Antiviral treatment causes a unique mutational signature in cancers of transplantation recipients.
antiviral treatment
cancer genomics
cytomegalovirus
ganciclovir
hematopoietic stem cell transplantation
mutational signatures
somatic mutations
therapy-related neoplasms
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
07 10 2021
07 10 2021
Historique:
received:
11
01
2021
revised:
11
06
2021
accepted:
29
07
2021
pubmed:
9
9
2021
medline:
26
10
2021
entrez:
8
9
2021
Statut:
ppublish
Résumé
Genetic instability is a major concern for successful application of stem cells in regenerative medicine. However, the mutational consequences of the most applied stem cell therapy in humans, hematopoietic stem cell transplantation (HSCT), remain unknown. Here we characterized the mutation burden of hematopoietic stem and progenitor cells (HSPCs) of human HSCT recipients and their donors using whole-genome sequencing. We demonstrate that the majority of transplanted HSPCs did not display altered mutation accumulation. However, in some HSCT recipients, we identified multiple HSPCs with an increased mutation burden after transplantation. This increase could be attributed to a unique mutational signature caused by the antiviral drug ganciclovir. Using a machine learning approach, we detected this signature in cancer genomes of individuals who received HSCT or solid organ transplantation earlier in life. Antiviral treatment with nucleoside analogs can cause enhanced mutagenicity in transplant recipients, which may ultimately contribute to therapy-related carcinogenesis.
Identifiants
pubmed: 34496298
pii: S1934-5909(21)00337-4
doi: 10.1016/j.stem.2021.07.012
pmc: PMC8516432
pii:
doi:
Substances chimiques
Antiviral Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1726-1739.e6Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests A.R.H., A.v.L., and R.v.B. are named as inventors on a patent application filed resulting from this work.
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