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

Lee, Ju-Seog and Chu, In-Sun and Mikaelyan, Arsen and Calvisi, Diego Francesco and Heo, Jeonghoon and Reddy, Janardan K. and Thorgeirsson, Snorri S. (2004) Application of comparative functional genomics to identify best-fit mouse models to study human cancer. Nature Genetics, Vol. 36 (12), p. 1306-1311. eISSN 1546-1718. Article.

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DOI: 10.1038/ng1481

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.

Item Type:Article
ID Code:1249
Status:Published
Refereed:Yes
Uncontrolled Keywords:Human cancer, hepatocellular carcinomas, Myc, mouse models, comparative functional genomics
Subjects:Area 06 - Scienze mediche > MED/04 Patologia generale
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:Nature Publishing Group
eISSN:1546-1718
Deposited On:18 Aug 2009 10:04

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