학술논문
DPYD Exome, mRNA Expression and Uracil Levels in Early Severe Toxicity to Fluoropyrimidines: An Extreme Phenotype Approach
Document Type
article
Author
Priscila Villalvazo; Belén Marzal-Alfaro; Pilar García-Alfonso; José Luis Revuelta-Herrero; Fabienne Thomas; Sara López-Tarruella; Xandra García-González; Aitana Calvo; Malika Yakoubi; Sara Salvador-Martín; Flora López-López; Iker Aguilar; María Sanjurjo-Sáez; Miguel Martín; Luis Andrés López-Fernández
Source
Journal of Personalized Medicine, Vol 11, Iss 8, p 792 (2021)
Subject
Language
English
ISSN
2075-4426
Abstract
Dihydropyrimidine dehydrogenase deficiency is a major cause of severe fluoropyrimidine-induced toxicity and could lead to interruption of chemotherapy or life-threatening adverse reactions. This study aimed to characterize the DPYD exon sequence, mRNA expression and in vivo DPD activity by plasma uracil concentration. It was carried out in two groups of patients with extreme phenotypes (toxicity versus control) newly treated with a fluoropyrimidine, during the first three cycles of treatment. A novel nonsense gene variant (c.2197insA) was most likely responsible for fluoropyrimidine-induced toxicity in one patient, while neither DPYD mRNA expression nor plasma uracil concentration was globally associated with early toxicity. Our present work may help improve pharmacogenetic testing to avoid severe and undesirable adverse reactions to fluoropyrimidine treatment and it also supports the idea of looking beyond DPYD.