Processes shaping cancer genomes - From mitotic defects to chromosomal rearrangements

Sequencing of cancer genomes revealed a rich landscape of somatic single nucleotide variants, structural changes of chromosomes, as well as chromosomal copy number alterations. These chromosome changes are highly variable, and simple translocations, deletions or duplications have been identified, as well as complex events that likely arise through activity of several interconnected processes. Comparison of the cancer genome sequencing data with our knowledge about processes important for maintenance of genome stability, namely DNA replication, repair and chromosome segregation, provides insights into the mechanisms that may give rise to complex chromosomal patterns, such as chromothripsis, a complex form of multiple focal chromosome rearrangements. In addition, observations gained from model systems that recapitulate the rearrangements patterns under defined experimental conditions suggest that mitotic errors and defective DNA replication and repair contribute to their formation. Here, we review the molecular mechanisms that contribute to formation of chromosomal aberrations observed in cancer genomes.