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Mouse p53-Deficient Cancer Models as Platforms for Obtaining Genomic Predictors of Human Cancer Clinical Outcomes

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-d...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413665/
https://www.ncbi.nlm.nih.gov/pubmed/22880004
http://dx.doi.org/10.1371/journal.pone.0042494
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author 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
author_facet 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
author_sort Dueñas, Marta
collection PubMed
description 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.
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spelling pubmed-34136652012-08-09 Mouse p53-Deficient Cancer Models as Platforms for Obtaining Genomic Predictors of Human Cancer Clinical Outcomes 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 PLoS One Research Article 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. Public Library of Science 2012-08-07 /pmc/articles/PMC3413665/ /pubmed/22880004 http://dx.doi.org/10.1371/journal.pone.0042494 Text en © 2012 Dueñas et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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
Mouse p53-Deficient Cancer Models as Platforms for Obtaining Genomic Predictors of Human Cancer Clinical Outcomes
title Mouse p53-Deficient Cancer Models as Platforms for Obtaining Genomic Predictors of Human Cancer Clinical Outcomes
title_full Mouse p53-Deficient Cancer Models as Platforms for Obtaining Genomic Predictors of Human Cancer Clinical Outcomes
title_fullStr Mouse p53-Deficient Cancer Models as Platforms for Obtaining Genomic Predictors of Human Cancer Clinical Outcomes
title_full_unstemmed Mouse p53-Deficient Cancer Models as Platforms for Obtaining Genomic Predictors of Human Cancer Clinical Outcomes
title_short Mouse p53-Deficient Cancer Models as Platforms for Obtaining Genomic Predictors of Human Cancer Clinical Outcomes
title_sort mouse p53-deficient cancer models as platforms for obtaining genomic predictors of human cancer clinical outcomes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413665/
https://www.ncbi.nlm.nih.gov/pubmed/22880004
http://dx.doi.org/10.1371/journal.pone.0042494
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