The Diverse Effects of Complex Chromosome Rearrangements and Chromothripsis in Cancer Development

Abstract

In recent years, enormous progress has been made with respect to the identification of somatic mutations that contribute to cancer development. Mutation types range from small substitutions to large structural genomic rearrangements, including complex reshuffling of the genome. Sets of mutations in individual cancer genomes may show specific signatures, which can be provoked by both exogenous and endogenous forces. One of the most remarkable mutation patterns observed in human cancers involve massive rearrangement of just a few chromosomal regions. This phenomenon has been termed chromothripsis and appears widespread in a multitude of cancer types. Chromothripsis provides a way for cancer to rapidly evolve through a one-off massive change in genome structure as opposed to a gradual process of mutation and selection. This chapter focuses on the origin, prevalence and impact of chromothripsis and related complex genomic rearrangements during cancer development.

Keywords: Chromosomal rearrangement; Chromothripsis; Mutation signatures; Next-generation paired-end sequencing.