[Perspective] The oncogene makes its escape
Far from a random tangle, cellular DNA is packed into the nucleus with astounding precision. Indeed, there is growing appreciation for how the three-dimensional (3D) organization of the genome contributes to controlling gene expression. For instance, loops of DNA called insulated neighborhoods can protect small groups of genes from silencing or activation (1). If cancer can result from dysregulation of gene expression (2), then an enticing hypothesis is that disrupting insulated neighborhoods may lead to increased transcription of cancer genes. On page 1454 of this issue, Hnisz et al. (3) use tumor-derived sequencing data and targeted deletions in cells to show that disruption of insulated neighborhoods leads to activation of proto-oncogenes—genes with the potential to cause cancer. These findings strongly support disruption of chromatin structure as causally linked to tumorigenesis, and suggest that such disruptions may be the hidden culprit driving many tumors. Authors: Jeremiah Wala, Rameen Beroukhim