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Review

Chromothripsis and DNA Repair Disorders

1
Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
2
Center for Genomic Medicine, Rigshospitalet, 2100 Copenhagen, Denmark
3
Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark
4
Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(3), 613; https://doi.org/10.3390/jcm9030613
Received: 28 January 2020 / Revised: 15 February 2020 / Accepted: 19 February 2020 / Published: 25 February 2020
(This article belongs to the Special Issue Clinical Research on Primary Immunodeficiency Diseases)
Chromothripsis is a mutational mechanism leading to complex and relatively clustered chromosomal rearrangements, resulting in diverse phenotypic outcomes depending on the involved genomic landscapes. It may occur both in the germ and the somatic cells, resulting in congenital and developmental disorders and cancer, respectively. Asymptomatic individuals may be carriers of chromotriptic rearrangements and experience recurrent reproductive failures when two or more chromosomes are involved. Several mechanisms are postulated to underlie chromothripsis. The most attractive hypothesis involves chromosome pulverization in micronuclei, followed by the incorrect reassembly of fragments through DNA repair to explain the clustered nature of the observed complex rearrangements. Moreover, exogenous or endogenous DNA damage induction and dicentric bridge formation may be involved. Chromosome instability is commonly observed in the cells of patients with DNA repair disorders, such as ataxia telangiectasia, Nijmegen breakage syndrome, and Bloom syndrome. In addition, germline variations of TP53 have been associated with chromothripsis in sonic hedgehog medulloblastoma and acute myeloid leukemia. In the present review, we focus on the underlying mechanisms of chromothripsis and the involvement of defective DNA repair genes, resulting in chromosome instability and chromothripsis-like rearrangements. View Full-Text
Keywords: chromothripsis; structural variants; DNA repair; DNA repair disorders; DNA double-strand breaks (DSBs); ataxia telangiectasia mutated (ATM); ataxia telangiectasia and Rad3-related (ATR); TP53; micronuclei; chromosome pulverization chromothripsis; structural variants; DNA repair; DNA repair disorders; DNA double-strand breaks (DSBs); ataxia telangiectasia mutated (ATM); ataxia telangiectasia and Rad3-related (ATR); TP53; micronuclei; chromosome pulverization
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MDPI and ACS Style

Nazaryan-Petersen, L.; Bjerregaard, V.A.; Nielsen, F.C.; Tommerup, N.; Tümer, Z. Chromothripsis and DNA Repair Disorders. J. Clin. Med. 2020, 9, 613. https://doi.org/10.3390/jcm9030613

AMA Style

Nazaryan-Petersen L, Bjerregaard VA, Nielsen FC, Tommerup N, Tümer Z. Chromothripsis and DNA Repair Disorders. Journal of Clinical Medicine. 2020; 9(3):613. https://doi.org/10.3390/jcm9030613

Chicago/Turabian Style

Nazaryan-Petersen, Lusine, Victoria A. Bjerregaard, Finn C. Nielsen, Niels Tommerup, and Zeynep Tümer. 2020. "Chromothripsis and DNA Repair Disorders" Journal of Clinical Medicine 9, no. 3: 613. https://doi.org/10.3390/jcm9030613

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