Tsunedomi Ryouichi, Hazama Shoichi, Okayama Naoko, Oka Masaaki, Nagano Hiroaki
Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University Faculty of Medicine, Ube, Japan.
Cancer Sci. 2017 Jul;108(7):1504-1509. doi: 10.1111/cas.13272. Epub 2017 Jun 5.
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 UGT1A128 and UGT1A16 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 (UGT1A16) and a TA-repeat polymorphism (UGT1A128), 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.
人类基因组学领域的最新进展极大地提升了精准医学和个性化医疗的潜力。我们开发了一种新型DNA微阵列，它采用涂有类金刚石碳的3平方毫米芯片来提高信号背景比，用作精准医学中的体外诊断工具。为了验证这种新开发的DNA微阵列的基因分型有效性，我们检测了转移性结直肠癌患者提取的DNA中的尿苷二磷酸葡萄糖醛酸基转移酶1A1（UGT1A1）多态性。已确定UGT1A128和UGT1A16的多态性与抗癌药物伊立替康诱导的严重毒性显著相关。对于每个样本，将使用新型微阵列平台获得的结果与使用其他更成熟方法（包括直接测序和入侵检测法）获得的结果进行比较。所检测的多态性包括一个单核苷酸取代（UGT1A16）和一个TA重复多态性（UGT1A128），使用我们的方法能够同时且准确地检测到这两种多态性。此外，与入侵检测法相比，我们的方法检测所需时间减少了1.5倍，样本量减少了20倍。总之，我们新开发的DNA微阵列比现有方法更实用，且至少具有相同的准确性；这将提高诊断和治疗开始前多态性检测的效率，并可切实应用于精准医学。
