Mutation rates and fitness consequences of mosaic chromosomal alterations in blood.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
26
08
2022
accepted:
28
07
2023
medline:
6
11
2023
pubmed:
12
9
2023
entrez:
11
9
2023
Statut:
ppublish
Résumé
Mosaic chromosomal alterations (mCAs) are common in cancers and can arise decades before diagnosis. A quantitative understanding of the rate at which these events occur, and their functional consequences, could improve cancer risk prediction and our understanding of somatic evolution. Using mCA clone size estimates from the blood of approximately 500,000 UK Biobank participants, we estimate mutation rates and fitness consequences of acquired gain, loss and copy-neutral loss of heterozygosity events. Most mCAs have moderate to high fitness effects but occur at a low rate, being more than tenfold less common than equivalently fit single-nucleotide variants. Notable exceptions are mosaic loss of X and Y, which we estimate have roughly 1,000-fold higher mutation rates than autosomal mCAs. Although the way in which most mCAs increase in prevalence with age is consistent with constant growth rates, some mCAs exhibit different behavior, suggesting that their fitness may depend on inherited variants, extrinsic factors or distributions of fitness effects.
Identifiants
pubmed: 37697102
doi: 10.1038/s41588-023-01490-z
pii: 10.1038/s41588-023-01490-z
pmc: PMC10562253
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1677-1685Informations de copyright
© 2023. The Author(s).
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