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Mutanome and expression of immune response genes in microsatellite stable colon cancer

The aim of this study was to analyze the impact of the mutanome in the prognosis of microsatellite stable stage II CRC tumors. The exome of 42 stage II, microsatellite stable, colon tumors (21 of them relapse) and their paired mucosa were sequenced and analyzed. Although some pathways accumulated mo...

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Autores principales: Sanz-Pamplona, Rebeca, Gil-Hoyos, Raúl, López-Doriga, Adriana, Alonso, M. Henar, Aussó, Susanna, Molleví, David G., Santos, Cristina, Sanjuán, Xavier, Salazar, Ramón, Alemany, Ramón, Moreno, Víctor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951244/
https://www.ncbi.nlm.nih.gov/pubmed/26871478
http://dx.doi.org/10.18632/oncotarget.7293
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author Sanz-Pamplona, Rebeca
Gil-Hoyos, Raúl
López-Doriga, Adriana
Alonso, M. Henar
Aussó, Susanna
Molleví, David G.
Santos, Cristina
Sanjuán, Xavier
Salazar, Ramón
Alemany, Ramón
Moreno, Víctor
author_facet Sanz-Pamplona, Rebeca
Gil-Hoyos, Raúl
López-Doriga, Adriana
Alonso, M. Henar
Aussó, Susanna
Molleví, David G.
Santos, Cristina
Sanjuán, Xavier
Salazar, Ramón
Alemany, Ramón
Moreno, Víctor
author_sort Sanz-Pamplona, Rebeca
collection PubMed
description The aim of this study was to analyze the impact of the mutanome in the prognosis of microsatellite stable stage II CRC tumors. The exome of 42 stage II, microsatellite stable, colon tumors (21 of them relapse) and their paired mucosa were sequenced and analyzed. Although some pathways accumulated more mutations in patients exhibiting good or poor prognosis, no single somatic mutation was associated with prognosis. Exome sequencing data is also valuable to infer tumor neoantigens able to elicit a host immune response. Hence, putative neoantigens were identified by combining information about missense mutations in each tumor and HLAs genotypes of the patients. Under the hypothesis that neoantigens should be correctly presented in order to activate the immune response, expression levels of genes involved in the antigen presentation machinery were also assessed. In addition, CD8A level (as a marker of T-cell infiltration) was measured. We found that tumors with better prognosis showed a tendency to generate a higher number of immunogenic epitopes, and up-regulated genes involved in the antigen processing machinery. Moreover, tumors with higher T-cell infiltration also showed better prognosis. Stratifying by consensus molecular subtype, CMS4 tumors showed the highest association of expression levels of genes involved in the antigen presentation machinery with prognosis. Thus, we hypothesize that a subset of stage II microsatellite stable CRC tumors are able to generate an immune response in the host via MHC class I antigen presentation, directly related with a better prognosis.
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spelling pubmed-49512442016-07-21 Mutanome and expression of immune response genes in microsatellite stable colon cancer Sanz-Pamplona, Rebeca Gil-Hoyos, Raúl López-Doriga, Adriana Alonso, M. Henar Aussó, Susanna Molleví, David G. Santos, Cristina Sanjuán, Xavier Salazar, Ramón Alemany, Ramón Moreno, Víctor Oncotarget Research Paper The aim of this study was to analyze the impact of the mutanome in the prognosis of microsatellite stable stage II CRC tumors. The exome of 42 stage II, microsatellite stable, colon tumors (21 of them relapse) and their paired mucosa were sequenced and analyzed. Although some pathways accumulated more mutations in patients exhibiting good or poor prognosis, no single somatic mutation was associated with prognosis. Exome sequencing data is also valuable to infer tumor neoantigens able to elicit a host immune response. Hence, putative neoantigens were identified by combining information about missense mutations in each tumor and HLAs genotypes of the patients. Under the hypothesis that neoantigens should be correctly presented in order to activate the immune response, expression levels of genes involved in the antigen presentation machinery were also assessed. In addition, CD8A level (as a marker of T-cell infiltration) was measured. We found that tumors with better prognosis showed a tendency to generate a higher number of immunogenic epitopes, and up-regulated genes involved in the antigen processing machinery. Moreover, tumors with higher T-cell infiltration also showed better prognosis. Stratifying by consensus molecular subtype, CMS4 tumors showed the highest association of expression levels of genes involved in the antigen presentation machinery with prognosis. Thus, we hypothesize that a subset of stage II microsatellite stable CRC tumors are able to generate an immune response in the host via MHC class I antigen presentation, directly related with a better prognosis. Impact Journals LLC 2016-02-09 /pmc/articles/PMC4951244/ /pubmed/26871478 http://dx.doi.org/10.18632/oncotarget.7293 Text en Copyright: © 2016 Sanz-Pamplona et al. http://creativecommons.org/licenses/by/2.5/ 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 credited.
spellingShingle Research Paper
Sanz-Pamplona, Rebeca
Gil-Hoyos, Raúl
López-Doriga, Adriana
Alonso, M. Henar
Aussó, Susanna
Molleví, David G.
Santos, Cristina
Sanjuán, Xavier
Salazar, Ramón
Alemany, Ramón
Moreno, Víctor
Mutanome and expression of immune response genes in microsatellite stable colon cancer
title Mutanome and expression of immune response genes in microsatellite stable colon cancer
title_full Mutanome and expression of immune response genes in microsatellite stable colon cancer
title_fullStr Mutanome and expression of immune response genes in microsatellite stable colon cancer
title_full_unstemmed Mutanome and expression of immune response genes in microsatellite stable colon cancer
title_short Mutanome and expression of immune response genes in microsatellite stable colon cancer
title_sort mutanome and expression of immune response genes in microsatellite stable colon cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951244/
https://www.ncbi.nlm.nih.gov/pubmed/26871478
http://dx.doi.org/10.18632/oncotarget.7293
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