Novel candidate cancer genes identified by a large-scale cross-species comparative oncogenomics approach

Comparative genomic hybridization (CGH) can reveal important disease genes but the large regions identified could sometimes contain hundreds of genes. Here we combine high-resolution CGH analysis of 598 human cancer cell lines with insertion sites isolated from 1,005 mouse tumors induced with the murine leukemia virus (MuLV). This cross-species oncogenomic analysis revealed candidate tumor suppressor genes and oncogenes mutated in both human and mouse tumors, making them strong candidates for novel cancer genes. A significant number of these genes contained binding sites for the stem cell transcription factors Oct4 and Nanog. Notably, mice carrying tumors with insertions in or near stem cell module genes, which are thought to participate in cell self-renewal, died significantly faster than mice without these insertions. A comparison of the profile we identified to that induced with the Sleeping Beauty (SB) transposon system revealed significant differences in the profile of recurrently mutated genes. Collectively, this work provides a rich catalogue of new candidate cancer genes for functional analysis.