Abstract 239: Development of DNA chip for detection of predictive SNPs for gemcitabine-induced adverse events

Abstract

Abstract [Introduction] Anticancer agent gemcitabine is one of the effective chemotherapies and has been widely used for the treatment of patients with various tumors. However, 13-35% of patients receiving gemcitabine experience severe leukopenia/neutropenia. In our previous studies, we identified four novel SNPs (rs11141915, rs1901440, rs11719165 and rs12046844) associated with this toxicity. To predict the risk of gemcitabine-induced myelosuppression, we developed a high accuracy DNA chip system for genotyping of these four SNPs. [Methods] We used 17 and 170 germline DNA samples of patients who received gemcitabine therapy in the first stage and second stage respectively. For SNP genotyping using the DNA chip, we amplified target regions by PCR with 10 ng of DNA extracted from blood samples. The PCR product was hybridized with the probe on the DNA chip. Genotype was detected by genotyping score, which was calculated the ratio of risk allele fluorescence intensity to total fluorescence intensity. To confirm the accuracy and reliability of this method, TaqMan genotyping assay was performed for 187 samples. [Results and Discussion] In the first stage, genotypes of 17 samples were clearly divided into 3 types (non-risk type homo, hetero type, risk type homo). We defined an appropriate cut off value of genotyping score for detection of genotype according to the results of first stage. In the second stage, 170 samples, whose genotype were unknown, were genotyped using the DNA chip. The genotype results were completely concordant (100%) with those using TaqMan genotyping assay. Our DNA chip system is extremely useful as a simple method that is capable of genotyping using DNAs extracted from small amount of blood samples in general hospitals. The development of our DNA chip system provides new insights into personalized anti-cancer drug therapy including gemcitabine for the patients with cancer. Citation Format: Noriaki Nakamura, Koichi Hirayama, Hirofumi Yamano, Hiroshi Okamura, Hitoshi Zembutsu. Development of DNA chip for detection of predictive SNPs for gemcitabine-induced adverse events [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 239.