In this talk I will discuss our efforts to develop and apply single cell genome sequencing methods to study premalignant breast cancer invasion, as well as our efforts to build an atlas of normal cell types in human breast tissues. To study invasion in 10 patients with ductal carcinomas in situ (DCIS) premalignancies we developed a Topographic Single Cell Sequencing (TSCS) method that has spatial resolution to measure genomic copy number profiles in patients with synchronous DCIS-IDC tissues. Our data revealed a multi-clonal invasion model, in which genome evolution occurred within the ducts leading to the generation of multiple clones that co-migrated across the basement membrane to establish the invasive carcinomas. Our group is leading a collaborative effort to establish a human breast atlas of normal tissues using single cell RNA sequencing of 30 women. These data have identified major cell types including epithelial cells (luminal HR+, luminal secretory, basal), fibroblasts, adipocytes and endothelial cells (vascular, lymphatic) as well as immune cells (lymphocytes, myeloid). For each cell type, we have identified multiple (2-5) expression states that correspond to different biological functions. Collectively these data provide a ‘human genome’ reference of normal cell types and cell states in the human breast tissues to understand how the stromal and immune microenvironment is reprogrammed in breast cancers.

Citation Format: Nicholas E. Navin. Breast cancer evolution – Insights from single cell genomics [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr IA14.