title: Chromothripsis: potential origin in gametogenesis and preimplantation cell divisions. A review.
abstract: OBJECTIVE
  To review the discovery of chromothripsis and analyze its impact on human reproduction.
  
  
  METHODS
  Database and literature analysis.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Carriers of massive and complex chromosomal rearrangements.
  
  
  METHODS
  Cytogenetic analysis and molecular testing (fluorescence in situ hybridization, microarray, whole-genome sequencing).
  
  
  METHODS
  Chromothripsis occurrence in human gametes and preimplantation embryos, with regard to the potential causative mechanisms described in literature.
  
  
  RESULTS
  Databases were searched for the literature published up to March 2014. Chromothripsis is characterized by the shattering of one (or a few) chromosome segments followed by a haphazard reassembly of the fragments generated, arising through a single initial catastrophic event. Several mechanisms involving abortive apoptosis, telomere erosion, mitotic errors, micronuclei formation, and p53 inactivation might cause chromothripsis. The remarkable point is that all these plausible mechanisms have been identified in the field of human reproduction as causal factors for reproductive failures and the genesis of chromosomal abnormalities. Specific features of gametogenesis and early embryonic development such as the weakness of cell cycle and mitosis checkpoints and the rapid kinetics of division in germ cells and early cleavage embryos may contribute to the emergence of chromothripsis.
  
  
  CONCLUSIONS
  The discovery of this new class of massive chromosomal rearrangement has deeply modified our understanding on the genesis of complex genomic rearrangements. Data presented in this review support the assumption that chromothripsis could operate in human germlines and during early embryonic development. Chromothripsis might arise more frequently than previously thought in both gametogenesis and early human embryogenesis.
authors.affiliation: Laboratory of Chromosomal Genetics, Department of Medical Genetics, Arnaud de Villeneuve Hospital, Montpellier CHRU, Montpellier, France; INSERM Unit Plasticity of the Genome and Aging, Institute of Functional Genomics, Montpellier, France. Electronic address: f-pellestor@chu-montpellier.fr.
authors.forename: Franck
authors.initials: F
authors.lastname: Pellestor
authors.affiliation: Laboratory of Chromosomal Genetics, Department of Medical Genetics, Arnaud de Villeneuve Hospital, Montpellier CHRU, Montpellier, France; INSERM Unit Plasticity of the Genome and Aging, Institute of Functional Genomics, Montpellier, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Gatinois
authors.affiliation: Laboratory of Chromosomal Genetics, Department of Medical Genetics, Arnaud de Villeneuve Hospital, Montpellier CHRU, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Puechberty
authors.affiliation: Laboratory of Chromosomal Genetics, Department of Medical Genetics, Arnaud de Villeneuve Hospital, Montpellier CHRU, Montpellier, France.
authors.forename: David
authors.initials: D
authors.lastname: Geneviève
authors.affiliation: Laboratory of Chromosomal Genetics, Department of Medical Genetics, Arnaud de Villeneuve Hospital, Montpellier CHRU, Montpellier, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Lefort
mesh_terms: D001755:Blastocyst / Q000187:drug effects*; D002455:Cell Division; D043171:Chromosomal Instability / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced*; D056905:Chromosome Breakpoints / Q000187:drug effects; D025063:Chromosome Disorders / Q000235:genetics; D049914:DNA Repair-Deficiency Disorders / Q000235:genetics; D005718:Gametogenesis / Q000187:drug effects; D015321:Gene Rearrangement / Q000187:drug effects*; D015894:Genome, Human; D005854:Germ Cells / Q000187:drug effects*; D006801:Humans
keywords: Chromothripsis; embryo; fertilization; gametogenesis; massive chromosomal rearrangement