Chromosome Catastrophes Involve Replication Mechanisms Generating Complex Genomic Rearrangements

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• 作者：Pengfei Liu¹ ;   ; ¹⁶ ; Ayelet Erez¹ ;   ; ⁴ ;   ; ¹⁶ ; Sandesh  ; C.  ; Sreenath Nagamani¹ ;   ; ⁴ ; Shweta  ; U. Dhar¹ ;   ; ⁴ ; Katarzyna  ; E. Koł ; odziejska¹ ; Avinash  ; V. Dharmadhikari¹ ; M.  ; Lance Cooper¹ ; Joanna Wiszniewska¹ ; Feng Zhang¹ ;   ; ¹⁴ ; Marjorie  ; A. Withers¹ ; Carlos  ; A. Bacino¹ ;   ; ⁴ ; Luis  ; Daniel Campos-Acevedo⁵ ; Mauricio  ; R. Delgado⁶ ; Debra Freedenberg⁷ ;   ; ¹⁵ ; Adolfo Garnica⁸ ; Theresa  ; A. Grebe⁹ ; Dolores Herná ; ndez-Almaguer⁵ ; LaDonna Immken¹⁰ ; Seema  ; R. Lalani¹ ;   ; ² ;   ; ⁴ ; Scott  ; D. McLean¹¹ ; Hope Northrup¹² ; Fernando Scaglia¹ ;   ; ⁴ ; Lane Strathearn² ;   ; ³ ;   ; ⁴ ; Pamela Trapane¹³ ; Sung-Hae  ; L. Kang¹ ; Ankita Patel¹ ; Sau  ; Wai Cheung¹ ; P.J. Hastings¹ ; Paweł ; Stankiewicz¹ ; James  ; R. Lupski¹ ;   ; ² ;   ; ⁴ ;   ; ^{jlupski@bcm.edu} ; Weimin Bi¹
• 刊名：Cell
• 出版年：2011
• 出版时间：16 September 2011
• 年：2011
• 卷：146
• 期：6
• 页码：889-903
• 全文大小：3180 K

文摘

Summary

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.