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| Status |
Public on Jun 10, 2015 |
| Title |
Somatic cell fusions reveal extensive heterogeneity in basal-like breast cancer [SNP] |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
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| 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 |
We investigated the potential contribution of genetic factors to defining cell type-specific gene expression patterns by analyzing allelic inheritance based on Affymetrix SNP6.0 array hybridization of DNA from parental and fusion cells
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| Contributor(s) |
Polyak K, Gimelbrant A, Maruyama R |
| Citation(s) |
26051943 |
| Submission date |
Jul 17, 2012 |
| Last update date |
Nov 27, 2018 |
| 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) |
| GPL6801 |
[GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array |
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| Samples (19)
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| This SubSeries is part of SuperSeries: |
| GSE38548 |
Somatic cell fusions reveal extensive heterogeneity in basal-like breast cancer |
|
| Relations |
| BioProject |
PRJNA170834 |
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