• Cancer Chemother. Pharmacol. · Aug 2009

    Lack of large intragenic rearrangements in dihydropyrimidine dehydrogenase (DPYD) gene in fluoropyrimidine-treated patients with high-grade toxicity.

    • Ivana Ticha, Petra Kleiblova, Julie Fidlerova, Jan Novotny, Petr Pohlreich, and Zdenek Kleibl.
    • Institute of Biochemistry and Experimental Oncology, 1st Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic.
    • Cancer Chemother. Pharmacol. 2009 Aug 1; 64 (3): 615-8.

    PurposeDeficiency of dihydropyrimidine dehydrogenase (DPD) has been associated with severe fluoropyrimidines (FP) toxicity. Mutations in DPD-coding gene (DPYD) were shown to increase the risk of severe toxicity in FP-treated cancer patients. However, the majority of DPYD alterations characterized in these patients has been considered as polymorphisms and known deleterious mutations are rare and present in only limited subgroup of patients with high toxicity. Recently, the common fragile site FRA1E was mapped within DPYD locus but intragenic rearrangements in DPYD gene were not studied so far.MethodsWe performed the analysis of intragenic rearrangements of DPYD using multiplex ligation-dependent probe amplification in 68 patients with high-grade gastrointestinal and/or hematological toxicity developed at the beginning of FP treatment.ResultsWe did not detect any deletion/duplication of one or more DPYD exons in analyzed patients.ConclusionsWe assume that rearrangements in DPYD gene play insignificant role in the development of serious FP-related toxicity.

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