Application of comparative functional genomics to identify best-fit mouse models to study human cancer

Ju Seog Lee, In Sun Chu, Arsen Mikaelyan, Diego F. Calvisi, Jeonghoon Heo, Janardan K. Reddy, Snorri S. Thorgeirsson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

356 Scopus citations

Abstract

Genetically modified mice have been extensively used for analyzing the molecular events that occur during tumor development. In many, if not all, cases, however, it is uncertain to what extent the mouse models reproduce features observed in the corresponding human conditions1-3. This is due largely to lack of precise methods for direct and comprehensive comparison at the molecular level of the mouse and human tumors. Here we use global gene expression patterns of 68 hepatocellular carcinomas (HCCs) from seven different mouse models and 91 human HCCs from predefined subclasses4 to obtain direct comparison of the molecular features of mouse and human HCCs. Gene expression patterns in HCCs from Myc, E2f1 and Myc E2f1 transgenic mice were most similar to those of the better survival group of human HCCs, whereas the expression patterns in HCCs from Myc Tgfa transgenic mice and in diethylnitrosamine-induced mouse HCCs were most similar to those of the poorer survival group of human HCCs. Gene expression patterns in HCCs from Acox1 -/- mice and in ciprofibrate-induced HCCs were least similar to those observed in human HCCs. We conclude that our approach can effectively identify appropriate mouse models to study human cancers.

Original languageEnglish (US)
Pages (from-to)1306-1311
Number of pages6
JournalNature Genetics
Volume36
Issue number12
DOIs
StatePublished - Dec 1 2004

ASJC Scopus subject areas

  • Genetics

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