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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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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. |
format | Online Article Text |
id | pubmed-3413665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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