Regulation of 3D Organization and Its Role in Cancer Biology

Three-dimensional (3D) genomics is the frontier field in the post-genomics era, its foremost content is the relationship between chromatin spatial conformation and regulation of gene transcription. Cancer biology is a complex system resulting from genetic alterations in key tumor oncogenes and suppressor genes for cell proliferation, DNA replication, cell differentiation, and homeostatic functions. Although scientific research in recent decades has revealed how the genome sequence is mutated in many cancers, high-order chromosomal structures involved in the development and fate of cancer cells represent a crucial but rarely explored aspect of cancer genomics. Hence, dissection of the 3D genome conformation of cancer helps understand the unique epigenetic patterns and gene regulation processes that distinguish cancer biology from normal physiological states. In recent years, research in tumor 3D genomics has grown quickly. With the rapid progress of 3D genomics technology, we can now better determine the relationship between cancer pathogenesis and the chromatin structure of cancer cells. It is becoming increasingly explicit that changes in 3D chromatin structure play a vital role in controlling oncogene transcription. This review focuses on the relationships between tumor gene expression regulation, tumor 3D chromatin structure, and cancer phenotypic plasticity. Furthermore, based on the functional consequences of spatial disorganization in the cancer genome, we look forward to the clinical application prospects of 3D genomic biomarkers.