{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:16:58Z","timestamp":1790774218853,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T00:00:00Z","timestamp":1582588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Danish Council for Independent Research (DFF)","award":["4183-00482B"],"award-info":[{"award-number":["4183-00482B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/jcm9030613","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T08:12:22Z","timestamp":1582618342000},"page":"613","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Chromothripsis and DNA Repair Disorders"],"prefix":"10.3390","volume":"9","author":[{"given":"Lusine","family":"Nazaryan-Petersen","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark"},{"name":"Center for Genomic Medicine, Rigshospitalet, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria Alexandra","family":"Bjerregaard","sequence":"additional","affiliation":[{"name":"Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finn Cilius","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Rigshospitalet, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Tommerup","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-5802","authenticated-orcid":false,"given":"Zeynep","family":"T\u00fcmer","sequence":"additional","affiliation":[{"name":"Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cell.2010.11.055","article-title":"Massive genomic rearrangement acquired in a single catastrophic event during cancer development","volume":"144","author":"Stephens","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.cell.2013.02.023","article-title":"Criteria for inference of chromothripsis in cancer genomes","volume":"152","author":"Korbel","year":"2013","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev.biochem.052308.093131","article-title":"The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway","volume":"79","author":"Lieber","year":"2010","journal-title":"Annu. 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