Abstract P2-18-01: Matched Single-Cell RNA-seq and Single-Cell ATAC-seq of Male Breast Cancers Nominate Salient Cancer-Specific Enhancers

Abstract Although male breast cancer accounts for less than 1% of all breast cancer cases, overall survival is worse for men compared to women. This is due, in part, to the older age of patients at the time of diagnosis and the increased presence of comorbidities in the male population. While male breast cancer presents with similarities to certain female breast cancers, the paucity of data available on male breast cancer makes it difficult to establish targeted therapies, and to date, most male breast cancers are treated according to the standards in place for female breast cancer. Thus, investigating the transcriptional and epigenetic landscape of male breast cancer with improved resolution is crucial for understanding the tumor heterogeneity of this rare cancer type and can lead to the discovery of new therapeutic targets. In this study, we present matched transcriptional (scRNA-seq) and epigenetic (scATAC-seq) profiles of two male breast cancer tumors at single-cell resolution. Using scRNA-seq, we determine differentially expressed genes between male and female breast cancer tumors, specifically in the malignant cell populations, and highlight several genes that may have therapeutic implications within male breast cancer. We then leverage the scATAC-seq data to link variation in chromatin accessibility to changes in gene expression and show that certain highly expressed genes in the tumor-epithelial cells of male breast tumors are linked to highly active enhancer elements that drive their expression. Finally, we examine transcription factor motifs in the tumor-epithelial regulatory regions of male breast cancer tumors to further investigate the regulatory logic of these cell types. Overall, this dataset exposes clinically relevant regulatory networks in male breast tumors, providing a useful resource to the field of breast oncology that expands on the current knowledge of male breast cancer genetics. Citation Format: Kamila Wisniewska, Hyunsoo Kim, Matthew J. Regner, Philip Spanheimer, Hector L. Franco. Matched Single-Cell RNA-seq and Single-Cell ATAC-seq of Male Breast Cancers Nominate Salient Cancer-Specific Enhancers [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 P2-18-01.