Genomic Amplification of an Endogenous Retrovirus in Zebrafish T-Cell Malignancies
ZFERV gene expression by normal and abnormal D. rerio T cells. Total RNA was tested by qRT-PCR of the ZFERV pol (a) and env (b) genes. Normal T cell RNA pooled from WIK fish ( and 18; lanes 1, 2) were used as control, and the “WIK T cells 16–31” sample was arbitrarily set to an expression value = 1. Premalignant T lymphocytes from hlk () and MYC-ER () fish had higher expression than WT fish (white bars; lanes 3, 9), and this higher transcription reached statistical significance. Individual cancers from hlk (; lanes 4–7) and MYC-ER (; lanes 10–15) fish are depicted with gray bars. Cancer cells from these fish invariably showed higher pol and env transcripts than T cells from WT fish, and nearly always had elevated RNA expression relative to normal T cells from these same two lines. Mean expression of pol and env in malignant T cells (black bars; lanes 8, 16) exceeded both WT and premalignant T cell transcript levels. Two cancers highlighted by asterisks (hlk T-ALL 4, hlk T-ALL 7; lanes 4, 5) were also tested for genomic copy number by qPCR. The hlk T-ALL 4 cancer had ZFERV copy number similar to hlk premalignant T cells (see Figure 4), and its pol and env expression also resembled hlk T cells. Cells from the hlk T-ALL 7 sample had high-level genomic ZFERV gains (see Figure 6), and likewise demonstrated dramatically increased ZFERV transcription.
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