Comparative Oncogenomic Analysis of Hepatocellular Carcinoma in Human and Rodent Models for Revealing Putative Cancer Genes

3709 Recently, several studies using cross-species comparative genomic analysis has proved to be a powerful strategy to identify putative cancer genes. The alignment of chromosome aberration and the consistence of gene expression between mouse and human tumors could effective narrowed down the minimum overlapping region and help to identify putative cancer genes. Previously, we have constructed an open access database OncoDB.HCC (http://oncodb.hcc.ibms.sinica.edu.tw) which integrated various genomic data in HCC to provide lines of evidence for revealing important aberrant cancer target genes and loci. Via comparative mapping of HCC loci in between human aberrant chromosomal regions and quantitative trait loci (QTLs) of mouse and rat HCC models we revealed 12 syntenic HCC regions and the putative human cancer genes located in those regions. In this study, the microarray data of mouse and rat HCC models were downloaded from public database. The comparative oncognomic analysis was performed by comparing the expression profiles between orthologous genes and then combined with the syntenic HCC region data. First, the human and rodent orthologous genes with concordant expression patterns in both species were listed. From the analysis of mouse and human expression profiles, 133 genes with concordant up (64 genes) and down (69 genes) regulated expression patterns were identified. From the rat and human expression profile analysis, 17 genes with concordant up (7 genes) and down (10 genes) regulated expression patterns were identified. The concordantly expressed genes in between human and rodent HCCs were analyzed by gene ontology and pathway analysis. We further integrated those concordant expressed genes onto 12 syntenic HCC regions and mouse/rat QTL for identification of putative cancer genes. In total, 5 putative oncogenes were found to be concordantly up regulated in both human and rat microarrays and located in human HCC chromosome copy number increase regions as well as mouse QTL syntenic regions. On the other hand, 2 putative oncogenes from rat microarray studies using similar criteria. Interestingly, no putative tumor suppressor genes were identified in this comparative oncogenomic analysis. Our results also suggested those genes could be the potential cancer genes for the corresponding rodent HCC models and played an important role in tumorigenesis of human and rodent. Further experimental validation should be performed using those rodent models. In conclusion, the cross-species comparative oncogenomic analysis could effectively filter putative cancer genes from heterogeneous and complicated oncogenomic data. Furthermore, this strategy would be valuable in dissecting the HCC tumorigenesis pathway between human and rodent as well as identifying representative rodent HCC models which would have plenty application in the HCC diagnosis and therapy.