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| Status |
Public on Apr 01, 2015 |
| Title |
Specific Genomic and Transcriptomic Aberrations in Tumors Induced by Partial Hepatectomy of a Chronically Inflamed Murine Liver [aCGH] |
| Organism |
Mus musculus |
| Experiment type |
Genome variation profiling by array
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| Summary |
Background & Aims. Resection of hepatocellular carcinoma (HCC) tumors by partial hepatectomy (PHx) is associated with promoting hepatocarcinogenesis. We have previously reported that PHx promotes hepatocarcinogenesis in the Mdr2-knockout (Mdr2-KO) mouse, a model for inflammation-mediated HCC. Now, we explored the molecular mechanisms underlying the tumor-promoting effect of PHx in these mice. Methods. Using microarrays-based techniques, we compared genomic and transcriptomic profiles of HCC tumors developing in the Mdr2-KO mice either spontaneously or following PHx. Results. PHx accelerated HCC development in these mice by four months. PHx-induced tumors had only amplifications affecting multiple chromosomes and locating mainly near the acrocentric centromeres of murine chromosomes. Four different chromosomal regions were amplified each in at least three tumors. All tumors of untreated mice had chromosomal aberrations, including both deletions and amplifications. Comparison of gene expression profiles revealed a significantly enriched expression of oncogenes, chromosomal instability markers and E2F1 targets in the post-PHx compared to spontaneous tumors. Both tumor groups shared the same frequent amplification at chromosome 18. Here, we demonstrated that one of the regulatory genes encoded by this amplified region, Crem, was over-expressed in the nuclei of murine and human HCC cells in vivo, and that it stimulated proliferation of human HCC cells in vitro. Conclusions: PHx of a chronically inflamed liver directed tumor development to a discrete pathway characterized by amplification of specific chromosomal regions and expression of specific tumor-promoting genes. Crem is a new candidate HCC oncogene frequently amplified in this model and frequently over-expressed in human HCC.
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| Overall design |
To explore the mechanisms of the accelerated HCC development by PHx, we compared liver tumors and their matched non-tumor liver tissues between 9-month-old hepatectomized and 13-14-month-old untreated Mdr2-KO mice.
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| Contributor(s) |
Ella E, Heim D, Stoyanov E, Harari-Steinfeld R, Steinfeld I, Pappo O, Schnitzer Perlman T, Nachmansson N, Rivkin L, Olam D, Abramovitch R, Wege H, Galun E, Goldenberg D |
| Citation(s) |
25401338 |
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| Submission date |
Sep 15, 2014 |
| Last update date |
Jul 05, 2015 |
| Contact name |
Daniel Goldenberg |
| E-mail(s) |
[email protected]
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| Organization name |
Hadassah medical center
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| Department |
Gene therapy
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| Lab |
Goldenberg
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| Street address |
Ein Kerem
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| City |
Jerusalem |
| ZIP/Postal code |
12000 |
| Country |
Israel |
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| Platforms (1) |
| GPL11288 |
Agilent-015028 Mouse Genome CGH Microarray 4x44K (Feature Number version) |
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| Samples (12)
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| GSM1504348 |
Post-PHx-Mdr2/KO Liver vs Tumor (PHx1M) |
| GSM1504349 |
Post-PHx-Mdr2/KO Liver vs Tumor (PHx2F) |
| GSM1504350 |
Post-PHx-Mdr2/KO Liver vs Tumor (PHx3M) |
| GSM1504351 |
Post-PHx-Mdr2/KO Liver vs Tumor (PHx4M) |
| GSM1504352 |
Post-PHx-Mdr2/KO Liver vs Tumor (PHx5M) |
| GSM1504353 |
Post-PHx-Mdr2/KO Liver vs Tumor (PHx6F) |
| GSM1504354 |
Untreated-Mdr2/KO Liver vs Tumor (Spon5F) |
| GSM1504355 |
Untreated-Mdr2/KO Liver vs Tumor (Spon6F) |
| GSM1504356 |
Untreated-Mdr2/KO Liver vs Tumor (Spon1M) |
| GSM1504357 |
Untreated-Mdr2/KO Liver vs Tumor (Spon2M) |
| GSM1504358 |
Untreated-Mdr2/KO Liver vs Tumor (Spon3F) |
| GSM1504359 |
Untreated-Mdr2/KO Liver vs Tumor (Spon4F) |
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| This SubSeries is part of SuperSeries: |
| GSE61427 |
Specific Genomic and Transcriptomic Aberrations in Tumors Induced by Partial Hepatectomy of a Chronically Inflamed Murine Liver |
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| Relations |
| BioProject |
PRJNA261056 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE61423_RAW.tar |
139.9 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE61423_results.xls.gz |
767.2 Kb |
(ftp)(http) |
XLS |
| Processed data included within Sample table |
| Processed data are available on Series record |
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