A Comprehensive Survey of Genomic Mutations in Breast Cancer Reveals Recurrent Neoantigens as Potential Therapeutic Targets

Abstract

11Neoantigens are newly formed antigens generated by cancer cells but absent in 12 normal cells. With their high specificity and immunogenicity characteristic, 13 neoantigens are considered as an ideal target for immunotherapy. This study was 14 aimed to investigate the signature of neoantigens in breast cancer. Somatic mutations, 15including SNVs and indels, were obtained from cBioPortal of 5991 breast cancer 16 patients. For neoantigen prediction, 738 non-silent somatic variants present in at least 17 3 patients were selected., PIK3CA (38%), the highly mutated gene in breast cancer, 18can produce the highest number of neoantigens per gene. Some pan-cancer hotspot 19 mutations, such as PIK3CA E545K (6.93%), can be recognized by at least one HLA 20 molecule. Since there are more SNVs than indels in breast cancer, SNVs are the major 21 source of neoantigens. Patients with hormone receptor positive or HER2 positive are 22 more competent to produce neoantigens. Age, but not clinical stage, is a significant 23 contributory factor of neoantigens production. We believe a detailed description of 24 breast cancer neoantigens signatures could contribute to neoantigens based 25 immunotherapy development. 26