Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach

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)

URL: https://www.ncbi.nlm.nih.gov/pubmed/16814713
DOI: 10.1016/j.cell.2006.05.030

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: http://repository.cshl.edu/id/eprint/22944

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