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Absence of large intragenic rearrangements in the DPYD gene in a large cohort of colorectal cancer patients treated with 5‐FU‐based chemotherapy
Author(s) -
Paré Laia,
Paez David,
Salazar Juliana,
Del Rio Elisabeth,
Tizzano Eduardo,
Marcuello Eugenio,
Baiget Montserrat
Publication year - 2010
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2010.03683.x
Subject(s) - dpyd , multiplex ligation dependent probe amplification , medicine , colorectal cancer , dihydropyrimidine dehydrogenase , oncology , mutation , genetics , cancer research , chemotherapy , exon , cancer , fluorouracil , biology , genotype , gene , pharmacogenetics , thymidylate synthase
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Dihydropyrimidine dehydrogenase (DPD) is the enzyme responsible for the elimination of approximately 80% of the administered dose of 5‐fluorouracil (5‐FU). • Mutations in the DPD‐coding gene have been shown to increase the risk of severe toxicity in 5‐FU treated patients. • The IVS14+1G>A is the most common DPYD mutation. WHAT THIS STUDY ADDS • The intragenic rearrangements of DPYD using multiplex ligation‐dependent probe amplification (MLPA) were studied for the first time in a large series of 234 colorectal cancer patients treated with 5‐FU‐containing chemotherapy. • No deletions or duplications of one or more DPYD exons were detected. The presence of the IVS14+1G>A mutation was also excluded. • These data show that neither the large genomic rearrangements in the DPYD gene nor the IVS14+1G>A mutation are responsible for the serious toxicity associated with a 5‐FU containing regimen in this cohort of Spanish patients. AIMS To study the relationship between the toxicity associated with a 5‐FU‐based therapy and the presence of (i) the large intragenic rearrangements in the DPYD gene and (ii) the IVS14+1G>A mutation. METHODS We used the multiplex ligation‐dependent probe amplification technique (MLPA) to study genomic DNA from 234 colorectal cancer patients treated with 5‐FU‐based chemotherapy. RESULTS We did not detect any deletion/duplication in the DPYD gene. The presence of the IVS14+1G>A mutation was also excluded. CONCLUSIONS Neither the large genomic rearrangements in the DPYD gene nor the IVS14+1G>A mutation play a significant role in the development of serious toxicity associated with a 5‐FU containing regimen.