title: Absence of large intragenic rearrangements in the DPYD gene in a large cohort of colorectal cancer patients treated with 5-FU-based chemotherapy.
abstract: 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.
authors.affiliation: Departments of Genetics, de la Santa Creu i Sant Pau, Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Paré
authors.forename: David
authors.initials: D
authors.lastname: Paez
authors.forename: Juliana
authors.initials: J
authors.lastname: Salazar
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Del Rio
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tizzano
authors.forename: Eugenio
authors.initials: E
authors.lastname: Marcuello
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D004252:DNA Mutational Analysis; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil