ArticleGenome biology2016
A comprehensive survey of the mutagenic impact of common cancer cytotoxics.
Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 2 of them syntheses that pooled it.
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Who cites it
107 citing papers in PubMed, 2 syntheses or guidelines pooled it, 187 citations in OpenAlex.
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- Immune-checkpoint inhibitor plus chemotherapy versus conventional chemotherapy for first-line treatment in advanced non-small cell lung carcinoma: a systematic review and meta-analysis.Journal for immunotherapy of cancer · 2018Pooled it
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- Treatment-related mutagenic processes in acute lymphoblastic leukemia.Haematologica · 2025Review
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- Joint inference of mutational signatures from indels and single-nucleotide substitutions reveals prognostic impact of DNA repair deficiencies.Genome medicine · 2025Article
- Melatonin Prevents Cisplatin-Induced Cyto-Histopathological Damage in the Bone Marrow and Inner Ear.International archives of otorhinolaryngology · 2025Article
- DiffInvex identifies evolutionary shifts in driver gene repertoires during tumorigenesis and chemotherapy.Nature communications · 2025Article
- Structural variant and nucleosome occupancy dynamics postchemotherapy in a HER2+ breast cancer organoid model.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting chromosomally unstable tumors with a selective KIF18A inhibitor.Nature communications · 2025Article
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- Rational Approach toward COVID-19's Main Protease Inhibitors: A Hierarchical Biochemoinformatics Analysis.International journal of molecular sciences · 2024Article
- Mutational profile of the regenerative process and de novo genome assembly of the planarian Schmidtea polychroa.Nucleic acids research · 2024Article
- Physiologically-based pharmacokinetic model to predict doxorubicin and paclitaxel exposure in infants through breast milk.CPT: pharmacometrics & systems pharmacology · 2023Article
- DNA mismatch repair protects the genome from oxygen-induced replicative mutagenesis.Nucleic acids research · 2023Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundGenomic mutations caused by cytotoxic agents used in cancer chemotherapy may cause secondary malignancies as well as contribute to the evolution of treatment-resistant tumour cells. The stable diploid genome of the chicken DT40 lymphoblast cell line, an established DNA repair model system, is well suited to accurately assay genomic mutations.
resultsWe use whole genome sequencing of multiple DT40 clones to determine the mutagenic effect of eight common cytotoxics used for the treatment of millions of patients worldwide. We determine the spontaneous mutagenesis rate at 2.3 × 10(-10) per base per cell division and find that cisplatin, cyclophosphamide and etoposide induce extra base substitutions with distinct spectra. After four cycles of exposure, cisplatin induces 0.8 mutations per Mb, equivalent to the median mutational burden in common leukaemias. Cisplatin-induced mutations, including short insertions and deletions, are mainly located at sites of putative intrastrand crosslinks. We find two of the newly defined cisplatin-specific mutation types as causes of the reversion of BRCA2 mutations in emerging cisplatin-resistant tumours or cell clones. Gemcitabine, 5-fluorouracil, hydroxyurea, doxorubicin and paclitaxel have no measurable mutagenic effect. The cisplatin-induced mutation spectrum shows good correlation with cancer mutation signatures attributed to smoking and other sources of guanine-directed base damage.
conclusionThis study provides support for the use of cell line mutagenesis assays to validate or predict the mutagenic effect of environmental and iatrogenic exposures. Our results suggest genetic reversion due to cisplatin-induced mutations as a distinct mechanism for developing resistance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.