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

• Published in: Cancer science Vol. 108; no. 7; pp. 1504 - 1509
• Main Authors: Tsunedomi, Ryouichi, Hazama, Shoichi, Okayama, Naoko, Oka, Masaaki, Nagano, Hiroaki
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.07.2017; John Wiley and Sons Inc
• 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; Japan; DNA microarray; in vitro diagnostics; precision medicine; polymorphism; irinotecan
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13272

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.