|
|||||
|
|
Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements |
|
| Authors: | Liu Pengfei Erez Ayelet Nagamani Sandesh C Sreenath Dhar Shweta U Ko?odziejska Katarzyna E Dharmadhikari Avinash V Cooper M Lance Wiszniewska Joanna Zhang Feng Withers Marjorie A Bacino Carlos A Campos-Acevedo Luis Daniel Delgado Mauricio R Freedenberg Debra Garnica Adolfo Grebe Theresa A Hernández-Almaguer Dolores Immken LaDonna Lalani Seema R McLean Scott D Northrup Hope Scaglia Fernando Strathearn Lane Trapane Pamela Kang Sung-Hae L Patel Ankita Cheung Sau Wai Hastings P J Stankiewicz Pawe? Lupski James R Bi Weimin |
| Institution: | 1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA 2 Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA 3 Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, USA 4 Texas Children's Hospital, Houston, TX 77030, USA 5 Departamento de Genética, Hospital Universitario, Universidad Autónoma de Nuevo León, CP 64460 Monterrey, NL, México 6 Texas Scottish Rite Hospital, Dallas, TX 75219, USA 7 Division of Medical Genetics, Vanderbilt University Medical Center, Nashville, TN 37232, USA 8 St. Francis Hospital, Tulsa, OK 74136, USA 9 Division of Genetics and Metabolism, Phoenix Children's Hospital, Phoenix, AZ 85016, USA 10 ′Specially for Children, Austin, TX 78723, USA 11 Department of Pediatrics, San Antonio Military Medical Center, San Antonio, TX 78234, USA 12 Division of Medical Genetics, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030, USA 13 Children's Hospital of Wisconsin, Milwaukee, WI 53201, USA |
| 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. |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |