RT Journal Article
T1 DPYD Exome, mRNA Expression and Uracil Levels in Early Severe Toxicity to Fluoropyrimidines: An Extreme Phenotype Approach
A1 Villalvazo, Priscila
A1 Marzal Alfaro, Belén
A1 García Alfonso, María Pilar
A1 Revuelta Herrero, José Luis
A1 Thomas, Fabienne
A1 López Tarruella, Sara
A1 García González, Xandra
A1 Calvo, Aitana
A1 Yakoubi, Malika
A1 Salvador Martín, Sara
A1 López López, Flora
A1 Aguilar, Iker
A1 Sanjurjo Sáez, María
A1 Martín, Miguel
A1 López Fernández, Luis Andrés
AB 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.
PB MPDI
SN 2075-4426
YR 2021
FD 2021-08-13
LK https://hdl.handle.net/20.500.14352/4833
UL https://hdl.handle.net/20.500.14352/4833
LA eng
NO Instituto de Investigación Sanitaria Gregorio Marañón
DS Docta Complutense
RD 9 may 2025