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Establishment of Gastric Cancer Patient-derived Xenograft Models and Primary Cell Lines
Published on: July 19, 2019
Neoantigens Derived from Recurrently Mutated Genes as Potential Immunotherapy Targets for Gastric Cancer
Jie Zhou1, Wenyi Zhao2, Jingcheng Wu1
1Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
Abstract:
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.
Insights
Neoantigens offer targeted T-cell immunotherapy for gastric cancer patients with mutated genes. Researchers identified specific neoantigens from recurrently mutated genes as potential therapeutic targets.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Neoantigens are ideal targets for T-cell immunotherapy, particularly for tumors with undruggable mutations.
- T-cell immunotherapy presents a potential universal treatment applicable across HLA genotypes sharing common oncogenic mutations.
Purpose of the Study:
- To identify neoantigens for potential gastric cancer immunotherapy.
- To analyze somatic mutations and predict neoantigens in gastric cancer patients.
Main Methods:
- Whole exome sequencing was performed on 32 gastric cancer patients.
- TSNAD software was utilized to detect somatic mutations and predict neoantigens.
- Analysis included assessment of mutation patterns and neoantigen load across different tumor stages.
Main Results:
- High interpatient heterogeneity in somatic mutations was observed.
- Common mutations included C>A and C>T substitutions, suggesting active nucleotide excision repair.
- Neoantigen load was significantly higher in stage T1a compared to T2 or T4b.
- Six recurrently mutated driver genes (PIK3CA, FAT4, BRCA2, GNAQ, LRP1B, PREX2) were identified.
Conclusions:
- Neoantigens derived from recurrently mutated genes are promising targets for gastric cancer immunotherapy.
- Further investigation into these neoantigens, considering HLA alleles, is warranted for therapeutic development.
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