Spatial genome architecture and the emergence of malignancy.

Human chromosomes are large spatially- and hierarchically-structured entities, the integrity of which needs to be preserved throughout the lifespan of the cell and in conjunction with cell cycle progression. Preservation of chromosomal structure is important for proper deployment of cell type-specific gene expression programs. Thus, aberrations in the integrity and structure of chromosomes will predictably lead to disease, including cancer. Here, we provide an updated standpoint with respect to chromatin misfolding and the emergence of various cancer types. We discuss recent studies implicating disruption of topologically-associating domains (TADs), switching between active and inactive compartments, rewiring of promoter-enhancer interactions in malignancy, as well as the effects of single nucleotide polymorphisms (SNPs) in non-coding regions involved in long-range regulatory interactions. In light of these findings, we argue that chromosome conformation studies may now also be useful for patient diagnosis and drug target discovery.