Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements

Pengfei Liu, Ayelet Erez, Sandesh C.Sreenath Nagamani, Shweta U. Dhar, Katarzyna E. Kołodziejska, Avinash V. Dharmadhikari, M. Lance Cooper, Joanna Wiszniewska, Feng Zhang, Marjorie A. Withers, Carlos A. Bacino, Luis Daniel Campos-Acevedo, Mauricio R. Delgado, Debra Freedenberg, Adolfo Garnica, Theresa A. Grebe, Dolores Hernández-Almaguer, Ladonna Immken, Seema R. Lalani, Scott D. McLeanHope Northrup, Fernando Scaglia, Lane Strathearn, Pamela Trapane, Sung Hae L. Kang, Ankita Patel, Sau Wai Cheung, P. J. Hastings, Paweł Stankiewicz, James R. Lupski, Weimin Bi

Research output: Contribution to journalArticlepeer-review

348 Scopus citations


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.

Original languageEnglish
Pages (from-to)889-903
Number of pages15
Issue number6
StatePublished - 16 Sep 2011
Externally publishedYes


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