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A Comprehensive Survey of Genomic Alterations in Gastric Cancer Reveals Recurrent Neoantigens as Potential
Chao Chen1,2,3, Qiming Zhou3,4, Riping Wu5
1BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China.
Abstract:
Immunotherapy directed against cancer-specific neoantigens derived from non-silent mutants is a promising individualized strategy for cancer treatment. Neoantigens shared across patients could be used as a public resource for developing T cell-based therapy. To identify potential public neoantigens for therapy in gastric cancer (GC), 74 GC patients were enrolled in this study. Combined with the TCGA cohort and other published studies, whole exome sequencing data from 942 GC patients were used to detect somatic mutations and predict neoantigens shared by GC patients. The mutations pattern between our study and the TCGA cohort is comparable, and C > T is the most common substitution. The number of neoantigens was significantly higher in older patients (age ≥60) compared to younger patients (age <60), both in this study and the TCGA cohort. Recurrent neoantigens were found in eight genes (TP53, PIK3CA, PGM5, ERBB3, C6, TRIM49C, OR4C16, and KRAS) in this study. The neoantigen-associated mutations PIK3CA (p.H1047R) and TP53 (p.R175H) are common across several cancer types, indicating their potential usage. Overall, our study illustrates a comprehensive genomic landscape of GC and provides the recurrent neoantigens to facilitate further immunotherapy.
Insights
This study identified shared neoantigens in gastric cancer (GC) from 942 patients. These recurrent neoantigens, particularly from TP53 and PIK3CA genes, could advance T cell-based immunotherapy for gastric cancer patients.
Area of Science:
- Oncology
- Genomics
- Immunotherapy
Background:
- Immunotherapy targeting cancer neoantigens is a promising personalized treatment.
- Shared neoantigens offer potential for developing off-the-shelf T cell therapies.
- Gastric cancer (GC) requires novel therapeutic strategies.
Purpose of the Study:
- To identify shared neoantigens for potential T cell-based therapy in gastric cancer.
- To analyze the genomic landscape of GC and mutation patterns.
- To discover recurrent neoantigens across a large cohort.
Main Methods:
- Whole exome sequencing of 74 GC patients.
- Integrated data from TCGA and other studies for a total of 942 GC patients.
- Somatic mutation detection and neoantigen prediction.
Main Results:
- Identified recurrent neoantigens in eight genes, including TP53 and PIK3CA.
- Observed significantly more neoantigens in older patients (≥60 years).
- PIK3CA (p.H1047R) and TP53 (p.R175H) mutations are common across cancers.
Conclusions:
- The study provides a comprehensive genomic profile of GC.
- Identified recurrent neoantigens can facilitate the development of gastric cancer immunotherapies.
- Shared neoantigens represent a valuable resource for future T cell-based treatments.
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