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Carcinogenesis Advance Access published online on January 27, 2005
Carcinogenesis, doi:10.1093/carcin/bgi030
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Oxford University Press
Received December 1, 2004
Revised January 13, 2005
Accepted January 17, 2005

COMMENTARY

Comparative functional genomics for identifying models of human cancer

Ju-Seog Lee 1, Joe W. Grisham 1, and Snorri S. Thorgeirsson 1*

1 Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4262, USA

* To whom correspondence should be addressed.
Snorri S. Thorgeirsson, E-mail: snorri_thorgeirsson{at}nih.gov


  Abstract

Genetically modified mice with overexpressed and/or deleted genes have been extensively used to model human cancer. However it is uncertain to what extent the mouse models reproduce the corresponding cancers in humans. We have compared global gene expression patterns in human and mouse hepatocellular carcinomas (HCC) in an attempt to identify the mouse models that most extensively reproduce molecular pathways in the human tumors. The comparative analysis of gene expression patterns in murine and human HCC indicates that certain genetic mouse models closely reproduce the gene expression patterns of HCC in humans, while others do not. Identification of mouse models that reproduce the molecular features of specific human cancers (or subclasses of specific human cancers) promises to accelerate both the understanding of molecular pathogenesis of cancer and the discovery of therapeutic targets. We propose that this method, comparative functional genomics, can effectively be applied to the analysis of mouse models for other human cancers.


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