2012 |
Předmět: |
Genome instability
Genetics 0303 health sciences Article Subject biology Endogenous retrovirus Hematology medicine.disease_cause biology.organism_classification 3. Good health Insertional mutagenesis 03 medical and health sciences 0302 clinical medicine Retrovirus 030220 oncology & carcinogenesis medicine Diseases of the blood and blood-forming organs RC633-647.5 Carcinogenesis Gene Zebrafish Research Article 030304 developmental biology Comparative genomic hybridization |
Zdroj: | Advances in Hematology, Vol 2012 (2012) Advances in Hematology |
ISSN: | 1687-9112 1687-9104 |
DOI: | 10.1155/2012/627920 |
Popis: | 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 cancer-prone 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 malignantD. rerioT 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. |
Databáze: | OpenAIRE |
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