Chromothripsis – Extensive Chromosomal Rearrangements and Their Significance in Cancer

Authors: K. Závacká 1;  K. Plevová 1,2;  M. Jarošová 1;  Š. Pospíšilová 1,2
Authors‘ workplace: Centrum molekulární bio logie a genové terapie, Interní hematologická a onkologická klinika LF MU a FN Brno 1;  Centrum molekulární medicíny, CEITEC – Středoevropský technologický institut, Masarykova univerzita, Brno 2
Published in: Klin Onkol 2019; 32(2): 101-108
Category: Review
doi: 10.14735/amko2019101



Chromosome rearrangements play an important role in cancer pathophysiology. Recently, chromothripsis has been proposed among the mechanisms leading to their formation. Chromothripsis leads to fragmentation of chromosomes and their reconstitution with tens to hundreds of rearrangements clustered in small genome regions. In contrast to the traditional concept of malignant transformation, abnormalities caused by chromothripsis are not accumulated gradually but arise during a single event. The resulting structural variants are extensive and often cause oncogene activation or tumor suppressor inactivation. Chromothripsis is associated with many tumor types, especially with brain and bone tumors. Besides that, it has been described also in congenital disorders. The exact mechanism of chromothripsis origin has not been clarified yet; however, several hypotheses have been prosed, among which DNA damage in micronucleus seems to be most likely. Similarly, an impact of chromothripsis on cellular processes has not been fully understood, yet its association with unfavorable prognosis has been observed.


The purpose of this article is to summarize the current knowledge about chromothripsis and to present gathered pieces of information in a structured way. We focused on describing the basic features of chromothripsis, potential mechanisms of its origin, its impact on cellular processes and providing an overview of diseases where chromothripsis has been noted, with particular attention to cancer. Finally, we suggest a potential use of current knowledge about chromothripsis in the optimization of personalized treatment.

Supported by Ministry of Health of the Czech Republic, grant no. 15-31834A. All rights reserved.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted: 31. 12. 2018

Accepted: 19. 3. 2019


chromothripsis – Chromosomes – DNA – Mutation – genomic structural variation – DNA end-joining repair


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