Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq

Mihriban Karaayvaz, Simona Cristea, Shawn M. Gillespie, Anoop P. Patel, Ravindra Mylvaganam, Christina C. Luo, Michelle C. Specht, Bradley E. Bernstein, Franziska Michor () and Leif W. Ellisen ()
Additional contact information
Mihriban Karaayvaz: Massachusetts General Hospital and Harvard Medical School
Simona Cristea: Dana-Farber Cancer Institute
Shawn M. Gillespie: Massachusetts General Hospital and Harvard Medical School
Anoop P. Patel: Massachusetts General Hospital and Harvard Medical School
Ravindra Mylvaganam: Massachusetts General Hospital and Harvard Medical School
Christina C. Luo: Massachusetts General Hospital and Harvard Medical School
Michelle C. Specht: Massachusetts General Hospital and Harvard Medical School
Bradley E. Bernstein: Massachusetts General Hospital and Harvard Medical School
Franziska Michor: Dana-Farber Cancer Institute
Leif W. Ellisen: Massachusetts General Hospital and Harvard Medical School

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by extensive intratumoral heterogeneity. To investigate the underlying biology, we conducted single-cell RNA-sequencing (scRNA-seq) of >1500 cells from six primary TNBC. Here, we show that intercellular heterogeneity of gene expression programs within each tumor is variable and largely correlates with clonality of inferred genomic copy number changes, suggesting that genotype drives the gene expression phenotype of individual subpopulations. Clustering of gene expression profiles identified distinct subgroups of malignant cells shared by multiple tumors, including a single subpopulation associated with multiple signatures of treatment resistance and metastasis, and characterized functionally by activation of glycosphingolipid metabolism and associated innate immunity pathways. A novel signature defining this subpopulation predicts long-term outcomes for TNBC patients in a large cohort. Collectively, this analysis reveals the functional heterogeneity and its association with genomic evolution in TNBC, and uncovers unanticipated biological principles dictating poor outcomes in this disease.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (12)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06052-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06052-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06052-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().