title: Mouse p53-deficient cancer models as platforms for obtaining genomic predictors of human cancer clinical outcomes.
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.
authors.affiliation: Molecular Oncology Unit, CIEMAT, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Dueñas
authors.forename: Mirentxu
authors.initials: M
authors.lastname: Santos
authors.forename: Juan F
authors.initials: JF
authors.lastname: Aranda
authors.forename: Concha
authors.initials: C
authors.lastname: Bielza
authors.forename: Ana B
authors.initials: AB
authors.lastname: Martínez-Cruz
authors.forename: Corina
authors.initials: C
authors.lastname: Lorz
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: Eva M
authors.initials: EM
authors.lastname: Ciruelos
authors.forename: José L
authors.initials: JL
authors.lastname: Rodríguez-Peralto
authors.forename: Miguel
authors.initials: M
authors.lastname: Martín
authors.forename: Pedro
authors.initials: P
authors.lastname: Larrañaga
authors.forename: Jubrail
authors.initials: J
authors.lastname: Dahabreh
authors.forename: George P
authors.initials: GP
authors.lastname: Stathopoulos
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Paramio
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Escudero
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics; D000818:Animals; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm / Q000235:genetics; D005818:Genetic Engineering; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012867:Skin / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53