Linked Life Data

14635116

Source:http://linkedlifedata.com/resource/pubmed/id/14635116

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-11-24
pubmed:databankReference
pubmed:abstractText
Complete or partial loss of dihydropyrimidine dehydrogenase (DPD or DYPD) function has been described in cancer patients experiencing severe side effects upon administration of the fluoropyrimidine anticancer drug 5-fluorouracil (5-FU). To investigate a genetic predisposition for 5-FU intolerance due to inherited DPD defects, we established a mutation detection assay based on denaturing HPLC. Analyzing four individuals with symptoms of 5-FU-related toxicity, we detected six distinct sequence variants in the dihydropyrimidine dehydrogenase gene (DPYD): one novel mutation, c.775A>G (K259E); four known missense mutations, c.85T>C (C29R), c.496A>G (M166V), c.1601G>A (S534N), c.1627A>G (I543V); and one silent mutation c.1896T>C affecting the codon for F632. One cancer patient possessing a total of four gene mutations resulting in four amino acid substitutions (C29R, M166V, S534N, I543V) displayed significantly reduced DPD activity. The rare combination of the highly conserved mutation sites M166V and S534N was additionally found in one of the other patients. DPD enzyme activity was low, but yet within normal range. The K259E mutation did not provoke a decrease in DPD function in a heterozygous individual. Based on the protein structure of crystalline pig DPD and the deduced homology models, we have additionally investigated the amino acid positions in their three-dimensional network which correspond to the five missense mutations discovered in the patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1098-1004
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
498
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Detailed analysis of five mutations in dihydropyrimidine dehydrogenase detected in cancer patients with 5-fluorouracil-related side effects.
pubmed:affiliation
Department of Obstetrics & Gynecology, Technical University of Munich, Germany. eva.gross@lrz.tum.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't