Rapid and sensitive detection of UGT1A1 polymorphisms associated with irinotecan toxicity by a novel DNA microarray

Recent developments in the field of human genomics have greatly enhanced the potential for precision and personalized medicine. We have developed a novel DNA microarray, using a 3‐mm square chip coated with diamond‐like carbon to enhance the signal‐to‐background ratio, for use as an in vitro diagnos...

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Veröffentlicht in:Cancer science 2017-07, Vol.108 (7), p.1504-1509
Hauptverfasser: Tsunedomi, Ryouichi, Hazama, Shoichi, Okayama, Naoko, Oka, Masaaki, Nagano, Hiroaki
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container_end_page 1509
container_issue 7
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container_title Cancer science
container_volume 108
creator Tsunedomi, Ryouichi
Hazama, Shoichi
Okayama, Naoko
Oka, Masaaki
Nagano, Hiroaki
description Recent developments in the field of human genomics have greatly enhanced the potential for precision and personalized medicine. We have developed a novel DNA microarray, using a 3‐mm square chip coated with diamond‐like carbon to enhance the signal‐to‐background ratio, for use as an in vitro diagnostic tool in precision medicine. To verify the genotyping effectiveness of this newly developed DNA microarray we examined UDP‐glucuronosyltransferase 1A1 (UGT1A1) polymorphisms in DNA extracted from patients with metastatic colorectal cancer. It is established that the polymorphisms of UGT1A1*28 and UGT1A1*6 are significantly associated with severe toxicity induced by the anti‐cancer drug irinotecan. For each sample, the results obtained with the novel microarray platform were compared with those obtained using other, more established, methods, including direct sequencing and the Invader assay. The polymorphisms tested included a single nucleotide substitution (UGT1A1*6) and a TA‐repeat polymorphism (UGT1A1*28), both of which were detected simultaneously and accurately using our method. Moreover, our method required 1.5‐fold less time to assay and 20‐fold less sample than those required by the Invader assay. In summary, our newly developed DNA microarray is more practical than established methods, and is at least as accurate; this will increase the efficiency of polymorphism detection prior to diagnosis and the commencement of treatment, and can feasibly be applied in precision medicine. A DNA microarray assay for Irinotecan usage. Our newly developed method is feasible and has the potential for wide usage for its rapid and accurate genotyping.
doi_str_mv 10.1111/cas.13272
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subjects Antineoplastic Agents, Phytogenic - adverse effects
Camptothecin - adverse effects
Camptothecin - analogs & derivatives
Colorectal carcinoma
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Deoxyribonucleic acid
DNA
DNA microarray
DNA microarrays
DNA polymerase
Gene expression
Genetic Predisposition to Disease - genetics
Genetic Testing - methods
Genotype
Genotype & phenotype
Genotyping
Glucuronosyltransferase
Glucuronosyltransferase - genetics
Humans
in vitro diagnostics
Irinotecan
Laboratories
Metastases
Metastasis
Methods
Mutation
Oligonucleotide Array Sequence Analysis - methods
Original
Polymorphism
Polymorphism, Single Nucleotide
Precision medicine
Semiconductors
Toxicity
title Rapid and sensitive detection of UGT1A1 polymorphisms associated with irinotecan toxicity by a novel DNA microarray
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