Abstract
Mutations in the TP53 gene are very common in human cancers, and are associated with poor clinical outcome. Transgenic mouse models lacking the Trp53 gene or that express mutant Trp53 transgenes produce tumours with malignant features in many organs. We previously showed the transcriptome of a p53-deficient mouse skin carcinoma model to be similar to those of human cancers with TP53 mutations and associated with poor clinical outcomes. This report shows that much of the 682-gene signature of this murine skin carcinoma transcriptome is also present in breast and lung cancer mouse models in which p53 is inhibited. Further, we report validated gene-expression-based tests for predicting the clinical outcome of human breast and lung adenocarcinoma. It was found that human patients with cancer could be stratified based on the similarity of their transcriptome with the mouse skin carcinoma 682-gene signature. The results also provide new targets for the treatment of p53-defective tumours.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / classification
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Adenocarcinoma / genetics
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Animals
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Breast Neoplasms / classification
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Breast Neoplasms / genetics*
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Disease Models, Animal
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Female
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Gene Expression Profiling
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Genes, Neoplasm / genetics
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Genetic Engineering
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Genome, Human / genetics*
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Genomics*
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Humans
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Lung Neoplasms / classification
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Lung Neoplasms / genetics*
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Mice
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Mice, Transgenic
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Multivariate Analysis
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Mutation / genetics
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Proportional Hazards Models
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Reproducibility of Results
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Skin / metabolism
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Skin / pathology
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Survival Analysis
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Treatment Outcome
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Tumor Suppressor Protein p53 / antagonists & inhibitors
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Tumor Suppressor Protein p53 / deficiency*
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Tumor Suppressor Protein p53 / metabolism*
Substances
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Tumor Suppressor Protein p53
Grants and funding
Oncocycle S2006/BIO-0232 (CAM), ISCIII-RETIC RD06/0020 (MICINN), and SAF2008-00121 (MICINN). J.M.P. was the recipient of a grant from the Fundación Sandra Ibarra. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.