Zender, L., Spector, M. S., Xue, W., Flemming, P., Cordon-Cardo, C., Silke, J., Fan, S. T., Luk, J. M., Wigler, M. H., Hannon, G. J., Mu, D., Lucito, R., Powers, S., Lowe, S. W.
(June 2006)
Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach.
Cell, 125 (7).
pp. 1253-67.
ISSN 0092-8674 (Print)
Abstract
The heterogeneity and instability of human tumors hamper straightforward identification of cancer-causing mutations through genomic approaches alone. Herein we describe a mouse model of liver cancer initiated from progenitor cells harboring defined cancer-predisposing lesions. Genome-wide analyses of tumors in this mouse model and in human hepatocellular carcinomas revealed a recurrent amplification at mouse chromosome 9qA1, the syntenic region of human chromosome 11q22. Gene-expression analyses delineated cIAP1, a known inhibitor of apoptosis, and Yap, a transcription factor, as candidate oncogenes in the amplicon. In the genetic context of their amplification, both cIAP1 and Yap accelerated tumorigenesis and were required to sustain rapid growth of amplicon-containing tumors. Furthermore, cIAP1 and Yap cooperated to promote tumorigenesis. Our results establish a tractable model of liver cancer, identify two oncogenes that cooperate by virtue of their coamplification in the same genomic locus, and suggest an efficient strategy for the annotation of human cancer genes.
| Item Type: |
Paper
|
| Uncontrolled Keywords: |
Adaptor Proteins
Signal Transducing
genetics
Animals
Carcinoma
Hepatocellular genetics
Genes
p53
Genomics
Humans
Inhibitor of Apoptosis Proteins
genetics
Liver Neoplasms
genetics
Liver Neoplasms
Experimental/etiology/genetics/pathology
Mice
Mice
Knockout
Mutation
Nuclear Proteins
genetics
Oligonucleotide Array Sequence Analysis
Oncogenes
Phosphoproteins
genetics
Species Specificity
Trans-Activators
genetics |
| Subjects: |
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > endothelial progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > endothelial progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > endothelial progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell > endothelial progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell > endothelial progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell > endothelial progenitor cell
diseases & disorders > cancer > cancer types > liver cancer
organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell |
| CSHL Authors: |
|
| Communities: |
CSHL labs > Hannon lab
CSHL labs > Lowe lab
CSHL labs > Lucito lab
CSHL labs > Powers lab
CSHL labs > Wigler lab |
| Depositing User: |
CSHL Librarian
|
| Date: |
30 June 2006 |
| Date Deposited: |
05 Dec 2011 23:03 |
| Last Modified: |
18 Nov 2016 17:13 |
| PMCID: |
PMC3026384 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/22944 |
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