Rebuilding Chromosomes After Catastrophe: Emerging Mechanisms of Chromothripsis

Trends Cell Biol. 2017 Dec;27(12):917-930. doi: 10.1016/j.tcb.2017.08.005. Epub 2017 Sep 9.


Cancer genome sequencing has identified chromothripsis, a complex class of structural genomic rearrangements involving the apparent shattering of an individual chromosome into tens to hundreds of fragments. An initial error during mitosis, producing either chromosome mis-segregation into a micronucleus or chromatin bridge interconnecting two daughter cells, can trigger the catastrophic pulverization of the spatially isolated chromosome. The resultant chromosomal fragments are religated in random order by DNA double-strand break repair during the subsequent interphase. Chromothripsis scars the cancer genome with localized DNA rearrangements that frequently generate extensive copy number alterations, oncogenic gene fusion products, and/or tumor suppressor gene inactivation. Here we review emerging mechanisms underlying chromothripsis with a focus on the contribution of cell division errors caused by centromere dysfunction.

Keywords: DNA repair; chromosome rearrangements; chromothripsis; genomic instability; micronuclei; mitosis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Centromere / genetics
  • Centromere / metabolism
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromothripsis*
  • DNA / genetics
  • DNA / metabolism
  • DNA Breaks, Double-Stranded*
  • DNA Repair*
  • Genome, Human / genetics*
  • Humans
  • Mitosis / genetics
  • Models, Genetic


  • Chromatin
  • DNA