@article {1589996,
	title = {Chromothripsis as an on-target consequence of CRISPR-Cas9 genome editing},
	journal = {Nat Genet},
	volume = {53},
	number = {6},
	year = {2021},
	month = {2021 06},
	pages = {895-905},
	abstract = {Genome editing has therapeutic potential for treating genetic diseases and cancer. However, the currently most practicable approaches rely on the generation of DNA double-strand breaks (DSBs), which can give rise to a poorly characterized spectrum of chromosome structural abnormalities. Here, using model cells and single-cell whole-genome sequencing, as well as by editing at a clinically relevant locus in clinically relevant cells, we show that CRISPR-Cas9 editing generates structural defects of the nucleus, micronuclei and chromosome bridges, which initiate a mutational process called chromothripsis. Chromothripsis is extensive chromosome rearrangement restricted to one or a few chromosomes that can cause human congenital disease and cancer. These results demonstrate that chromothripsis is a previously unappreciated on-target consequence of CRISPR-Cas9-generated DSBs. As genome editing is implemented in the clinic, the potential for extensive chromosomal rearrangements should be considered and monitored.},
	keywords = {Anemia, Sickle Cell, Antigens, CD34, Cell Division, Chromosomes, Human, Chromothripsis, CRISPR-Associated Protein 9, CRISPR-Cas Systems, DNA Cleavage, Gene Editing, Genome, Human, Humans, Micronucleus, Germline, Tumor Suppressor Protein p53},
	issn = {1546-1718},
	doi = {10.1038/s41588-021-00838-7},
	author = {Leibowitz, Mitchell L and Papathanasiou, Stamatis and Doerfler, Phillip A and Blaine, Logan J and Sun, Lili and Yao, Yu and Zhang, Cheng-Zhong and Weiss, Mitchell J and Pellman, David}
}
