A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast
- Author(s)
- Pal, B; Chen, Y; Vaillant, F; Capaldo, BD; Joyce, R; Song, X; Bryant, VL; Penington, JS; Di Stefano, L; Tubau Ribera, N; Wilcox, S; Mann, GB; kConFab Investigators,; Papenfuss, AT; Lindeman, GJ; Smyth, GK; Visvader, JE;
- Details
- Publication Year 2021-05-05,Volume 40,Issue #11,Page e107333
- Journal Title
- EMBO Journal
- Abstract
- To examine global changes in breast heterogeneity across different states, we determined the single-cell transcriptomes of > 340,000 cells encompassing normal breast, preneoplastic BRCA1(+/-) tissue, the major breast cancer subtypes, and pairs of tumors and involved lymph nodes. Elucidation of the normal breast microenvironment revealed striking changes in the stroma of post-menopausal women. Single-cell profiling of 34 treatment-naive primary tumors, including estrogen receptor (ER)(+) , HER2(+) , and triple-negative breast cancers, revealed comparable diversity among cancer cells and a discrete subset of cycling cells. The transcriptomes of preneoplastic BRCA1(+/-) tissue versus tumors highlighted global changes in the immune microenvironment. Within the tumor immune landscape, proliferative CD8(+) T cells characterized triple-negative and HER2(+) cancers but not ER(+) tumors, while all subtypes comprised cycling tumor-associated macrophages, thus invoking potentially different immunotherapy targets. Copy number analysis of paired ER(+) tumors and lymph nodes indicated seeding by genetically distinct clones or mass migration of primary tumor cells into axillary lymph nodes. This large-scale integration of patient samples provides a high-resolution map of cell diversity in normal and cancerous human breast.
- Publisher
- Embo Press
- Keywords
- BRCA1 carriers; LN metastasis; breast cancer; microenvironment; single-cell RNA-seq
- Research Division(s)
- Cancer Biology And Stem Cells; Advanced Technology And Biology; Bioinformatics; Immunology
- PubMed ID
- 33950524
- Publisher's Version
- https://doi.org/10.15252/embj.2020107333
- Open Access at Publisher's Site
https://doi.org/10.15252/embj.2020107333- NHMRC Grants
- NHMRC/1100807, NHMRC/1113133, NHMRC/1078730, NHMRC/1058892, NHMRC/1037230, NHMRC/1102742,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-05-11 04:12:13
Last Modified: 2021-07-06 11:06:08