title: Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements.
abstract: Complex genomic rearrangements (CGRs) consisting of two or more breakpoint junctions have been observed in genomic disorders. Recently, a chromosome catastrophe phenomenon termed chromothripsis, in which numerous genomic rearrangements are apparently acquired in one single catastrophic event, was described in multiple cancers. Here, we show that constitutionally acquired CGRs share similarities with cancer chromothripsis. In the 17 CGR cases investigated, we observed localization and multiple copy number changes including deletions, duplications, and/or triplications, as well as extensive translocations and inversions. Genomic rearrangements involved varied in size and complexities; in one case, array comparative genomic hybridization revealed 18 copy number changes. Breakpoint sequencing identified characteristic features, including small templated insertions at breakpoints and microhomology at breakpoint junctions, which have been attributed to replicative processes. The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism's life cycle.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.forename: Ayelet
authors.initials: A
authors.lastname: Erez
authors.forename: Sandesh C Sreenath
authors.initials: SC
authors.lastname: Nagamani
authors.forename: Shweta U
authors.initials: SU
authors.lastname: Dhar
authors.forename: Katarzyna E
authors.initials: KE
authors.lastname: Kołodziejska
authors.forename: Avinash V
authors.initials: AV
authors.lastname: Dharmadhikari
authors.forename: M Lance
authors.initials: ML
authors.lastname: Cooper
authors.forename: Joanna
authors.initials: J
authors.lastname: Wiszniewska
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Marjorie A
authors.initials: MA
authors.lastname: Withers
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bacino
authors.forename: Luis Daniel
authors.initials: LD
authors.lastname: Campos-Acevedo
authors.forename: Mauricio R
authors.initials: MR
authors.lastname: Delgado
authors.forename: Debra
authors.initials: D
authors.lastname: Freedenberg
authors.forename: Adolfo
authors.initials: A
authors.lastname: Garnica
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Grebe
authors.forename: Dolores
authors.initials: D
authors.lastname: Hernández-Almaguer
authors.forename: LaDonna
authors.initials: L
authors.lastname: Immken
authors.forename: Seema R
authors.initials: SR
authors.lastname: Lalani
authors.forename: Scott D
authors.initials: SD
authors.lastname: McLean
authors.forename: Hope
authors.initials: H
authors.lastname: Northrup
authors.forename: Fernando
authors.initials: F
authors.lastname: Scaglia
authors.forename: Lane
authors.initials: L
authors.lastname: Strathearn
authors.forename: Pamela
authors.initials: P
authors.lastname: Trapane
authors.forename: Sung-Hae L
authors.initials: SH
authors.lastname: Kang
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: P J
authors.initials: PJ
authors.lastname: Hastings
authors.forename: Paweł
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Weimin
authors.initials: W
authors.lastname: Bi
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D055028:Comparative Genomic Hybridization; D004260:DNA Repair; D004261:DNA Replication; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*