NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE144101 Query DataSets for GSE144101
Status Public on Jan 23, 2020
Title High-throughput sequencing analysis of a “hit and run” cell and animal model of KSHV tumorigenesis. [RNA-Seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Kaposi'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 pathways. 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 genetic 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.
 
Overall design KSHV-infected KS lesions are composed of latently-infected cells, as well as cells expressing lytic genes that have been implicated in the development of the KS angioproliferative phenotype. The existence of KS lesions with varying levels of KSHV-infected cells suggests also the existence of virus-independent “hit and run” mechanisms of sarcomagenesis, whereby viral infection irreversibly induce genetic or epigenetic oncogenic alterations in host cells. We used the unique mECK36 animal model of multistep KSHV sarcomagenesis to dissect transcriptional, genetic and epigenetic mechanisms of KSHV direct and in-direct (“hit and run”) sarcomagenesis in an unbiased high-throughput fashion. These analyses revealed that KSHV in vivo tumorigenesis: A) Occurs predominantly with CpG hypo-methylation of oncogenic and differentiation pathways. B) Selects for pre-existing host mutations that allow the KSHV oncovirus to express the oncogenic lytic program by creating permissive environment for viral-induced innate immunity and inflammation, which provides a selective advantage in vivo conducive to tumorigenesis.
 
Contributor(s) Mesri EA, Naipauer J, Abba MC
Citation(s) 32603362, 34222014
Submission date Jan 22, 2020
Last update date Jul 08, 2021
Contact name Martin Carlos Abba
E-mail(s) mcabba@gmail.com
Phone 054-221-4236711
Organization name School of Medical Sciences - UNLP
Lab CINIBA
Street address 60 y 120
City La Plata
State/province Buenos Aires
ZIP/Postal code 1900
Country Argentina
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (15)
GSM4279921 KSHV (+) cells [DS001accepted_hitsmouse]
GSM4279922 KSHV (+) cells [DS003accepted_hitsmouse]
GSM4279923 KSHV (+) tumors [DS005accepted_hitsmouse]
This SubSeries is part of SuperSeries:
GSE148742 High-throughput sequencing analysis of a “hit and run” cell and animal model of KSHV tumorigenesis.
Relations
BioProject PRJNA602753
SRA SRP244101

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE144101_Preprocessed_datamatrix.csv.gz 1.1 Mb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap