Mar 30, 2020

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

BioRxiv : the Preprint Server for Biology
Robert KoflerAdriaan D Bins

Abstract

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-COAD). 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 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 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.

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Mentioned in this Paper

Genome
Transposition of Intestine (Disorder)
Nucleic Acid Sequencing
Drosophila simulans
Drosophila
Diplopterygium simulans
Retrotransposons
Cellular Transposition
Cell Growth
Sequencing

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