Mouse p53-deficient cancer models as platforms for obtaining genomic predictors of human cancer clinical outcomes

• Published in: PloS one Vol. 7; no. 8; p. e42494
• Main Authors: Dueñas, Marta, Santos, Mirentxu, Aranda, Juan F, Bielza, Concha, Martínez-Cruz, Ana B, Lorz, Corina, Taron, Miquel, Ciruelos, Eva M, Rodríguez-Peralto, José L, Martín, Miguel, Larrañaga, Pedro, Dahabreh, Jubrail, Stathopoulos, George P, Rosell, Rafael, Paramio, Jesús M, García-Escudero, Ramón
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.08.2012; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Adenocarcinoma - classification; Adenocarcinoma - genetics; Animal models; Animals; Biology; Biomarkers; Breast cancer; Breast Neoplasms - classification; Breast Neoplasms - genetics; Brosimum alicastrum alicastrum; Cancer; Cancer genetics; Cancer therapies; Clinical outcomes; Disease Models, Animal; Female; Gene expression; Gene Expression Profiling; Genes; Genes, Neoplasm - genetics; Genetic aspects; Genetic Engineering; Genome, Human - genetics; Genomes; Genomics; Humans; Lung cancer; Lung diseases; Lung Neoplasms - classification; Lung Neoplasms - genetics; Mathematical models; Mathematics; Medical prognosis; Medicine; Metastasis; Mice; Mice, Transgenic; Multivariate Analysis; Mutation; Mutation - genetics; Oncology; Organs; p53 Protein; Patient outcomes; Proportional Hazards Models; Reproducibility of Results; Skin; Skin - metabolism; Skin - pathology; Skin cancer; Skin carcinoma; Stem cells; Survival Analysis; Transgenes; Transgenic mice; Treatment Outcome; Tumor proteins; Tumor Suppressor Protein p53 - antagonists & inhibitors; Tumor Suppressor Protein p53 - deficiency; Tumor Suppressor Protein p53 - metabolism; Tumors; Greece; Spain
• DOI: 10.1371/journal.pone.0042494
• ISSN: 1932-6203

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.