Novel methylation markers of glioma and glioma stemcell and their application to individualized medicine

• Project/Area Number: 15K10342
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kyorin University
• Principal Investigator: Kobayashi Keiichi 杏林大学, 医学部, 学内講師 (70406990)
• Co-Investigator(Renkei-kenkyūsha): NAGANE Motoo 杏林大学, 医学部, 教授 (60327468) ; SAITO Kuniaki 杏林大学, 医学部, 助教 (50446564)
• Research Collaborator: SHIMIZU Saki 杏林大学, 医学部, 実験助手
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経膠腫 / メチル化 / パイロシークエンス / MGMT / IGFBP2 / 幹細胞 / パイロシーケンス

Outline of Final Research Achievements

We performed methylation analysis of glioma and glioma stemcell using pyrosequencing to find novel methylation marker. Methylation of MGMT, known prognostic factor, and IGFBP2 were analyzed. IGFBP2 methylation revealed to predict glioma grade. Furthermore, methylation level of IGFBP2 was significantly lower in glioma stemcell, indicating that IGFBP2 was associated with stemness and could be therapeutic target of glioma.

Research Products

• [Presentation] Prognostic significance of MGMT promoter and mismatch repair system in newly-diagnosed and recurrent malignant gliomas (2017)
  • Author(s): Kuniaki Saito, Saki Shimizu, Kaori Suzuki, Keiichi Kobayashi, Yoshiaki Shiokawa, Motoo Nagane
  • Organizer: 5th Quadrennial Meeting of the World Federation of Neuro-Oncology Societies (WFNOS)
  • Int'l Joint Research
• [Presentation] Integrated molecular analysis of newly diagnosed and recurrent glioblastoma after temozolomide treatment (2017)
  • Author(s): Kuniaki Saito, Kaori Suzuki, Saki Shimizu, Keiichi Kobayashi, Daisuke Shimada, Zentaro Kawaida, Tomohiro Chiba, Junji Shibahara, Yoshiaki Shiokawa, Motoo Nagane
  • Organizer: 第35回日本脳腫瘍病理学会
• [Presentation] Goal-setting of extent of resection on the basis of molecular status in glioma surgery (2017)
  • Author(s): Kuniaki Saito, Kaori Suzuki, Saki Shimizu, Keiichi Kobayashi, Daisuke Shimada, Zentaro Kawaida, Kazuhiro Chiba, Junji Shibahara, Yoshiaki Shiokawa, Motoo Nagane
  • Organizer: 第76回日本脳神経外科学会学術総会
• [Presentation] Temozolomide-induced mismatch repair insufficiency and hypermethylation of MGMT promoter with hypermutation in malignant glioma (2017)
  • Author(s): Kuniaki Saito, Saki Shimizu, Kaori Suzuki, Keiichi Kobayashi, Daisuke Shimada, Satosi Kume, Shohei Iijima, Tomohiro Chiba, Junji Shibahara, Yoshiaki Shiokawa, Motoo Nagane
  • Organizer: 22nd Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology
  • Int'l Joint Research
• [Presentation] Integrated molecular analysis of newly diagnosed and recurrent glioblastoma after temozolomide treatment (2017)
  • Author(s): Kuniaki Saito, Saki Shimizu, Kaori Suzuki, Keiichi Kobayashi, Daisuke Shimada, Satosi Kume, Shohei Iijima, Tomohiro Chiba, Junji Shibahara, Yoshiaki Shiokawa, Motoo Nagane
  • Organizer: 第35回日本脳腫瘍学会学術集会
• [Presentation] Upfront chemotherapy prolongs progression free survival of the patients with low-grade oligodendroglial tumors (2016)
  • Author(s): Kuniaki Saito, Keiichi Kobayasi, Saki Shimizu, Kaori Suzuki, Yoshiaki Shiokawa, Motoo Nagane
  • Organizer: 21st Annual Scientific Meeting of the Society for Neuro-Oncology
  • Place of Presentation: Scottsdale, Arizona, USA
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] Integrated analysis of MGMT promoter methylation and mismatch repair alteration in glioma (2016)
  • Author(s): Kuniaki Saito, Saki Shimizu, Kaori Suzuki, Keiichi Kobayashi, Yoshiaki Shiokawa, Motoo Nagane
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] Integrated analysis of methylation of MGMT promoter and alteration of mismatch repair enzymes in glioblastoma (2016)
  • Author(s): Motoo Nagane, Kuniaki Saito, Keiichi Kobayashi, Saki Shimizu, Kaori Suzuki, Nobuyoshi Sasaki, Satoshi Kume, Yuki Yamagishi, Yoshiaki Shiokawa
  • Organizer: 13th Asian Society for Neuro-Oncology Meeting
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2016-09-11
  • Int'l Joint Research
• [Presentation] 神経膠腫におけるMGMTメチル化とDNAミスマッチ修復酵素の統合解析 (2015)
  • Author(s): 齊藤邦昭、小林啓一、清水早紀、鈴木香、佐々木重嘉、久米賢、川井田善太郎、塩川芳昭、永根基雄
  • Organizer: 第33会日本脳腫瘍学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2015-12-07
• [Presentation] ミスマッチ修復酵素異常が初発膠芽腫の予後に与える影響 (2015)
  • Author(s): 齊藤邦昭、小林啓一、清水早紀、鈴木香、川井田善太郎、今井大也、塩川芳昭、永根基雄
  • Organizer: 第24回多摩脳腫瘍研究会
  • Place of Presentation: 東京
  • Year and Date: 2015-11-28
• [Presentation] Mismatch Repair defects predict clinical outcome of primary and recurrent malignant gliomas (2015)
  • Author(s): Kuniaki Saito, Saki Shimizu, Kaori Suzuki, Keiichi Kobayashi, Nobuyoshi Sasaki, Satoshi Kume, Yoshiaki Shiokawa, Motoo Nagane
  • Organizer: 20th Annual Scientific Meeting of the Society for Neuro-Oncology
  • Place of Presentation: San Antonio, USA
  • Year and Date: 2015-11-20
  • Int'l Joint Research
• [Presentation] MGMTメチル化とDNAミスマッチ修復酵素の異常に応じた膠芽腫治療の展望 (2015)
  • Author(s): 齊藤邦昭、小林啓一、清水早紀、鈴木香、佐々木重嘉、久米賢、塩川芳昭、永根基雄
  • Organizer: 第74回日本脳神経外科学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2015-10-14
• [Presentation] 低悪性度神経膠腫再発時におけるMGMTメチル化/ミスマッチ修復タンパク発現の変化 (2015)
  • Author(s): 齊藤邦昭、小林啓一、清水早紀、鈴木香、佐々木重嘉、久米賢、塩川芳昭、永根基雄
  • Organizer: 第29回東京脳腫瘍治療懇話会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-19