Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy

To evaluate this possibility, gene expression microarray analysis was performed in mouse samples. The mouse tumors display increased expression of cell cycle and chromosomal instability associated genes. Remarkably, they are also enriched in human embryonic stem cell gene signatures, a characteristic feature of human aggressive tumors. Using cross-species comparison and meta-analytical approaches, we also observed that spontaneous mouse tumors display robust similarities with gene expression profiles of human tumors bearing mutated TP53, or displaying poor prognostic outcome, from multiple body tissues. We have obtained a 20-gene signature whose genes are overexpressed in mouse tumors and can identify human tumors with poor outcome from breast cancer, astrocytoma and multiple myeloma. This signature was consistently overexpressed in additional mouse tumors using microarray analysis. Two of the genes of this signature, AURKA and UBE2C, were validated in human breast and cervical cancer as potential biomarkers of malignancy.Our analyses demonstrate that these mouse models are promising preclinical tools aimed to search for malignancy biomarkers and to test targeted therapies of prospective use in human aggressive tumors and/or with p53 mutation or inactivation.Mouse models of human cancer have become essential tools for preclinical analysis of antitumoral drug discovery. To demonstrate that these models faithfully recapitulate human disease, a deep characterization of the tumors is required. Functional comparative genomics is one of the most powerful techniques for such validation. Moreover, such analyses have also evidenced that mouse models display the complexity of human cancer genomes. Cross-species studies using genomic-based technologies have indicated the preservation of oncogene transcriptional signatures [1,2] or the synteny of tumor-associated copy number alterations [3-5]. Furthermore, comparison between mouse and human samples have demonstrated the conserv