Identification of Shared Neoantigens in BRCA1-Related Breast Cancer
Lucksica Ruangapirom1, Nannapat Sutivijit2, Chinachote Teerapakpinyo3
1Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Abstract:
Personalized neoantigen-based cancer vaccines have been shown to be safe and immunogenic in cancer patients; however, the manufacturing process can be costly and bring about delays in treatment. Using off-the-shelf cancer vaccines targeting shared neoantigens may circumvent these problems. Unique mutational signatures and similar phenotypes found among BRCA1-mutated breast cancer make it an ideal candidate for discovering shared neoantigens within the group. We obtained genome sequencing data of breast cancer samples with or without somatic BRCA1 mutations (BRCA1-positive and BRCA1-negative, respectively) from the three public cancer databases; The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Catalogue of Somatic Mutations in Cancer (COSMIC); and from three studies with whole genome/exome sequencing data of samples with germline BRCA1 mutations. Data were analyzed separately within the same database/cohort. We found PIK3CA H1047R, E545K, E542K, and N345K recurrently in BRCA1-negative groups across all databases, whereas recurrent somatic mutations in BRCA1-positive groups were discordant among databases. For germline BRCA1-mutated breast cancer, TP53 R175H was unanimously the most frequent mutation among the three germline cohorts. Our study provides lists of potential shared neoantigens among BRCA1-related breast cancer, which may be used in developing off-the-shelf neoantigen-based vaccines.
Insights
Off-the-shelf cancer vaccines targeting shared neoantigens offer a promising alternative to personalized treatments for BRCA1-mutated breast cancer. This study identifies potential shared neoantigens for vaccine development.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Personalized neoantigen vaccines are safe and immunogenic but costly and time-consuming.
- Off-the-shelf vaccines targeting shared neoantigens could overcome these limitations.
- BRCA1-mutated breast cancer presents unique mutational signatures suitable for shared neoantigen discovery.
Purpose of the Study:
- To identify shared neoantigens in BRCA1-related breast cancer for developing off-the-shelf vaccines.
- To analyze genomic data from public databases and germline BRCA1 mutation studies.
- To compare mutation profiles between BRCA1-positive and BRCA1-negative breast cancer cohorts.
Main Methods:
- Retrieved and analyzed whole genome/exome sequencing data from TCGA, ICGC, COSMIC, and germline mutation studies.
- Compared somatic mutation frequencies within BRCA1-positive and BRCA1-negative breast cancer groups.
- Identified recurrent mutations across different databases and cohorts.
Main Results:
- PIK3CA mutations (H1047R, E545K, E542K, N345K) were recurrent in BRCA1-negative breast cancer across databases.
- Recurrent somatic mutations in BRCA1-positive groups varied between databases.
- TP53 R175H was the most frequent mutation in germline BRCA1-mutated breast cancer cohorts.
Conclusions:
- Identified potential shared neoantigens for BRCA1-related breast cancer.
- Findings support the development of off-the-shelf neoantigen-based vaccines.
- This approach may accelerate treatment for patients with BRCA1-mutated breast cancer.
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