2019-10-08
5-Fluorouracil treatment induces characteristic T>G mutations in human cancer
Publication
Publication
Nature Communications , Volume 10 - Issue 1 p. 4571
5-Fluorouracil (5-FU) is a chemotherapeutic drug commonly used for the treatment of solid cancers. It is proposed that 5-FU interferes with nucleotide synthesis and incorporates into DNA, which may have a mutational impact on both surviving tumor and healthy cells. Here, we treat intestinal organoids with 5-FU and find a highly characteristic mutational pattern that is dominated by T>G substitutions in a CTT context. Tumor whole genome sequencing data confirms that this signature is also identified in vivo in colorectal and breast cancer patients who have received 5-FU treatment. Taken together, our results demonstrate that 5-FU is mutagenic and may drive tumor evolution and increase the risk of secondary malignancies. Furthermore, the identified signature shows a strong resemblance to COSMIC signature 17, the hallmark signature of treatment-naive esophageal and gastric tumors, which indicates that distinct endogenous and exogenous triggers can converge onto highly similar mutational signatures.
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| doi.org/10.1038/s41467-019-12594-8, hdl.handle.net/1765/120215 | |
| Nature Communications | |
| Organisation | Department of Medical Oncology |
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Christensen, S. (Sharon), Van der Roest, B. (Bastiaan), Besselink, N., Janssen, R. (Roel), Boymans, S. (Sander), Martens, J., … Van Hoeck, A. (Arne). (2019). 5-Fluorouracil treatment induces characteristic T>G mutations in human cancer. Nature Communications, 10(1). doi:10.1038/s41467-019-12594-8 |
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