Abstract P5-13-05: Profiling of APOBEC3 dysregulation in breast cancer

Abstract

Abstract DNA of many breast tumors is barraged by C-to-T/G mutations within TCW (W:T,A). These mutations are attributed to the aberrant expression and activity of APOBEC3 enzymes. They have been shown to account for many driver mutations in genes such as PIK3CA, ERBB2, and PPP2R1A, however their precise source and also their roles in tumor development, evolution, and patient survival are debated. Currently, quantification of APOBEC3 expression changes in tumor cells is confounded by the ubiquitous expression of these enzymes in immune infiltrating cells. In this study, we used a novel quantitative biology approach to determine the expression profiles of APOBEC3 enzymes in breast tumor and tumor microenvironment cells from >1,000 patients. We combined diverse datasets including tumor/matched normal RNAseqs, tumor somatic mutations, cell line RNAseqs and mutations, estimates of tumor purities and immune cell compositions, and expression of purified cell populations to show that in breast cancer there is only a single APOBEC3 dysregulation process. This process is subtype-independent and is represented by APOBEC3B upregulation and and extreme APOBEC3C downregulation. Compared to all other tumor types, breast tumors are affected the most by this process. Citation Format: Hamid Hamidi, Azad Khosh, Hamzeh Rahimi, Diako Ebrahimi. Profiling of APOBEC3 dysregulation in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-13-05.