Origins and consequences of oncogenic 3D chromatin remodelling

The 3D structure of chromatin is altered in cancer. In healthy cells, the genome is folded into functional 3D structural elements, including chromosomes, chromatin compartments, domains and loops. Cancer-associated alterations can modify each of these structural elements and, sometimes, their oncogenic capacity can be explained only when accounting for their effect on chromatin 3D conformation. In this Review, we discuss multiple lines of evidence demonstrating the impact of genetic and epigenetic alterations on chromatin structural elements, and the potential for chromatin 3D architecture to favour the acquisition of specific alterations. As a result, chromatin 3D remodelling emerges as both a cause and a consequence of oncogenic alterations. Finally, we highlight outstanding questions and opportunities related to the role of chromatin 3D heterogeneity in cancer, and the possibility of exploiting chromatin 3D conformation for diagnosis and therapy. Overall, chromatin 3D conformation integrates information from multiple molecular features, and thus it may represent a key to decoding cancer phenotypes.