Framing the potential of public frameshift peptides as immunotherapy targets in colon cancer
| Autor: | Adriaan D. Bins, Aldo Jongejan, Fleur S. Peters, Cornelis J. A. Punt, Ide T. Spaanderman, Egbert J.W. Redeker |
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| Přispěvatelé: | Experimental Immunology, Epidemiology and Data Science, AII - Cancer immunology, APH - Methodology, Human Genetics, ACS - Pulmonary hypertension & thrombosis, Amsterdam Reproduction & Development (AR&D), Oncology, CCA - Cancer biology and immunology, APH - Personalized Medicine |
| Rok vydání: | 2021 |
| Předmět: |
Reading Frames
Molecular biology Colorectal cancer medicine.medical_treatment Nonsense-mediated decay Cancer Treatment medicine.disease_cause Genome Sequencing techniques Medicine and Health Sciences Frameshift Mutation Stomach cancer Mutation Multidisciplinary RNA sequencing Oncology Colonic Neoplasms Medicine Microsatellite Microsatellite Instability Immunotherapy Research Article congenital hereditary and neonatal diseases and abnormalities Science Immunology Cancer Immunotherapy DNA sequencing Frameshift mutation Uterine Cancer Germline mutation Uterine cancer Gastrointestinal Tumors Genetics medicine Humans RNA Messenger neoplasms Colorectal Cancer business.industry Biology and Life Sciences Cancers and Neoplasms nutritional and metabolic diseases medicine.disease digestive system diseases Nonsense Mediated mRNA Decay Research and analysis methods Gastric Cancer Open reading frame Molecular biology techniques Cancer research Clinical Immunology Clinical Medicine Peptides business Gynecological Tumors Microsatellite Repeats |
| Zdroj: | PLoS ONE PLoS ONE, 16(6 June 2021):e0251630. Public Library of Science PLoS ONE, Vol 16, Iss 6, p e0251630 (2021) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0251630 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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