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| Status |
Public on Aug 11, 2018 |
| Title |
Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by extensive intratumoral heterogeneity. To investigate the underlying biology, we conduct single-cell RNA- sequencing (scRNA-seq) of >1500 cells from six primary TNBC. Intercellular heterogeneity of gene expression programs within each tumor was variable and largely correlated 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 was predictive of long-term outcomes for TNBC patients in a large patient 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.
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| |
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| Overall design |
Single cell RNA sequencing of 1,534 cells in six fresh triple negative breast cancer tumors.
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| |
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| Contributor(s) |
Cristea S |
| Citation(s) |
30181541 |
| Submission date |
Aug 10, 2018 |
| Last update date |
Feb 21, 2019 |
| Contact name |
Simona Cristea |
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Biostatistics and Computational Biology
|
| Street address |
450 Brookline Ave.
|
| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
|
| Samples (1534)
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| This SubSeries is part of SuperSeries: |
| GSE118390 |
Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq |
|
| Relations |
| BioProject |
PRJNA485429 |
| SRA |
SRP157044 |
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