Scrambling the genome in cancer: causes and consequences of complex chromosome rearrangements

Ksenia Krupina; Alexander Goginashvili; Don W Cleveland

doi:10.1038/s41576-023-00663-0

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Scrambling the genome in cancer: causes and consequences of complex chromosome rearrangements

Journal article

Peer reviewed

Scrambling the genome in cancer: causes and consequences of complex chromosome rearrangements

Ksenia Krupina, Alexander Goginashvili and Don W Cleveland

Nature reviews. Genetics, Vol.25(3), pp.196-210

03/01/2024

DOI: 10.1038/s41576-023-00663-0

PMID: 37938738

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Abstract

Complex chromosome rearrangements, known as chromoanagenesis, are widespread in cancer. Based on large-scale DNA sequencing of human tumours, the most frequent type of complex chromosome rearrangement is chromothripsis, a massive, localized and clustered rearrangement of one (or a few) chromosomes seemingly acquired in a single event. Chromothripsis can be initiated by mitotic errors that produce a micronucleus encapsulating a single chromosome or chromosomal fragment. Rupture of the unstable micronuclear envelope exposes its chromatin to cytosolic nucleases and induces chromothriptic shattering. Found in up to half of tumours included in pan-cancer genomic analyses, chromothriptic rearrangements can contribute to tumorigenesis through inactivation of tumour suppressor genes, activation of proto-oncogenes, or gene amplification through the production of self-propagating extrachromosomal circular DNAs encoding oncogenes or genes conferring anticancer drug resistance. Here, we discuss what has been learned about the mechanisms that enable these complex genomic rearrangements and their consequences in cancer.

Cell Nucleus

Chromatin

Chromosome Aberrations

Chromothripsis

DNA - genetics

Gene Rearrangement

Humans

Neoplasms - genetics

Details

Title: Subtitle: Scrambling the genome in cancer: causes and consequences of complex chromosome rearrangements
Creators: Ksenia Krupina - University of California San Diego
Alexander Goginashvili - University of California San Diego
Don W Cleveland - University of California San Diego
Resource Type: Journal article
Publication Details: Nature reviews. Genetics, Vol.25(3), pp.196-210
DOI: 10.1038/s41576-023-00663-0
PMID: 37938738
NLM abbreviation: Nat Rev Genet
ISSN: 1471-0056
eISSN: 1471-0064
Grant note: R35 GM122476 / NIGMS NIH HHS
Language: English
Date published: 03/01/2024
Academic Unit: Biochemistry and Molecular Biology
Record Identifier: 9985134037602771

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