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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Bibliographic Details
Published in:PloS one 2021-06, Vol.16 (6), p.e0251630-e0251630
Main Authors: Spaanderman, Ide T, Peters, Fleur S, Jongejan, Aldo, Redeker, Egbert J. W, Punt, Cornelis J. A, Bins, Adriaan D
Format: Article
Language:English
Subjects:
Analysis
Antigens
Biology and Life Sciences
Cancer
Care and treatment
Colon
Colon cancer
Colorectal cancer
Deoxyribonucleic acid
DNA
DNA methylation
DNA sequencing
Endometrium
Gastric cancer
Gene frequency
Gene loci
Gene sequencing
Genetic aspects
Genomes
Immunology
Immunotherapy
Infections
Informatics
Medicine and Health Sciences
Microsatellite instability
mRNA
Mutation
Oncology
Patients
Peptides
Research and analysis methods
Tumors
Uterine cancer
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0251630