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| Status |
Public on Nov 09, 2023 |
| Title |
Epigenetic heterogeneity and transcriptional drivers of triple-negative breast cancer (H3K27ac cell lines ChIP-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Triple-negative breast cancer (TNBC) is a heterogeneous disease with limited treatment options. To characterize TNBC heterogeneity and treatment response, we combined functional and molecular profiling with computational analysis tools. Using these approaches, we defined transcriptional, epigenetic, and metabolic subtypes, and identified subtype-driving super-enhancers. Single cell RNA sequencing analyses revealed relative homogeneity of the three major transcriptional subtypes (luminal, basal and mesenchymal) within tumors. We found that mesenchymal TNBCs are more similar to mesenchymal neuroblastoma and rhabdoid tumors than to other TNBC subtypes, and the PRRX1 transcription factor serves as a key driver of these tumors. By directly regulating the transcription of mesenchymal genes, PRRX1 is sufficient for inducing the mesenchymal subtype but is not required for its maintenance.
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| Overall design |
H3K27ac ChIP-seq of 30 TNBC cell lines
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| |
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| Contributor(s) |
Jovanović B, Temko D, Michor F, Polyak K |
| Citation(s) |
38100350 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P01 CA250959 |
New therapeutic vulnerabilities in breast cancer |
DANA-FARBER CANCER INSTITUTE |
Kornelia Polyak |
| R35 CA197623 |
Targeting intratumor heterogeneity in breast cancer |
DANA-FARBER CANCER INSTITUTE |
Kornelia Polyak |
| U54 CA193461 |
Evolution and Treatment Response of Brain, Breast, and Hematologic Malignancies |
DANA-FARBER CANCER INSTITUTE |
Franziska Michor |
| P50 CA168504 |
Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer |
DANA-FARBER CANCER INSTITUTE |
Kornelia Polyak |
| R01 CA251599 |
Targeting of a Major Immune Evasion Pathway in Triple-negative Breast Cancer |
DANA-FARBER CANCER INSTITUTE |
Kai W Wucherpfennig |
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| |
| Submission date |
May 11, 2022 |
| Last update date |
Dec 25, 2023 |
| Contact name |
Kornelia Polyak |
| E-mail(s) |
kornelia_polyak@dfci.harvard.edu
|
| Phone |
617-632-2106
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Medical Oncology
|
| Lab |
Polyak
|
| Street address |
450 Brookline Ave
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (60)
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| This SubSeries is part of SuperSeries: |
| GSE202776 |
Epigenetic heterogeneity and transcriptional drivers of triple-negative breast cancer |
|
| Relations |
| BioProject |
PRJNA837232 |
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