Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms
Articolo
Data di Pubblicazione:
2012
Citazione:
Constitutional chromothripsis rearrangements
involve clustered double-stranded DNA breaks
and nonhomologous repair mechanisms / W.P. Kloosterman, M. Tavakoli-Yaraki, M.J. van Roosmalen, E. van Binsbergen, I. Renkens, K. Duran, L. Ballarati, S. Vergult, D. Giardino, K. Hansson, C.A.L. Ruivenkamp, M. Jager, A. van Haeringen, E.F. Ippel, T. Haaf, E. Passarge, R. Hochstenbach, B. Menten, L. Larizza, V. Guryev, M. Poot, E. Cuppen. - In: CELL REPORTS. - ISSN 2211-1247. - 1:6(2012 Jun 28), pp. 648-655.
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
double-stranded DNA breaks (DSBs)
Elenco autori:
W.P. Kloosterman, M. Tavakoli-Yaraki, M.J. van Roosmalen, E. van Binsbergen, I. Renkens, K. Duran, L. Ballarati, S. Vergult, D. Giardino, K. Hansson, C.A.L. Ruivenkamp, M. Jager, A. van Haeringen, E.F. Ippel, T. Haaf, E. Passarge, R. Hochstenbach, B. Menten, L. Larizza, V. Guryev, M. Poot, E. Cuppen
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