Single-Cell RNA Sequencing Reveals the Cellular Origin and Evolution of Breast Cancer in <i>BRCA1</i> Mutation Carriers

Abstract The cell of origin and the development breast cancer are not fully elucidated in BRCA1 mutation carriers, especially for estrogen receptor (ER)–positive cancers. Here, we performed single-cell RNA sequencing (RNA-seq) on 82,122 cells isolated from tissues adjacent or prophylactic normal four carriers three noncarriers. Whole-exome was tumors carriers; validation, bulk RNA-seq eight additional 14 Correlation analyses suggested that cancers might originate luminal cells. aberrant progenitor with impaired differentiation were significantly increased compared These observations further validated by data carriers. suggest basal-like (ERneg) be expression TP53 decreased tissue which trigger basal/mesenchymal transition progenitors result tumor development. Furthermore, ERhigh mature Our study provides in-depth evidence regarding different subtypes Significance: Single-cell indicate progenitors,