Journal article
Chromosome Catastrophes Involve Replication Mechanisms Generating Complex Genomic Rearrangements
Cell (Cambridge), Vol.146(6), pp.889-903
2011
DOI: 10.1016/j.cell.2011.07.042
PMCID: PMC3242451
PMID: 21925314
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.
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► Constitutional CGR shares features with chromothripsis observed in cancer cells ► CGR can involve replication-based mechanisms ► Chromosome catastrophe can occur throughout an organism's life cycle
Patients with developmental disorders harbor major chromosomal rearrangements that resemble chromothripsis and are the result of DNA replication errors rather than chromosome shattering.
Details
- Title: Subtitle
- Chromosome Catastrophes Involve Replication Mechanisms Generating Complex Genomic Rearrangements
- Creators
- Pengfei Liu - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAAyelet Erez - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USASandesh C. Sreenath Nagamani - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAShweta U Dhar - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAKatarzyna E Kołodziejska - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAAvinash V Dharmadhikari - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAM. Lance Cooper - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAJoanna Wiszniewska - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAFeng Zhang - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAMarjorie A Withers - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USACarlos A Bacino - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USALuis Daniel Campos-Acevedo - Departamento de Genética, Hospital Universitario, Universidad Autónoma de Nuevo León, CP 64460 Monterrey, NL, MéxicoMauricio R Delgado - Texas Scottish Rite Hospital, Dallas, TX 75219, USADebra Freedenberg - Division of Medical Genetics, Vanderbilt University Medical Center, Nashville, TN 37232, USAAdolfo Garnica - St. Francis Hospital, Tulsa, OK 74136, USATheresa A Grebe - Division of Genetics and Metabolism, Phoenix Children's Hospital, Phoenix, AZ 85016, USADolores Hernández-Almaguer - Departamento de Genética, Hospital Universitario, Universidad Autónoma de Nuevo León, CP 64460 Monterrey, NL, MéxicoLaDonna Immken - ′Specially for Children, Austin, TX 78723, USASeema R Lalani - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAScott D McLean - Department of Pediatrics, San Antonio Military Medical Center, San Antonio, TX 78234, USAHope Northrup - Division of Medical Genetics, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030, USAFernando Scaglia - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USALane Strathearn - Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USAPamela Trapane - Children's Hospital of Wisconsin, Milwaukee, WI 53201, USASung-Hae L Kang - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAAnkita Patel - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USASau Wai Cheung - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAP.J Hastings - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAPaweł Stankiewicz - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAJames R Lupski - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAWeimin Bi - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.146(6), pp.889-903
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cell.2011.07.042
- PMID
- 21925314
- PMCID
- PMC3242451
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English
- Date published
- 2011
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Developmental and Behavioral Pediatrics; Neuroscience and Pharmacology
- Record Identifier
- 9984040258702771
Metrics
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