GSE144101 High-throughput sequencing analysis of a “hit and run” cell and animal model of KSHV tumorigenesis.

Contributors : E A Mesri ; J Naipauer ; M C AbbaSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusKaposi's sarcoma (KS), is an AIDS-associated neoplasm caused by the KS herpesvirus (KSHV). A mouse model of KSHV-dependent tumorigenicity, allowed us to induce KSHV viral-episome loss following tumor development to test the plausibility of “hit and run” mechanism by KSHV. RNA-seq-transcriptome analysis and CpG-methylation were performed on KSHV positive cells, KSHV positive tumors and tumors that developed following viral-episome loss. During KSHV tumorigenesis, hypo-methylation was detected of oncogenic and differentiation pathwa ys. In contrast, during tumorigenesis following KSHV-episome loss, a tendency towards hyper-methylation was detected. We found the same set of innate-immunity related mutations undetected in KSHV-infected cells but present in all KSHV-positive tumors, indicating that pre-existing host mutations that provide an in vivo growth advantage are clonally-selected and contribute to KSHV-tumorigenesis. We found de novo mutations related to cell proliferation that, together with the PDGFRAD842V, were responsible for driving tumorigenesis in absence of the KSHV-episomes. Virally-induced irreversible gene tic and epigenetic oncogenic alteration supports the possibility of “hit and run” KSHV-sarcomagenesis consistent with the existence of LANA-negative spindle-cells in KS lesions.

Source: GEO: Gene Expression Omnibus - January 23, 2020 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research