Genome-wide epigenetic analysis of glioma and glioma stem-like cells

• Project/Area Number: 26462177
• 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: SAITO KUNIAKI 杏林大学, 医学部, 助教 (50446564)
• Research Collaborator: AIHARA KOKI ; OTANI RYOHEI ; YANAGISAWA SHUNSUKE ; OMATA MAYU
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 神経膠腫 / エピジェネティクス / メチル化 / 幹細胞 / 悪性転化 / IGFBP2

Outline of Final Research Achievements

Methylation markers for glioma malignant progression identified by genome-wide methylation analysis were validated using MassARRAY. The result was highly correlated with Infinium methylation analysis. Many glioma samples, glioma cell line, and glioma stem cells were validated for the methylation markers. Methylation profile of glioma stem cells were similar to that of G-CIMP demethylated group, suggesting malignant progression with demethylation was related to glioma stemness. Demethylation sites in malignantly progressed samples were poorly enriched in Histon methylation marks such as H3K4me3 and H3K27me3 in embryonal stem cells.

Research Products

• [Journal Article] Genetic and epigenetic stability of oligodendrogliomas at recurrence. (2017)
  • Author(s): Aihara K, Mukasa A, Nagae G, Nomura M, Yamamoto S, Ueda H, Tatsuno K, Shibahara J, Takahashi M, Momose T, Tanaka S, Takayanagi S, Yanagisawa S, Nejo T, Takahashi S, Omata M, Otani R, Saito K, Narita Y, Nagane M, Nishikawa R, Ueki K, Aburatani H, Saito N
  • Journal Title: Acta Neuropathol Commun. Volume: 5 Issue: 1 Pages: 18-18
  • DOI: 10.1186/s40478-017-0422-z
  • Peer Reviewed / Open Access
• [Presentation] Upfront chemotherapy prolongs progression free survival of the patients with low-grade oligodendroglial tumors (2016)
  • Author(s): Kuniaki Saito, Keiichi Kobayashi, 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
• [Presentation] Genome-wide methylation analysis identifies genomic DNA demethylaition during malignant progression of gliomas (2014)
  • Author(s): Kuniaki Saito, Akitake Mukasa, Genta Nagae, Koki Aihara, Mayu Omata, Ryohei Otani, Shunsaku Takayangi, Shota Tanaka, Junji Shibahara, Miwako Takahashi, Toshimitsu Momose, Teppei Shimamura, Yoshitaka Narita, Keisuke Ueki, Ryo Nishikawa, Motoo Nagane, Satoru Miyano, Hiroyuki Aburatani and Nobuhito Saito
  • Organizer: 19th Annual Scientific Meeting of the Society for Neuro-Oncology
  • Place of Presentation: Miami Beach, Florida, USA
  • Year and Date: 2014-11-13 – 2014-11-16
• [Presentation] メチル化網羅的解析により同定された神経膠腫悪性転化に伴う脱メチル化 (2014)
  • Author(s): 齊藤 邦昭、武笠 晃丈、永江 玄太、相原 功輝、大谷 亮平、高柳 俊作、小俣 麻友、田中 將太、柴原 純二、成田 善孝、西川 亮、植木 敬介、永根 基雄、油谷 浩幸、齊藤 延人
  • Organizer: 日本脳神経外科学会 第73回学術総会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-09 – 2014-10-11