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

Abstract

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.

• Authors: Ryouichi Tsunedomi, Shoichi Hazama, Naoko Okayama, Masaaki Oka, Hiroaki Nagano
• Journal: Cancer science (Cancer Sci) Vol. 108 Issue 7 Pg. 1504-1509 (Jul 2017) ISSN: 1349-7006 [Electronic] England
• PMID: 28474802 (Publication Type: Journal Article)
• Copyright: © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Antineoplastic Agents, Phytogenic
• Irinotecan
• UGT1A1 enzyme
• Glucuronosyltransferase
• Camptothecin

Topics

• Antineoplastic Agents, Phytogenic (adverse effects)
• Camptothecin (adverse effects, analogs & derivatives)
• Colorectal Neoplasms (drug therapy, genetics)
• Genetic Predisposition to Disease (genetics)
• Genetic Testing (methods)
• Genotype
• Glucuronosyltransferase (genetics)
• Humans
• Irinotecan
• Oligonucleotide Array Sequence Analysis (methods)
• Polymorphism, Single Nucleotide