Comparative functional genomics approach to identify bes

转基因小鼠已被广泛用于分析在肿瘤发展的多阶段进展过程中发生的细胞和遗传事件。然而，在许多情况下，如果不是所有情况下，还不确定老鼠模型在多大程度上忠实地再现了在相应的人类条件下观察到的特征1-3。这在很大程度上是由于缺乏在分子水平上直接比较小鼠人类肿瘤的方法。为了直接比较小鼠和人肝细胞癌的分子特征，比较了7种不同小鼠模型的68例肝癌和91例预定义亚类的人肝癌的基因表达谱，其中Myc、E2F1和Myc/E2F1小鼠的肝癌基因表达谱与人肝癌存活较好组的相似性最高，而Myc/Tgfa和DENA诱导的小鼠肝癌的表达谱与人肝癌存活较差组的相似性最高。正如预期的那样，Acox1基因敲除和环丙贝特诱导的肝癌的基因表达模式彼此具有最高的相似性，但未能模拟在人类肝癌中观察到的基因表达模式。我们的结论是，我们的方法，即比较功能癌基因组学，具有确定最合适的小鼠模型来研究人类癌症的巨大潜力。

Genetically modified mice have been extensively used for analyzing the cellular and genetic events that occur during the multistage progression of neoplastic development. However, in many cases, if not all, it is uncertain to what extend the mouse models faithfully reproduce features observed in the corresponding human conditions1-3. This is largely due to lack of methods for direct comparisons of mouse human tumors at the molecular level. To obtain direct comparison of the molecular features of mouse and human hepatocellular carcinoma (HCC), gene expression patterns of 68 HCC from 7 different mouse models were characterized and compared with 91 human HCC from pre-defined subclasses.Gene expression patterns of HCC from Myc, E2f1, and Myc/E2f1 mice had highest similarity with the better survival group of human HCC, while the expression patterns of Myc/Tgfa and DENA-induced mouse HCC had the highest similarity with the poorer survival group of human HCC. As expected, gene expression patterns of Acox1 knockout and ciprofibrate-induced HCC had highest similarity to each other, but failed to emulate those observed in human HCC. We conclude that our approach, the comparative functional oncogenomics, has the great potential to identify the most appropriate mouse models to study human cancers.