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Neoantigens Derived from Recurrently Mutated Genes as Potential Immunotherapy Targets for Gastric Cancer
Neoantigens are optimal tumor-specific targets for T-cell based immunotherapy, especially for patients with “undruggable” mutated driver genes. T-cell immunotherapy can be a “universal” treatment for HLA genotype patients sharing same oncogenic mutations. To identify potential neoantigens for therap...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595338/ https://www.ncbi.nlm.nih.gov/pubmed/31312661 http://dx.doi.org/10.1155/2019/8103142 |
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author | Zhou, Jie Zhao, Wenyi Wu, Jingcheng Lu, Jun Ding, Yongfeng Wu, Shanshan Wang, Haiyong Ding, Ding Mo, Fan Zhou, Zhan Teng, Lisong Chen, Shuqing |
author_facet | Zhou, Jie Zhao, Wenyi Wu, Jingcheng Lu, Jun Ding, Yongfeng Wu, Shanshan Wang, Haiyong Ding, Ding Mo, Fan Zhou, Zhan Teng, Lisong Chen, Shuqing |
author_sort | Zhou, Jie |
collection | PubMed |
description | Neoantigens are optimal tumor-specific targets for T-cell based immunotherapy, especially for patients with “undruggable” mutated driver genes. T-cell immunotherapy can be a “universal” treatment for HLA genotype patients sharing same oncogenic mutations. To identify potential neoantigens for therapy in gastric cancer, 32 gastric cancer patients were enrolled in our study. Whole exome sequencing data from these patients was processed by TSNAD software to detect cancer somatic mutations and predict neoantigens. The somatic mutations between different patients suggested a high interpatient heterogeneity. C>A and C>T substitutions are common, suggesting an active nucleotide excision repair. The number of predicted neoantigens was significantly higher in patients at stage T1a compared to in patients at T2 or T4b. Six genes (PIK3CA, FAT4, BRCA2, GNAQ, LRP1B, and PREX2) were found as recurrently mutated driver genes in our study. Combining with highly frequent HLA alleles, several neoantigens derived from six recurrently mutated genes were considered as potential targets for further immunotherapy. |
format | Online Article Text |
id | pubmed-6595338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-65953382019-07-16 Neoantigens Derived from Recurrently Mutated Genes as Potential Immunotherapy Targets for Gastric Cancer Zhou, Jie Zhao, Wenyi Wu, Jingcheng Lu, Jun Ding, Yongfeng Wu, Shanshan Wang, Haiyong Ding, Ding Mo, Fan Zhou, Zhan Teng, Lisong Chen, Shuqing Biomed Res Int Research Article Neoantigens are optimal tumor-specific targets for T-cell based immunotherapy, especially for patients with “undruggable” mutated driver genes. T-cell immunotherapy can be a “universal” treatment for HLA genotype patients sharing same oncogenic mutations. To identify potential neoantigens for therapy in gastric cancer, 32 gastric cancer patients were enrolled in our study. Whole exome sequencing data from these patients was processed by TSNAD software to detect cancer somatic mutations and predict neoantigens. The somatic mutations between different patients suggested a high interpatient heterogeneity. C>A and C>T substitutions are common, suggesting an active nucleotide excision repair. The number of predicted neoantigens was significantly higher in patients at stage T1a compared to in patients at T2 or T4b. Six genes (PIK3CA, FAT4, BRCA2, GNAQ, LRP1B, and PREX2) were found as recurrently mutated driver genes in our study. Combining with highly frequent HLA alleles, several neoantigens derived from six recurrently mutated genes were considered as potential targets for further immunotherapy. Hindawi 2019-06-13 /pmc/articles/PMC6595338/ /pubmed/31312661 http://dx.doi.org/10.1155/2019/8103142 Text en Copyright © 2019 Jie Zhou et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhou, Jie Zhao, Wenyi Wu, Jingcheng Lu, Jun Ding, Yongfeng Wu, Shanshan Wang, Haiyong Ding, Ding Mo, Fan Zhou, Zhan Teng, Lisong Chen, Shuqing Neoantigens Derived from Recurrently Mutated Genes as Potential Immunotherapy Targets for Gastric Cancer |
title | Neoantigens Derived from Recurrently Mutated Genes as Potential Immunotherapy Targets for Gastric Cancer |
title_full | Neoantigens Derived from Recurrently Mutated Genes as Potential Immunotherapy Targets for Gastric Cancer |
title_fullStr | Neoantigens Derived from Recurrently Mutated Genes as Potential Immunotherapy Targets for Gastric Cancer |
title_full_unstemmed | Neoantigens Derived from Recurrently Mutated Genes as Potential Immunotherapy Targets for Gastric Cancer |
title_short | Neoantigens Derived from Recurrently Mutated Genes as Potential Immunotherapy Targets for Gastric Cancer |
title_sort | neoantigens derived from recurrently mutated genes as potential immunotherapy targets for gastric cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595338/ https://www.ncbi.nlm.nih.gov/pubmed/31312661 http://dx.doi.org/10.1155/2019/8103142 |
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