Detection of a Novel 1905C→T Mutation within the Dihydropyrimidine Dehydrogenase Gene and Potential for Misclassification with the Exon 14-skipping Mutation

[摘要] Dihydropyrimidine dehydrogenase (DPYD) is the initial and rate-limiting enzyme in the metabolism of the chemotherapeutic drug 5-fluorouracil (5-FU), thus affecting its pharmacokinetics, efficacy, and toxicity (1). Application of 5-FU is restricted by a narrow therapeutic index because of severe toxicity of WHO grades III–IV (2). Polymorphisms within the DPYD gene have been reported, with deficiency in enzyme activity leading to severe 5-FU-related toxicity in cancer patients (3). The so-called exon 14-skipping mutation at the 5′-splice donor site of exon 14 (1905 + 1G→A) has been detected in ∼25% of affected patients (4). To identify patients at increased risk for severe 5-FU-induced toxicity, many medical centers routinely screen for the exon 14-skipping mutation before starting chemotherapy.We directly compared DNA sequencing with …

[学科分类] 过敏症与临床免疫学