Autor: |
Ruangapirom L; Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand., Sutivijit N; Doctor of Medicine Program, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand., Teerapakpinyo C; Department of Medicine, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand., Mutirangura A; Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand., Doungkamchan C; Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. |
Abstrakt: |
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. |