Scrambling the genome in cancer: causes and consequences of complex chromosome rearrangements.
Nat Rev Genet
; 25(3): 196-210, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-37938738
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Cromotripsis
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Nat Rev Genet
Asunto de la revista:
GENETICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos