Whole exome sequencing detects variants of genes that mediate response to anticancer drugs

• Ohnami Sumiko

  Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute

• Nagashima Takeshi

  Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute SRL Inc.

• Urakami Kenichi

  Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute

• Shimoda Yuji

  Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute SRL Inc.

• Kamada Fukumi

  Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute

• Saito Junko

  Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute

• Naruoka Akane

  Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute

• Serizawa Masakuni

  Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute

• Masuda Yoko

  Regional Resources Division, Shizuoka Cancer Center Research Institute

• Ohnami Shumpei

  Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute

• Kusuhara Masatoshi

  Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute Regional Resources Division, Shizuoka Cancer Center Research Institute

• Yamaguchi Ken

  Shizuoka Cancer Center Hospital Shizuoka Cancer Center Research Institute

抄録

Certain interindividual differences affecting the efficacy of drug treatment and adverse drug reactions are caused by genetic variants, and their phenotypic effects differ among ethnic groups. In this study, we used whole exome sequencing (WES) systematically to identify germline mutations that influence the activities of drug-metabolizing enzymes, as well as that of a transporter. We analyzed DNA isolated from blood samples from 2,042 Japanese patients with diverse cancers. We identified sequence variants of CYP2B6 (rs3745274), CYP2C9 (rs1057910), CYP2C19 (rs4986893), CYP2C19 (rs4244285), TPMT (rs1142345), NAT2 (rs1799930), NAT2 (rs1799931), UGT1A1 (rs4148323), COMT (rs4680), ABCB1 (rs1045642), and CDA (rs60369023). Wider application of WES will help to determine the effects of mutations on the activities of proteins encoded by drug response genes, and the information gained will accelerate the development of personalized therapies for patients with cancer. Moreover, this knowledge may provide clues for preventing cancer before the onset of symptoms.

収録刊行物

• Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ

  Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ 42 (2), 137-144, 2017

  一般社団法人　日本毒性学会

キーワード

• Whole exome sequencing
• Drug response genes
• Personalized medicine

詳細情報

• CRID: 1390001204906670848
• NII論文ID: 130005450526
• NII書誌ID: AN00002808
• DOI: 10.2131/jts.42.137
• ISSN: 18803989
• ISSN: 03881350
• NDL書誌ID: 028152702
• PubMed: 28321040
• Web Site: http://id.ndl.go.jp/bib/028152702
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I028152702
• Web Site: https://www.jstage.jst.go.jp/article/jts/42/2/42_137/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2017347195
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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