Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis.
APOBEC deaminases
cancer cell lines
episodic mutagenesis
mutational signatures
xenografts
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
07 03 2019
07 03 2019
Historique:
received:
05
10
2017
revised:
19
09
2018
accepted:
27
01
2019
entrez:
9
3
2019
pubmed:
9
3
2019
medline:
7
1
2020
Statut:
ppublish
Résumé
Multiple signatures of somatic mutations have been identified in cancer genomes. Exome sequences of 1,001 human cancer cell lines and 577 xenografts revealed most common mutational signatures, indicating past activity of the underlying processes, usually in appropriate cancer types. To investigate ongoing patterns of mutational-signature generation, cell lines were cultured for extended periods and subsequently DNA sequenced. Signatures of discontinued exposures, including tobacco smoke and ultraviolet light, were not generated in vitro. Signatures of normal and defective DNA repair and replication continued to be generated at roughly stable mutation rates. Signatures of APOBEC cytidine deaminase DNA-editing exhibited substantial fluctuations in mutation rate over time with episodic bursts of mutations. The initiating factors for the bursts are unclear, although retrotransposon mobilization may contribute. The examined cell lines constitute a resource of live experimental models of mutational processes, which potentially retain patterns of activity and regulation operative in primary human cancers.
Identifiants
pubmed: 30849372
pii: S0092-8674(19)30161-8
doi: 10.1016/j.cell.2019.02.012
pmc: PMC6424819
pii:
doi:
Substances chimiques
Retroelements
0
DNA
9007-49-2
APOBEC Deaminases
EC 3.5.4.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1282-1294.e20Subventions
Organisme : Cancer Research UK
ID : C98/A24032
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 098051
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206194
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.
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