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Nature communications
05 05, 2017;8 15081.

Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer.

Woosung Chung, Hye Hyeon Eum, Hae-Ock Lee, Kyung-Min Lee, Han-Byoel Lee, Kyu-Tae Kim, Han Suk Ryu, Sangmin Kim, Jeong Eon Lee, Yeon Hee Park, Zhengyan Kan, Wonshik Han, Woong-Yang Park
Author Information
  1. Woosung Chung: Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea.
  2. Hye Hyeon Eum: Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea.
  3. Hae-Ock Lee: Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea.
  4. Kyung-Min Lee: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
  5. Han-Byoel Lee: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
  6. Kyu-Tae Kim: Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea.
  7. Han Suk Ryu: Department of Pathology, Seoul National University College of Medicine, Seoul 03080, South Korea.
  8. Sangmin Kim: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
  9. Jeong Eon Lee: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
  10. Yeon Hee Park: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul 06351, Korea.
  11. Zhengyan Kan: Oncology Research, Pfizer Inc., San Diego, California 92121, USA.
  12. Wonshik Han: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
  13. Woong-Yang Park: Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea. ORCID
PMID: 28474673 DOI: 10.1038/ncomms15081

Abstract

Single-cell transcriptome profiling of tumour tissue isolates allows the characterization of heterogeneous tumour cells along with neighbouring stromal and immune cells. Here we adopt this powerful approach to breast cancer and analyse 515 cells from 11 patients. Inferred copy number variations from the single-cell RNA-seq data separate carcinoma cells from non-cancer cells. At a single-cell resolution, carcinoma cells display common signatures within the tumour as well as intratumoral heterogeneity regarding breast cancer subtype and crucial cancer-related pathways. Most of the non-cancer cells are immune cells, with three distinct clusters of T lymphocytes, B lymphocytes and macrophages. T lymphocytes and macrophages both display immunosuppressive characteristics: T cells with a regulatory or an exhausted phenotype and macrophages with an M2 phenotype. These results illustrate that the breast cancer transcriptome has a wide range of intratumoral heterogeneity, which is shaped by the tumour cells and immune cells in the surrounding microenvironment.

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MeSH Term

B-Lymphocytes
Breast Neoplasms
Carcinoma, Ductal, Breast
DNA Copy Number Variations
Female
Gene Expression Profiling
Humans
Lymph Nodes
Lymphocytes, Tumor-Infiltrating
Macrophages
Receptor, ErbB-2
Receptors, Estrogen
Receptors, Progesterone
Sequence Analysis, RNA
Single-Cell Analysis
T-Lymphocytes
Triple Negative Breast Neoplasms
Tumor Microenvironment
Exome Sequencing

Chemicals

Receptors, Estrogen
Receptors, Progesterone
ERBB2 protein, human
Receptor, ErbB-2
Journal Article Research Support, Non-U.S. Gov't

Links to CNCB-NGDC Resources

GEN: GEND000201 (Single cell RNA sequencing of primary breast cancer.)
GEN: GEND000351 (Single cell RNA sequencing of primary breast cancer.)

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