Chromothripsis: how does such a catastrophic event impact human reproduction?

Hum Reprod. 2014 Mar;29(3):388-93. doi: 10.1093/humrep/deu003. Epub 2014 Jan 21.


The recent discovery of a new kind of massive chromosomal rearrangement, baptized chromothripsis (chromo for chromosomes, thripsis for shattering into pieces), greatly modifies our understanding of molecular mechanisms implicated in the repair of DNA damage and the genesis of complex chromosomal rearrangements. Initially described in cancers, and then in constitutional rearrangements, chromothripsis is characterized by the shattering of one (or a few) chromosome(s) segments followed by a chaotic reassembly of the chromosomal fragments, occurring during one unique cellular event. The diversity and the high complexity of chromothripsis events raise questions about their origin, their ties to chromosome instability and their impact in pathology. Several causative mechanisms, involving abortive apoptosis, telomere erosion, mitotic errors, micronuclei formation and p53 inactivation, have been proposed. The remarkable point is that all these mechanisms have been identified in the field of human reproduction as causal factors for reproductive failures and chromosomal abnormalities. Consequently, it seems important to consider this unexpected catastrophic phenomenon in the context of fertilization and early embryonic development in order to discuss its potential impact on human reproduction.

Keywords: chromosomal rearrangement; chromothripsis; embryo; fertilization; genomic instability.

MeSH terms

  • Chromosomal Instability*
  • Chromosome Aberrations*
  • Chromosome Disorders / genetics*
  • DNA Repair / physiology
  • DNA Replication / genetics
  • Genome, Human*
  • Humans
  • Reproduction / genetics*