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E-GEOD-69114 - Somatic cell fusions reveal extensive heterogeneity in basal-like breast cancer [RNA-Seq]

Status
Released on 10 June 2015, last updated on 12 June 2015
Organism
Homo sapiens
Samples (10)
Protocols (2)
Description
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. RNA-Seq in breast cancer cell-lines
Experiment type
RNA-seq of coding RNA 
Contacts
Kornelia Polyak, Reo Maruyama, Ying Su
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-69114.idf.txt
Sample and data relationshipE-GEOD-69114.sdrf.txt
Processed data (1)E-GEOD-69114.processed.1.zip
Links