Comprehensive analysis of IDH mutation in intrahepatic cholangio carcinoma

• Project/Area Number: 15K09043
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: Kogure Hirofumi 東京大学, 医学部附属病院, 助教 (60568921)
• Co-Investigator(Kenkyū-buntansha): 立石 敬介 東京大学, 医学部附属病院, 講師 (20396948) ; 濱田 毅 東京大学, 医学部附属病院, 特任臨床医 (90723461)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 胆道癌 / 胆管癌 / 肝内胆管癌 / エピジェネテイクス

Outline of Final Research Achievements

Intrahepatic cholangiocarcinoma (ICC) is a type of bile duct cancers. The mutations of Isocitrate dehydrogenase (IDH) 1 or 2 gene were identified. IDH is a metabolic enzyme converting isocitrate to alpha-ketoglutarate. The mutations in the catalytic sites of them produce a specific metabolite 2-hydroxyglutarate (2-HG) from alpha-ketoglutarate. We aimed to address how IDH mutation affects the feature of biliary cells. We transduced the lentiviral vectors expressing human wild-type IDH1 or mutant IDH1 (R132C) into the mouse biliary cells. In the transduced biliary cells, the global levels of histone modification were altered by IDH mutation. In addition, we found that IDH mutation affect the sensitivy of ICC cells to certain anti-cancer drugs.

Research Products

• [Journal Article] CA19-9 kinetics during systemic chemotherapy in patients with advanced or recurrent biliary tract cancer. (2017)
  • Author(s): Takahara N, Nakai Y, Isayama H, Sasaki T, Saito K, Noguchi K, Suzuki T, Nakamura T, Sato T, Ishigaki K, Hakuta R, Takeda T, Uchino R, Mizuno S, Kogure H, Tada M, Koike K.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 80(6) Issue: 6 Pages: 1105-1112
  • DOI: 10.1007/s00280-017-3456-9
  • Peer Reviewed
• [Journal Article] Gemcitabine and S-1 versus gemcitabine and cisplatin treatment in patients with advanced biliary tract cancer: a multicenter retrospective study. (2017)
  • Author(s): Takahara N, Isayama H, Nakai Y, Sasaki T, Ishigaki K, Saito K, Akiyama D, Uchino R, Mizuno S, Yagioka H, Kogure H, Togawa O, Matsubara S, Ito Y, Toda N, Tada M, Koike K.
  • Journal Title: Invest New Drugs Volume: 35(3) Issue: 3 Pages: 269-276
  • DOI: 10.1007/s10637-017-0430-7
  • Peer Reviewed