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Trends Cell Biol. 2017 Dec;27(12):917-930. doi: 10.1016/j.tcb.2017.08.005. Epub 2017 Sep 9.

Rebuilding Chromosomes After Catastrophe: Emerging Mechanisms of Chromothripsis.

Author information

1
Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: p3ly@ucsd.edu.
2
Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: dcleveland@ucsd.edu.

Abstract

Cancer genome sequencing has identified chromothripsis, a complex class of structural genomic rearrangements involving the apparent shattering of an individual chromosome into tens to hundreds of fragments. An initial error during mitosis, producing either chromosome mis-segregation into a micronucleus or chromatin bridge interconnecting two daughter cells, can trigger the catastrophic pulverization of the spatially isolated chromosome. The resultant chromosomal fragments are religated in random order by DNA double-strand break repair during the subsequent interphase. Chromothripsis scars the cancer genome with localized DNA rearrangements that frequently generate extensive copy number alterations, oncogenic gene fusion products, and/or tumor suppressor gene inactivation. Here we review emerging mechanisms underlying chromothripsis with a focus on the contribution of cell division errors caused by centromere dysfunction.

KEYWORDS:

DNA repair; chromosome rearrangements; chromothripsis; genomic instability; micronuclei; mitosis

PMID:
28899600
PMCID:
PMC5696049
DOI:
10.1016/j.tcb.2017.08.005
[Indexed for MEDLINE]
Free PMC Article

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