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Activation of proto-oncogenes by disruption of chromosome neighborhoods [ChIP-Seq]

GSE68976 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 10 samples Submitted 2015/05/28 Platform GPL11154Platform GPL16791
Summary
Mutations such as gene fusion, translocation and focal amplification are a frequent cause of proto-oncogene activation during tumorigenesis, but such mutations do not explain all cases of proto-oncogene activation. Here we show that disruption of local chromosome conformation can also activate proto-oncogenes in human cells. We mapped chromosome structures in T-cell acute lymphoblastic leukemia (T-ALL), and found that active oncogenes and silent proto-oncogenes generally occur within insulated neighborhoods formed by the looping of two interacting CTCF sites co-occupied by cohesin. Recurrent microdeletions frequently overlap neighborhood boundary sites in T-ALL genomes, and we demonstrate that site-specific perturbation of loop boundaries is sufficient to activate the respective proto-oncogenes in non-malignant cells. We found somatic genomic rearrangements affecting loop boundaries in many cancers. These results suggest that chromosome structural organization is fundamental to identify functional somatic alterations in cancer genomes.
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Also filed as BioProject PRJNA284251 and SRA study SRP058436. Searching any of these in the dataset finder brings you back here.

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