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| Status |
Public on Jun 10, 2015 |
| Title |
Somatic cell fusions reveal extensive heterogeneity in basal-like breast cancer [methylation450] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
|
| 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 |
Bisulphite converted DNA from 20 breast cancer cell lines were hybridized to the Illumina Infinium HumanMethylation450 BeadChip.
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| Contributor(s) |
Polyak K, Maruyama R, Fackler MJ |
| Citation(s) |
26051943 |
| Submission date |
Apr 07, 2015 |
| Last update date |
Mar 22, 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
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| Lab |
Polyak
|
| Street address |
450 Brookline Ave
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE38548 |
Somatic cell fusions reveal extensive heterogeneity in basal-like breast cancer |
|
| Relations |
| BioProject |
PRJNA280641 |
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