Faculty, Staff and Student Publications

Publication Date

7-1-2025

Journal

Nature Genetics

DOI

10.1038/s41588-025-02234-x

PMID

40596443

PMCID

PMC12283364

PubMedCentral® Posted Date

7-1-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Several chemotherapeutic agents act by increasing DNA damage in cancer cells, triggering cell death. However, there is limited understanding of the extent and long-term consequences of collateral DNA damage in normal tissues. To investigate the impact of chemotherapy on mutation burdens and the cell population structure of normal tissue, we sequenced blood cell genomes from 23 individuals aged 3-80 years who were treated with a range of chemotherapy regimens. Substantial additional somatic mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but the effects were dependent on the drug and blood cell types. Chemotherapy induced premature changes in the cell population structure of normal blood, similar to those caused by normal aging. The results show the long-term biological consequences of cytotoxic agents to which a substantial fraction of the population is exposed as part of disease management, raising mechanistic questions and highlighting opportunities for the mitigation of adverse effects.

Keywords

Humans, Middle Aged, Aged, Adolescent, Child, Adult, Child, Preschool, Aged, 80 and over, Young Adult, Male, Female, Mutation, Blood Cells, Antineoplastic Agents, DNA Damage, Neoplasms, Cancer, Genomics

Comments

This article has been corrected. See Nat Genet. 2025 Jul 31;57(8):2075.

Published Open-Access

yes

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