Patterns and mechanisms of structural variations in human cancer

Next-generation sequencing technology has enabled the comprehensive detection of genomic alterations in human somatic cells, including point mutations, chromosomal rearrangements, and structural variations (SVs). Using sophisticated bioinformatics algorithms, unbiased catalogs of SVs are emerging from thousands of human cancer genomes for the first time. Via careful examination of SV breakpoints at single-nucleotide resolution as well as local DNA copy number changes, diverse patterns of genomic rearrangements are being revealed. These “SV signatures” provide deep insight into the mutational processes that have shaped genome changes in human somatic cells. This review summarizes the characteristics of recently identified complex SVs, including chromothripsis, chromoplexy, microhomology-mediated breakage-induced replication (MMBIR), and others, to provide a holistic snapshot of the current knowledge on genomic rearrangements in somatic cells. Advances in sequencing technologies enable detailed analyses of large genomic alterations, known as structural variations (SV), in human cancer cells. Young Seok Ju and Kijong Yi at the Korea Advanced Institute of Science and Technology in Daejeon, review current knowledge on SV patterns in human cancer genomes and the molecular processes through which they arise. In addition to the loss, gain and reshuffling of large nuclear genetic sequences, cancer cells can also acquire external DNA sequences from viruses, mitochondria, or bacteria that alter gene expression levels or affect gene function. Understanding how these SV drive cancer initiation and progression will not only shed light on the organization and function of the genome, but also provide new opportunities for drug discovery and patient screening that will facilitate a more personalized treatment approach.