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| Status |
Public on Jul 03, 2012 |
| Title |
mRNA expression profiling of hepatocellular carcinoma induced by AAV in vivo gene targeting at the Rian locus |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The distinct phenotypic and prognostic subclasses of human hepatocellular carcinoma (HCC) are difficult to reproduce in animal experiments. Here we have used in vivo gene targeting to insert an enhancer-promoter element at an imprinted chromosome 12 locus in mice, thereby converting ~1 in 20,000 normal hepatocytes into a focus of HCC with a single genetic modification. A 300 kb chromosomal domain containing multiple mRNAs, snoRNAs and microRNAs was activated surrounding the integration site. An identical domain was activated at the syntenic locus in a specific molecular subclass of spontaneous human HCCs with a similar histological phenotype, which was associated with partial loss of DNA methylation. These findings demonstrate the accuracy of in vivo gene targeting in modeling human cancer, and suggest future applications in studying various tumors in diverse animal species. In addition, similar insertion events produced by randomly integrating vectors could be a concern for liver-directed human gene therapy.
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| |
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| Overall design |
Three individual liver tumor tissue and their adjacent normal liver tissue were used for mRNA array analysis
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| Contributor(s) |
Wang P, Xu M, Toffanin S, Li Y, Llovet JM, Russell DW |
| Citation(s) |
22733778 |
| |
| Submission date |
Jan 30, 2012 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Mei Xu |
| E-mail(s) |
mxu@u.washington.edu
|
| Organization name |
University of Washington
|
| Street address |
1959 NE Pacific ave N
|
| City |
Seattle |
| ZIP/Postal code |
98195 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE35404 |
miRNA and mRNA expression profiling of hepatocellular carcinoma induced by AAV in vivo gene targeting at the Rian locus |
|
| Relations |
| BioProject |
PRJNA156061 |
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