Single-cell transcriptomics and whole-genome sequencing reveal the tumor landscape in breast carcinosarcoma

Breast carcinosarcoma is a rare and highly aggressive subtype of metaplastic breast carcinoma. It is typically negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), and displays greater invasiveness and metastatic potential than triple-negative breast cancer (TNBC). This exploratory single-case study analyzed one individual breast carcinosarcoma sample via single-cell RNA sequencing, which revealed that the tumor was predominantly composed of epithelial cells and fibroblasts, with four distinct subpopulations identified for each cell type. In this case, critical crosstalk between malignant epithelial cells and mesenchymal cells may be mediated by the LAMININ, MK, and APP signaling pathways. Comparative analysis of single-cell sequencing data from this sample with publicly available TNBC single-cell datasets revealed notable differences in cellular composition between this breast carcinosarcoma case and TNBC samples. Whole-genome sequencing of the sample identified complex genomic alterations, including potential germline susceptibility-related candidate genes and candidate driver mutations associated with the tumor in this case. This study presents single-cell transcriptomic and whole-genomic profiling data for a single case of breast carcinosarcoma, deepens understanding of the biological characteristics of this tumor in the studied case, and provides a novel exploratory resource for investigating the heterogeneity of breast carcinosarcoma.