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| Status |
Public on Jun 10, 2015 |
| Title |
Somatic cell fusions reveal extensive heterogeneity in basal-like breast cancer [DGE] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and it is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells is sufficient to induce luminal-to-basal phenotypic switch implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells.
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|
| Overall design |
Digital gene expression profiles of basal-like, luminal and their heterofusion cells were generated by deep sequencing, using Helicos HeliScope.
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| Contributor(s) |
Polyak K, Maruyama R, Su Y, Bloushtain-Qimron N |
| Citation(s) |
26051943 |
| Submission date |
Jun 18, 2012 |
| Last update date |
May 15, 2019 |
| 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 |
| |
|
| Platforms (1) |
| GPL14761 |
Helicos HeliScope (Homo sapiens) |
|
| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE38548 |
Somatic cell fusions reveal extensive heterogeneity in basal-like breast cancer |
|
| Relations |
| SRA |
SRP013812 |
| BioProject |
PRJNA170832 |
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