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.
Highlights
Since the approval of trastuzumab as a treatment for HER2positive breast cancer in 1998 by the FDA [1], tumorassociated antigens such as CD molecules, VEGF, and EGFR have been actively targeted for drug development by the pharmaceutical industry [2,3,4]
Several studies have shown that targeting neoantigens in T-cell-based immunotherapy is a promising approach for treatment of lung adenocarcinomas [6], leukemia [7], and melanoma [8, 9]
Tumor-Specific Neo-Antigen Detector” (TSNAD) can identify cancer somatic mutations following the best practices of the genome analysis toolkit (GATK) from the genome/exome sequencing data of tumor-normal pairs and determine HLA genotyping by SOAP-HLA [19]
Summary
Since the approval of trastuzumab as a treatment for HER2positive breast cancer in 1998 by the FDA [1], tumorassociated antigens such as CD molecules, VEGF, and EGFR have been actively targeted for drug development by the pharmaceutical industry [2,3,4]. Cancer is initialized by somatic driver mutations and other genetic instabilities, which are the molecular basis of the carcinogenesis process. Previous studies have used genomic data from the TCGA, Foundation Medicine Adult Cancer Clinical Dataset (FMAD), and their own cohorts to characterize neoantigens and their association with genetic alteration or with survival [14–. These studies did not focus on neoantigen profiling for gastric cancer patients.
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