Single-Cell Expression Analysis of Ductal Carcinoma In Situ Identifies Complex Genotypic-Phenotypic Relationships Altering Epithelial Composition.

ABSTRACT: Ductal carcinoma in situ (DCIS) is a risk factor for subsequent invasive breast cancer (IBC). To identify events in DCIS that lead to invasive cancer, we performed single-cell RNA sequencing on DCIS lesions and matched normal breast tissue. Inferred copy-number variation was used to identify neoplastic epithelial cells from clinical specimens, which contained a mixture of DCIS and normal ducts. Phylogenetic analysis demonstrated intratumoral clonal heterogeneity that was associated with significant gene expression differences. Classification of epithelial cells into mammary cell states revealed that subclones contained a mixture of cell states, suggesting an ongoing pattern of differentiation after neoplastic transformation. Cell state proportions were significantly different based on estr

SUBMITTER: Qin X 

PROVIDER: S-EPMC12167932 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature