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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...

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Autores principales: Zhou, Jie, Zhao, Wenyi, Wu, Jingcheng, Lu, Jun, Ding, Yongfeng, Wu, Shanshan, Wang, Haiyong, Ding, Ding, Mo, Fan, Zhou, Zhan, Teng, Lisong, Chen, Shuqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
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.
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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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