Single Cell Expression Analysis of Ductal Carcinoma in Situ Identifies Alterations in Epithelial Integrity

The defining characteristic of ductal carcinoma in situ (DCIS) is neoplastic epithelial growth within a duct surrounded by an intact basement membrane (BM) whereas invasive breast cancer (IBC) is defined by tumor cell extravasation associated with loss of the intact BM. To understand mechanisms underlying the development of DCIS, we performed single-cell RNA-sequencing (scRNA-seq) on DCIS and synchronous normal tissue. We identified neoplastic epithelial cells by inferring copy number variations from RNA expression and then classified cells using previously defined phenotypes from normal human breast epithelium. We identify an increase in luminal cells in DCIS and a concomitant decrease in basal cells, which are a significant source of BM gene expression. We hypothesize that the reduction of the relative abundance of basal cells reduces the integrity of the BM that can result in the invasive phenotype. ### Competing Interest Statement RBW has consulted for IonPath Inc.