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• W2954765035 abstract "Abstract 5-Fluorouracil (5-FU) is a chemotherapeutic drug component that is commonly used for the treatment of solid cancers. It is proposed that 5-FU possesses anticancer properties via the interference with nucleotide synthesis and incorporation into DNA. As both mechanisms may have a mutational impact on both surviving tumor and healthy cells, we treated intestinal organoids with 5-FU followed by whole genome sequencing analysis and uncovered a highly characteristic mutational pattern that is dominated by T>G substitutions in a CTT context. Analysis of tumor whole genome sequencing data confirmed that this signature can also be identified in vivo in colorectal and breast cancer patients that have undergone treatment with 5-FU. We also found that more 5-FU mutations are induced in TP53 null backgrounds which may be of clinical relevance. 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." @default.
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• W2954765035 date "2019-06-25" @default.
• W2954765035 modified "2023-09-27" @default.
• W2954765035 title "5-Fluorouracil treatment induces characteristic T>G mutations in human cancer" @default.
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• W2954765035 doi "https://doi.org/10.1101/681262" @default.
• W2954765035 hasPublicationYear "2019" @default.
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