Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-10-20
pubmed:abstractText
Polymorphisms in the thymidylate synthase enhancer region (TSER) have been reported to be associated with alterations in thymidylate synthase (TS) mRNA protein levels. The TSER is characterized by the presence of variable double (2R) and triple (3R) number tandem repeats (VNTRs). In addition to VNTRs, single nucleotide polymorphisms (SNPs) and allelic imbalance (AI), including loss of heterozygosity (LOH), have recently been associated with response to 5-fluorouracil (5-FU)-based chemotherapy. The aim of the current study was to develop a specific denaturing high-performance liquid chromatography (DHPLC) method for the rapid detection of these variations in the TSER in clinical samples. DHPLC analysis was validated in parallel with agarose gel electrophoresis (AGE), enzyme digestion, and quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR). The optimized DHPLC method resolved 100% of the known TSER variations, differentiated between homozygous and heterozygous genotypes, and allowed the qualitative and quantitative detection of AI, including LOH, in tumor samples. This DHPLC method was developed to permit the rapid, sensitive, and accurate identification of the TSER genotype (VNTRs, SNPs, and AI) in clinical protocols where response to flouropyrimidines may be correlated with TSER polymorphisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0003-2697
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
334
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
276-83
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15494134-Allelic Imbalance, pubmed-meshheading:15494134-Cell Line, Tumor, pubmed-meshheading:15494134-Chromatography, High Pressure Liquid, pubmed-meshheading:15494134-DNA, pubmed-meshheading:15494134-Deoxyribonucleases, Type II Site-Specific, pubmed-meshheading:15494134-Electrophoresis, Agar Gel, pubmed-meshheading:15494134-Enhancer Elements, Genetic, pubmed-meshheading:15494134-Gene Frequency, pubmed-meshheading:15494134-Heterozygote, pubmed-meshheading:15494134-Homozygote, pubmed-meshheading:15494134-Humans, pubmed-meshheading:15494134-Nucleic Acid Denaturation, pubmed-meshheading:15494134-Polymorphism, Single Nucleotide, pubmed-meshheading:15494134-RNA, Messenger, pubmed-meshheading:15494134-Sensitivity and Specificity, pubmed-meshheading:15494134-Tandem Repeat Sequences, pubmed-meshheading:15494134-Thymidylate Synthase
pubmed:year
2004
pubmed:articleTitle
Simultaneous detection of variable number tandem repeats, single nucleotide polymorphisms, and allelic imbalance in the thymidylate synthase gene enhancer region using denaturing high-performance liquid chromatography.
pubmed:affiliation
Department of Clinical Pharmacology, University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, AL 35294, USA.
pubmed:publicationType
Journal Article