Mutation accumulation in mtDNA of cancers resembles mutagenesis in normal stem cells.
Cancer
Genomics
Stem cells research
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
22 Dec 2022
22 Dec 2022
Historique:
received:
02
06
2022
revised:
26
10
2022
accepted:
14
11
2022
entrez:
2
12
2022
pubmed:
3
12
2022
medline:
3
12
2022
Statut:
epublish
Résumé
Mitochondria are small organelles that play an essential role in the energy production of eukaryotic cells. Defects in their genomes are associated with diseases, such as aging and cancer. Here, we analyzed the mitochondrial genomes of 532 whole-genome sequencing samples from cancers and normal clonally expanded single cells. We show that the mitochondria of normal cells accumulate mutations with age and that most of the mitochondrial mutations found in cancer are the result of healthy mutation accumulation. We also show that the normal HSPCs of patients with leukemia have an increased mitochondrial mutation load. Finally, we show that secondary pediatric cancers and chemotherapy treatments do not impact the mitochondrial mutation load and mtDNA copy numbers of most cells, suggesting that damage to the mitochondrial genome is not a major driver for carcinogenesis. Overall, these findings may contribute to our understanding of mitochondrial genomes and their role in cancer.
Identifiants
pubmed: 36458259
doi: 10.1016/j.isci.2022.105610
pii: S2589-0042(22)01882-X
pmc: PMC9707047
doi:
Types de publication
Journal Article
Langues
eng
Pagination
105610Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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