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. McLean & 11 others Hope 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 journalArticle

241 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)889-903
Number of pages15
JournalCell
Volume146
Issue number6
DOIs
StatePublished - Sep 16 2011
Externally publishedYes

Fingerprint

Chromosomes
Metabolism
Life cycle
Comparative Genomic Hybridization
Life Cycle Stages
DNA
Neoplasms
Chromothripsis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Liu, P., Erez, A., Nagamani, S. C. S., Dhar, S. U., Kołodziejska, K. E., Dharmadhikari, A. V., ... Bi, W. (2011). Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements. Cell, 146(6), 889-903. https://doi.org/10.1016/j.cell.2011.07.042

Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements. / Liu, Pengfei; Erez, Ayelet; Nagamani, Sandesh C.Sreenath; Dhar, Shweta U.; Kołodziejska, 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, Paweł; Lupski, James R.; Bi, Weimin.

In: Cell, Vol. 146, No. 6, 16.09.2011, p. 889-903.

Research output: Contribution to journalArticle

Liu, P, Erez, A, Nagamani, SCS, Dhar, SU, Kołodziejska, KE, Dharmadhikari, AV, Cooper, ML, Wiszniewska, J, Zhang, F, Withers, MA, Bacino, CA, Campos-Acevedo, LD, Delgado, MR, Freedenberg, D, Garnica, A, Grebe, TA, Hernández-Almaguer, D, Immken, L, Lalani, SR, McLean, SD, Northrup, H, Scaglia, F, Strathearn, L, Trapane, P, Kang, SHL, Patel, A, Cheung, SW, Hastings, PJ, Stankiewicz, P, Lupski, JR & Bi, W 2011, 'Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements', Cell, vol. 146, no. 6, pp. 889-903. https://doi.org/10.1016/j.cell.2011.07.042
Liu P, Erez A, Nagamani SCS, Dhar SU, Kołodziejska KE, Dharmadhikari AV et al. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements. Cell. 2011 Sep 16;146(6):889-903. https://doi.org/10.1016/j.cell.2011.07.042
Liu, Pengfei ; Erez, Ayelet ; Nagamani, Sandesh C.Sreenath ; Dhar, Shweta U. ; Kołodziejska, 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, Paweł ; Lupski, James R. ; Bi, Weimin. / Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements. In: Cell. 2011 ; Vol. 146, No. 6. pp. 889-903.
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