In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 6 ( 2021-6-28), p. e0251630-
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). 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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0251630
DOI:
10.1371/journal.pone.0251630.g001
DOI:
10.1371/journal.pone.0251630.g002
DOI:
10.1371/journal.pone.0251630.g003
DOI:
10.1371/journal.pone.0251630.g004
DOI:
10.1371/journal.pone.0251630.g005
DOI:
10.1371/journal.pone.0251630.t001
DOI:
10.1371/journal.pone.0251630.s001
DOI:
10.1371/journal.pone.0251630.s002
DOI:
10.1371/journal.pone.0251630.s003
DOI:
10.1371/journal.pone.0251630.s004
DOI:
10.1371/journal.pone.0251630.s005
DOI:
10.1371/journal.pone.0251630.r001
DOI:
10.1371/journal.pone.0251630.r002
DOI:
10.1371/journal.pone.0251630.r003
DOI:
10.1371/journal.pone.0251630.r004
DOI:
10.1371/journal.pone.0251630.r005
DOI:
10.1371/journal.pone.0251630.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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