Chromosomal instability as a source of genomic plasticity.

Chromosomal instability (CIN) is a hallmark of the most aggressive malignancies. Features of these tumors include complex genomic rearrangements, the presence of mis-segregated chromosomes in micronuclei, and extrachromosomal DNA (ecDNA) formation. Here, we review the development of CIN, and examine CIN in the context of cancer evolution, tumor genomic evolution, and therapeutic resistance. We also discuss the role of whole-genome duplications, breakage-fusion-bridge cycles, ecDNA or double minutes in gene amplification promoting tumor evolution.