Interplay between DNA damage repair and apoptosis shapes cancer evolution through aneuploidy and microsatellite instability.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 03 2020
06 03 2020
Historique:
received:
27
08
2019
accepted:
14
02
2020
entrez:
8
3
2020
pubmed:
8
3
2020
medline:
7
7
2020
Statut:
epublish
Résumé
Driver mutations and chromosomal aneuploidy are major determinants of tumorigenesis that exhibit complex relationships. Here, we identify associations between driver mutations and chromosomal aberrations that define two tumor clusters, with distinct regimes of tumor evolution underpinned by unique sets of mutations in different components of DNA damage response. Gastrointestinal and endometrial tumors comprise a separate cluster for which chromosomal-arm aneuploidy and driver mutations are mutually exclusive. The landscape of driver mutations in these tumors is dominated by mutations in DNA repair genes that are further linked to microsatellite instability. The rest of the cancer types show a positive association between driver mutations and aneuploidy, and a characteristic set of mutations that involves primarily genes for components of the apoptotic machinery. The distinct sets of mutated genes derived here show substantial prognostic power and suggest specific vulnerabilities of different cancers that might have therapeutic potential.
Identifiants
pubmed: 32144251
doi: 10.1038/s41467-020-15094-2
pii: 10.1038/s41467-020-15094-2
pmc: PMC7060240
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1234Références
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