Framing the potential of public frameshift peptides as immunotherapy targets in colon cancer.

Approximately 15% of Colon Cancers are Microsatellite Instable (MSI). Frameshift Peptides (FPs) formed in MSI Colon Cancer are potential targets for immunotherapeutic strategies. Here we comprehensively characterize the mutational landscape of 71 MSI Colon Cancer patients from the cancer genome atla...

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Autores principales:	Ide T Spaanderman, Fleur S Peters, Aldo Jongejan, Egbert J W Redeker, Cornelis J A Punt, Adriaan D Bins
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e6c081e7b941478cbccd90efecb713e0
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spelling	oai:doaj.org-article:e6c081e7b941478cbccd90efecb713e02021-12-02T20:03:50ZFraming the potential of public frameshift peptides as immunotherapy targets in colon cancer.1932-620310.1371/journal.pone.0251630https://doaj.org/article/e6c081e7b941478cbccd90efecb713e02021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251630https://doaj.org/toc/1932-6203Approximately 15% of Colon Cancers are Microsatellite Instable (MSI). Frameshift Peptides (FPs) formed in MSI Colon Cancer are potential targets for immunotherapeutic strategies. Here we comprehensively characterize the mutational landscape of 71 MSI Colon Cancer patients from the cancer genome atlas (TCGA). We confirm that the mutations in MSI Colon Cancers are frequently frameshift deletions (23% in MSI; 1% in microsatellite stable), We find that these mutations cluster at specific locations in the genome which are mutated in up to 41% of the patients. We filter these for an adequate variant allele frequency, a sufficient mean mRNA level and the formation of a Super Neo Open Reading Frame (SNORF). Finally, we check the influence of Nonsense Mediated Decay (MMD) by comparing RNA and DNA sequencing results. Thereby we identify a set of 20 NMD-escaping Public FPs (PFPs) that cover over 90% of MSI Colon, 62.2% of MSI Endometrial and 58.8% of MSI Stomach cancer patients and 3 out of 4 Lynch patients in the TCGA-COAD. This underlines the potential for PFP directed immunotherapy, both in a therapeutic and a prophylactic setting in multiple types of MSI cancers.Ide T SpaandermanFleur S PetersAldo JongejanEgbert J W RedekerCornelis J A PuntAdriaan D BinsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0251630 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ide T Spaanderman Fleur S Peters Aldo Jongejan Egbert J W Redeker Cornelis J A Punt Adriaan D Bins Framing the potential of public frameshift peptides as immunotherapy targets in colon cancer.
description	Approximately 15% of Colon Cancers are Microsatellite Instable (MSI). Frameshift Peptides (FPs) formed in MSI Colon Cancer are potential targets for immunotherapeutic strategies. Here we comprehensively characterize the mutational landscape of 71 MSI Colon Cancer patients from the cancer genome atlas (TCGA). We confirm that the mutations in MSI Colon Cancers are frequently frameshift deletions (23% in MSI; 1% in microsatellite stable), We find that these mutations cluster at specific locations in the genome which are mutated in up to 41% of the patients. We filter these for an adequate variant allele frequency, a sufficient mean mRNA level and the formation of a Super Neo Open Reading Frame (SNORF). Finally, we check the influence of Nonsense Mediated Decay (MMD) by comparing RNA and DNA sequencing results. Thereby we identify a set of 20 NMD-escaping Public FPs (PFPs) that cover over 90% of MSI Colon, 62.2% of MSI Endometrial and 58.8% of MSI Stomach cancer patients and 3 out of 4 Lynch patients in the TCGA-COAD. This underlines the potential for PFP directed immunotherapy, both in a therapeutic and a prophylactic setting in multiple types of MSI cancers.
format	article
author	Ide T Spaanderman Fleur S Peters Aldo Jongejan Egbert J W Redeker Cornelis J A Punt Adriaan D Bins
author_facet	Ide T Spaanderman Fleur S Peters Aldo Jongejan Egbert J W Redeker Cornelis J A Punt Adriaan D Bins
author_sort	Ide T Spaanderman
title	Framing the potential of public frameshift peptides as immunotherapy targets in colon cancer.
title_short	Framing the potential of public frameshift peptides as immunotherapy targets in colon cancer.
title_full	Framing the potential of public frameshift peptides as immunotherapy targets in colon cancer.
title_fullStr	Framing the potential of public frameshift peptides as immunotherapy targets in colon cancer.
title_full_unstemmed	Framing the potential of public frameshift peptides as immunotherapy targets in colon cancer.
title_sort	framing the potential of public frameshift peptides as immunotherapy targets in colon cancer.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/e6c081e7b941478cbccd90efecb713e0
work_keys_str_mv	AT idetspaanderman framingthepotentialofpublicframeshiftpeptidesasimmunotherapytargetsincoloncancer AT fleurspeters framingthepotentialofpublicframeshiftpeptidesasimmunotherapytargetsincoloncancer AT aldojongejan framingthepotentialofpublicframeshiftpeptidesasimmunotherapytargetsincoloncancer AT egbertjwredeker framingthepotentialofpublicframeshiftpeptidesasimmunotherapytargetsincoloncancer AT cornelisjapunt framingthepotentialofpublicframeshiftpeptidesasimmunotherapytargetsincoloncancer AT adriaandbins framingthepotentialofpublicframeshiftpeptidesasimmunotherapytargetsincoloncancer
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Framing the potential of public frameshift peptides as immunotherapy targets in colon cancer.

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