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Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms

(2012) CELL REPORTS. 1(6). p.648-655
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Abstract
Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements.
Keywords
DE-NOVO, BALANCED TRANSLOCATIONS, COMPLEX CHROMOSOMAL REARRANGEMENTS, GERMLINE, MUTATIONS, BREAKPOINTS, GENERATION, RETARDATION, COPY NUMBER, GENOMIC REARRANGEMENTS

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MLA
Kloosterman, Wigard P., et al. “Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms.” CELL REPORTS, vol. 1, no. 6, 2012, pp. 648–55, doi:10.1016/j.celrep.2012.05.009.
APA
Kloosterman, W. P., Tavakoli-Yaraki, M., van Roosmalen, M. J., van Binsbergen, E., Renkens, I., Duran, K., … Cuppen, E. (2012). Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms. CELL REPORTS, 1(6), 648–655. https://doi.org/10.1016/j.celrep.2012.05.009
Chicago author-date
Kloosterman, Wigard P, Masoumeh Tavakoli-Yaraki, Markus J van Roosmalen, Ellen van Binsbergen, Ivo Renkens, Karen Duran, Lucia Ballarati, et al. 2012. “Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms.” CELL REPORTS 1 (6): 648–55. https://doi.org/10.1016/j.celrep.2012.05.009.
Chicago author-date (all authors)
Kloosterman, Wigard P, Masoumeh Tavakoli-Yaraki, Markus J van Roosmalen, Ellen van Binsbergen, Ivo Renkens, Karen Duran, Lucia Ballarati, Sarah Vergult, Daniel Giardino, Kerstin Hansson, Claudia AL Ruivenkamp, Myrthe Jager, Arie van Haeringen, Elly F Ippel, Thomas Haaf, Eberhard Passarge, Ron Hochstenbach, Björn Menten, Lidia Larizza, Victor Guryev, Martin Poot, and Edwin Cuppen. 2012. “Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms.” CELL REPORTS 1 (6): 648–655. doi:10.1016/j.celrep.2012.05.009.
Vancouver
1.
Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, et al. Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms. CELL REPORTS. 2012;1(6):648–55.
IEEE
[1]
W. P. Kloosterman et al., “Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms,” CELL REPORTS, vol. 1, no. 6, pp. 648–655, 2012.
@article{3121952,
  abstract     = {{Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements.}},
  author       = {{Kloosterman, Wigard P and Tavakoli-Yaraki, Masoumeh and van Roosmalen, Markus J and van Binsbergen, Ellen and Renkens, Ivo and Duran, Karen and Ballarati, Lucia and Vergult, Sarah and Giardino, Daniel and Hansson, Kerstin and Ruivenkamp, Claudia AL and Jager, Myrthe and van Haeringen, Arie and Ippel, Elly F and Haaf, Thomas and Passarge, Eberhard and Hochstenbach, Ron and Menten, Björn and Larizza, Lidia and Guryev, Victor and Poot, Martin and Cuppen, Edwin}},
  issn         = {{2211-1247}},
  journal      = {{CELL REPORTS}},
  keywords     = {{DE-NOVO,BALANCED TRANSLOCATIONS,COMPLEX CHROMOSOMAL REARRANGEMENTS,GERMLINE,MUTATIONS,BREAKPOINTS,GENERATION,RETARDATION,COPY NUMBER,GENOMIC REARRANGEMENTS}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{648--655}},
  title        = {{Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms}},
  url          = {{http://doi.org/10.1016/j.celrep.2012.05.009}},
  volume       = {{1}},
  year         = {{2012}},
}

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