Expression profiling and identification of novel genes in hepatocellular carcinomas

Liver cancer is the fifth most common cancer worldwide and unlike certain o ther cancers, such as colon cancer, a mutational model has not Set been dev eloped. We have performed gene expression profiling of normal and neoplasti c livers in C3H/HeJ mice treated with diethylnitrosamine. Using oligonucleo tide microarrays, we compared gene expression in liver tumors to three diff erent states of the normal liver: quiescent adult, regenerating adult, and newborn. Although each comparison revealed hundreds of differentially expre ssed genes, only 22 genes were found to be deregulated in the tumors in all three comparisons. Three of these genes were examined in human hepatocellu lar carcinomas and were found to be upregulated. As a second method of anal ysis, we used Representational Difference Analysis (RDA) to clone mRNA frag ments differentially expressed in Ih er tumors versus regenerating livers. We cloned several novel mRNAs that are differentially regulated in murine l iver tumors. Here we report the sequence of a novel cDNA whose expression i s upregulated in both murine and human hepatocellular carcinomas. Our resul ts suggest that DEN-treated mice provide an excellent model for human hepat ocellular carcinomas.