Source:http://linkedlifedata.com/resource/pubmed/id/20010457
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2010-1-28
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pubmed:abstractText |
Gemcitabine (2',2'-difluorodeoxycytidine) is a major antimetabolite cytotoxic drug with a wide spectrum of activity against solid tumors. Hepatic elimination of gemcitabine depends on a catabolic pathway through a deamination step driven by the enzyme cytidine deaminase (CDA). Severe hematologic toxicity to gemcitabine was reported in patients harboring genetic polymorphisms in CDA gene. High-resolution melting (HRM) analysis of polymerase chain reaction amplicon emerges today as a powerful technique for both genotyping and gene scanning strategies. In this study, 46 DNA samples from gemcitabine-treated patients were subjected to HRM analysis on a LightCycler 480 platform. Residual serum CDA activity was assayed as a surrogate marker for the overall functionality of this enzyme. Genotyping of three well-described single nucleotide polymorphisms in coding region (c.79A>C, c.208G>A and c.435C>T) was successfully achieved by HRM analysis of small polymerase chain reaction fragments, whereas unknown single nucleotide polymorphisms were searched by a gene scanning strategy with longer amplicons (up to 622 bp). The gene scanning strategy allowed us to find a new intronic mutation c.246+37G>A in a female patient displaying marked CDA deficiency and who had an extreme toxic reaction with a fatal outcome to gemcitabine treatment. Our work demonstrates that HRM-based methods, owing to their simplicity, reliability, and speed, are useful tools for diagnosis of CDA deficiency and could be of interest for personalized medicine.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1536-3694
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pubmed:author |
pubmed-author:BoyerJean-ChristopheJC,
pubmed-author:BrouilletJean-PaulJP,
pubmed-author:CiccoliniJosephJ,
pubmed-author:EvrardAlexandreA,
pubmed-author:LallemantBenjaminB,
pubmed-author:LumbrosoSergeS,
pubmed-author:MercierCédricC,
pubmed-author:MouzatKévinK,
pubmed-author:PolgeAnneA,
pubmed-author:RaynalCarolineC
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pubmed:issnType |
Electronic
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
53-60
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pubmed:meshHeading |
pubmed-meshheading:20010457-Aged,
pubmed-meshheading:20010457-Antimetabolites, Antineoplastic,
pubmed-meshheading:20010457-Base Sequence,
pubmed-meshheading:20010457-Cytidine Deaminase,
pubmed-meshheading:20010457-Deoxycytidine,
pubmed-meshheading:20010457-Female,
pubmed-meshheading:20010457-Genetic Variation,
pubmed-meshheading:20010457-Genotype,
pubmed-meshheading:20010457-Humans,
pubmed-meshheading:20010457-Male,
pubmed-meshheading:20010457-Mutation,
pubmed-meshheading:20010457-Neoplasms,
pubmed-meshheading:20010457-Polymerase Chain Reaction,
pubmed-meshheading:20010457-Polymorphism, Single Nucleotide,
pubmed-meshheading:20010457-Reproducibility of Results,
pubmed-meshheading:20010457-Transition Temperature
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pubmed:year |
2010
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pubmed:articleTitle |
High-resolution melting analysis of sequence variations in the cytidine deaminase gene (CDA) in patients with cancer treated with gemcitabine.
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pubmed:affiliation |
Laboratoire de Biochimie, Centre Hospitalier Universitaire de Nîmes, Nîmes, France.
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pubmed:publicationType |
Journal Article
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