Lethal outcome of a patient with a complete dihydropyrimidine dehydrogenase (DPD) deficiency after administration of 5-fluorouracil: frequency of the common IVS14+1G>A mutation causing DPD deficiency

A mutation in the invariant GT splice donor site flanking exon 14 (IVS14+1G>A). As a consequence, no significant residual activity of DPD was detected in peripheral blood mononuclear cells. To determine the frequency of the IVS14+1G>A mutation in the Dutch population, we developed a novel PCR-based method allowing the rapid analysis of the IVS14+1G>A mutation by RFLP. Screening for the presence of this mutation in 1357 Caucasians showed an allele frequency of 0.91%. In our view, the apparently high prevalence of the IVS14+1G>A mutation in the normal population, with 1.8% heterozygotes, warrants genetic screening for the presence of this mutation in cancer patients before the administration of 5FU -->
Jazyk: English
ISSN: 1078-0432
Přístupová URL adresa: https://explore.openaire.eu/search/publication?articleId=narcis______::c49fdfae88e1027b445f4d3cf10ba283
https://pure.amc.nl/en/publications/lethal-outcome-of-a-patient-with-a-complete-dihydropyrimidine-dehydrogenase-dpd-deficiency-after-administration-of-5fluorouracil-frequency-of-the-common-ivs141ga-mutation-causing-dpd-deficiency(5de58691-4b54-443f-bc91-31d966c4e5b7).html
Rights: RESTRICTED
Přírůstkové číslo: edsair.narcis........c49fdfae88e1027b445f4d3cf10ba283
Autor: van Kuilenburg, A. B., Muller, E. W., Haasjes, J., Meinsma, R., Zoetekouw, L., Waterham, H. R., Baas, F., Richel, D. J., van Gennip, A. H.
Přispěvatelé: Other departments
Jazyk: angličtina
Rok vydání: 2001
Zdroj: Clinical cancer research, 7(5), 1149-1153. American Association for Cancer Research Inc.
ISSN: 1078-0432
Popis: Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5FU), and it is suggested that patients with a partial deficiency of this enzyme are at risk from developing a severe 5FU-associated toxicity. In this study, we demonstrated that a lethal toxicity after a treatment with 5FU was attributable to a complete deficiency of DPD. Analysis of the DPD gene for the presence of mutations showed that the patient was homozygous for a G-->A mutation in the invariant GT splice donor site flanking exon 14 (IVS14+1G>A). As a consequence, no significant residual activity of DPD was detected in peripheral blood mononuclear cells. To determine the frequency of the IVS14+1G>A mutation in the Dutch population, we developed a novel PCR-based method allowing the rapid analysis of the IVS14+1G>A mutation by RFLP. Screening for the presence of this mutation in 1357 Caucasians showed an allele frequency of 0.91%. In our view, the apparently high prevalence of the IVS14+1G>A mutation in the normal population, with 1.8% heterozygotes, warrants genetic screening for the presence of this mutation in cancer patients before the administration of 5FU
Databáze: OpenAIRE
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