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A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast.
- Source :
-
The EMBO journal [EMBO J] 2021 Jun 01; Vol. 40 (11), pp. e107333. Date of Electronic Publication: 2021 May 05. - Publication Year :
- 2021
-
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 <superscript>+/-</superscript> 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) <superscript>+</superscript> , HER2 <superscript>+</superscript> , and triple-negative breast cancers, revealed comparable diversity among cancer cells and a discrete subset of cycling cells. The transcriptomes of preneoplastic BRCA1 <superscript>+/-</superscript> tissue versus tumors highlighted global changes in the immune microenvironment. Within the tumor immune landscape, proliferative CD8 <superscript>+</superscript> T cells characterized triple-negative and HER2 <superscript>+</superscript> cancers but not ER <superscript>+</superscript> tumors, while all subtypes comprised cycling tumor-associated macrophages, thus invoking potentially different immunotherapy targets. Copy number analysis of paired ER <superscript>+</superscript> 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.<br /> (© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
- Subjects :
- Breast Neoplasms classification
Breast Neoplasms genetics
Breast Neoplasms pathology
CD8-Positive T-Lymphocytes metabolism
Carcinogenesis genetics
Carcinogenesis metabolism
Carcinogenesis pathology
Female
Gene Expression Profiling
Humans
Mammary Glands, Human cytology
Mammary Glands, Human pathology
RNA-Seq
Tumor Microenvironment
Breast Neoplasms metabolism
Gene Expression Regulation, Neoplastic
Genetic Heterogeneity
Mammary Glands, Human metabolism
Single-Cell Analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2075
- Volume :
- 40
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 33950524
- Full Text :
- https://doi.org/10.15252/embj.2020107333