Spatial genome architecture and the emergence of malignancy

Author:

Danieli Adi1,Papantonis Argyris1

Affiliation:

1. Institute of Pathology, University Medical Center Göttingen, 37075 Göttingen, Germany

Abstract

Abstract 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 the disruption of topologically associating domains, switching between active and inactive compartments, rewiring of promoter–enhancer interactions in malignancy as well as the effects of single nucleotide polymorphisms 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.

Funder

Deutsche Forschungsgemeinschaft

Publisher

Oxford University Press (OUP)

Subject

Genetics(clinical),Genetics,Molecular Biology,General Medicine

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