Biomarkers associated with malignant transformation in grade II and III gliomas

• Project/Area Number: 25861268
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Nagoya University
• Principal Investigator: MOTOMURA Kazuya 名古屋大学, 医学(系)研究科(研究院), 特任准教授 (30467295)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: グリオーマ / 悪性転化 / 低悪性度神経膠腫 / DMBT1 / MET / IDH1/IDH2変異 / TP53変異 / 1p/19q co-deletion

Outline of Final Research Achievements

Grade II and III gliomas are slowly progressing brain cancers, many of which eventually transform into more aggressive tumors.　Grade II and III gliomas comprise three distinct subtypes characterized by discrete sets of mutations and distinct clinical behaviors. Mutations showed significant positive and negative correlations and a chronological hierarchy, as inferred from different allelic burdens among coexisting mutations, suggesting that there is functional interplay between the mutations that drive clonal selection.

Research Products

• [Journal Article] Mutational landscape and clonal architecture in grade II and III gliomas (2015)
  • Author(s): Suzuki H, Aoki K, Natsume A, Ogawa S. et al.
  • Journal Title: Nat Genet. Volume: 47 Issue: 5 Pages: 458-468
  • DOI: 10.1038/ng.3273
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association of dorsal inferior frontooccipital fasciculus fibers in the deep parietal lobe with both reading and writing processes: a brain mapping study (2014)
  • Author(s): Motomura K, Fujii M, Maesawa S, Kuramitsu S, Natsume A, Wakabayashi T
  • Journal Title: Journal of Neurosurgery Volume: 121(1) Issue: 1 Pages: 142-8
  • DOI: 10.3171/2014.2.jns131234
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Assessment of tumor cells in a mouse model of diffuse infiltrative glioma by Raman spectroscopy. (2014)
  • Author(s): Tanahashi K, Natsume A, Ohka F, Momota H, Kato A, Motomura K, Watabe N, Muraishi S, Nakahara H, Saito Y, Takeuchi I, Wakabayashi T.
  • Journal Title: Biomed Res Int. Volume: 2014 Pages: 860241-860241
  • DOI: 10.1155/2014/860241
  • Peer Reviewed / Open Access
• [Journal Article] Quantitative metabolome analysis profiles activation of glutaminolysis in glioma with IDH1 mutation (2014)
  • Author(s): Ohka, F., Ito, M., Ranjit, M., Senga, T., Motomura, A., Motomura, K., Saito, K., Kato, K., Kato, Y., Wakabayashi, T., Soga, T., Natsume, A.
  • Journal Title: Tumor Biol. Volume: 35 Issue: 6 Pages: 5911-5920
  • DOI: 10.1007/s13277-014-1784-5
  • Peer Reviewed / Open Access
• [Journal Article] Preclinical evaluation of an O6-methylguanine-DNA methyltransferase -siRNA/liposome complex administered by convection-enhanced delivery to rat and porcine brains (2014)
  • Author(s): Tsujiuchi T, Natsume A, Motomura K, Kondo G, Melissa Ranjit, Hachisu R, Sugimura I, Tomita S, Takehara I, Max Woolley, Neil Barua, Steven Gill, Alison Bienemann, Yamashita Y, Toyokuni S, Wakabayashi T
  • Journal Title: Am J Transl Res Volume: 485(1) Pages: 65-70
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma (2014)
  • Author(s): Ando H, Natsume A, Senga T, Watanabe R, Ito I, Ohno M, Iwami K, Ohka F, Motomura K, Kinjo S, Ito M, Saito K, Morgan R, Wakabayashi T
  • Journal Title: Cancer Chemother Pharmacol. Volume: 73(1) Issue: 1 Pages: 53-60
  • DOI: 10.1007/s00280-013-2316-5
  • Peer Reviewed
• [Journal Article] Preclinical evaluation of an O6-methylguanine-DNA methyltransferase -siRNA/liposome complex administered by convection-enhanced delivery to rat and porcine brains (2014)
  • Author(s): Tsujiuchi T, Natsume A, Motomura K, Kondo G, Melissa Ranjit, Hachisu R, Sugimura I, Tomita S, Takehara I, Max Woolley, Neil Barua, Steven Gill, Alison Bienemann, Yamashita Y, Toyokuni S, Wakabayashi T
  • Journal Title: American Journal of Translational Research Volume: 6(2) Pages: 169-178
  • Peer Reviewed
• [Journal Article] Quantitative metabolome analysis profiles activation of glutaminolysis in glioma with IDH1 mutation. (2014)
  • Author(s): Ohka F, Ito M, Ranjit M, Senga T, Motomura A, Motomura K, Saito K, Kato K, Kato Y, Wakabayashi T, Soga T, Natsume A.
  • Journal Title: Tumour Biol Volume: -
  • Peer Reviewed
• [Journal Article] Association of dorsal inferior frontooccipital fasciculus fibers in the deep parietal lobe with both reading and writing processes: a brain mapping study. (2014)
  • Author(s): Motomura K, Fujii M, Maesawa S, Kuramitsu S, Natsume A, Wakabayashi T.
  • Journal Title: J Neurosurg. Volume: -
  • Peer Reviewed
• [Journal Article] MET gain in diffuse astrocytomas is associated with poorer outcome. (2013)
  • Author(s): Pierscianek D, Kim YH, Motomura K, Mittelbronn M, Paulus W, Brokinkel B, Keyvani K, Wrede K, Nakazato Y,Tanaka Y,Mariani L, Vital A, Sure U, Ohgaki H.
  • Journal Title: Brain Pathology Volume: 23(1) Issue: 1 Pages: 13-18
  • DOI: 10.1111/j.1750-3639.2012.00609.x
  • Peer Reviewed
• [Journal Article] PDGFRA Gain in Low-Grade Diffuse Gliomas (2013)
  • Author(s): Motomura K, Mittelbronn M, Paulus W, Brokinkel B, Keyvani K, Sure U, Wrede K, Nakazato Y,Tanaka Y, Nonoguchi N, Pierscianek D, Kim YH, Mariani L, Vital A, Perry A, Ohgaki H
  • Journal Title: J Neuropathol Exp Neurol. Volume: 72(1) Issue: 1 Pages: 61-66
  • DOI: 10.1097/nen.0b013e31827c4b5b
  • Peer Reviewed
• [Journal Article] Lack of presence of the human cytomegalovirus in human glioblastoma. (2013)
  • Author(s): Yamashita Y, Ito Y, Isomura H, Takemura N, Okamoto A, Motomura K, Tsujiuchi T, Natsume A, Wakabayashi T, Toyokuni S, Tsurumi T
  • Journal Title: Mod Pathol Volume: Dec 13 Issue: 7 Pages: 922-9
  • DOI: 10.1038/modpathol.2013.219
  • Peer Reviewed
• [Presentation] Lower grade gliomaの悪性転化に関わる遺伝子解析 (2015)
  • Author(s): 本村和也、鈴木啓道、青木恒介、 夏目敦至、Hiroko Ohgaki、若林俊彦
  • Organizer: 第4回Neuro-Oncology West
  • Place of Presentation: 大阪府大阪市（帝国ホテル大阪）
  • Year and Date: 2015-10-03
  • Invited
• [Presentation] Long-term survival in patients with primary intracranial germ cell tumors treated with surgery, carboplatin based chemotherapy followed by radiotherapy (2014)
  • Author(s): Kazuya Motomura, Atsushi Natsume, Toshihiko Wakabayashi
  • Organizer: 15th European Congress of Neurosurgery (EANS 2014)
  • Place of Presentation: Prague, Czech Republic (Prague Convention Center)
  • Year and Date: 2014-10-15
• [Presentation] グリオーマ治療における覚醒下手術 intraoperative MRIを駆使した外科的摘出術の意義 (2014)
  • Author(s): 本村和也 藤井正純 前澤聡 山本高士 夏目敦至 若林俊彦
  • Organizer: 日本脳神経外科学会第73回学術総会
  • Place of Presentation: 東京都港区（グランドプリンスホテル新高輪 ）
  • Year and Date: 2014-10-09
• [Presentation] 覚醒下手術、intraoperative MRIを 統合させたgrade II/IIIグリオーマに 対する手術戦略 (2014)
  • Author(s): 本村和也 藤井正純 前澤聡 山本高士 夏目敦至 若林俊彦
  • Organizer: 第19回日本脳腫瘍の外科学会
  • Place of Presentation: 東京都文京区（東京ドームホテル）
  • Year and Date: 2014-09-12
• [Presentation] 覚醒下機能マッピングによる、書字・音読に関わる白質線維・dorsal inferior frontooccipital fasciculus (IFOF) の同定 (2014)
  • Author(s): 本村和也 藤井正純 前澤聡 倉光俊一郎 夏目敦至 若林俊彦
  • Organizer: 第12回日本Awake Surgery研究会
  • Place of Presentation: 東京都千代田区（砂防会館）
  • Year and Date: 2014-09-11
• [Presentation] 成人膠芽腫治療ガイドライン～ギリアデル使用の位置づけと当院の使用経験～ (2014)
  • Author(s): 本村和也
  • Organizer: Gliadel Meet the Expert
  • Place of Presentation: 名古屋（名鉄ニューグランドホテル）
  • Year and Date: 2014-08-01
  • Invited
• [Presentation] Intra-tumoral heterogeneity of PDGFRA / MET gain in WHO grade II diffuse astrocytomas (2013)
  • Author(s): Motomura K, Mittelbronn M, Paulus W, Brokinkel B, Keyvani K, Sure U, Wrede K, Nakazato Y,Tanaka Y, Nonoguchi N, Pierscianek D, Kim YH, Mariani L, Vital A, Perry A, Ohgaki H
  • Organizer: AACR Annual Meeting 2013
  • Place of Presentation: Washington, DC, USA
• [Presentation] 脳腫瘍手術における術中運動神経モニタリング
  • Author(s): 本村和也
  • Organizer: 第3回奈良術中神経モニター講習会
  • Place of Presentation: AP大阪駅前梅田1丁目、大阪市
  • Invited
• [Presentation] WHO grade II diffuse astrocytomaに おけるPDGFRA / MET gainの腫瘍内不均一性
  • Author(s): 本村和也、夏目敦至、若林俊彦、Hiroko Ohgaki
  • Organizer: 第31回日本脳腫瘍病理学会
  • Place of Presentation: KFC Hall 国際ファッションセンター、東京都墨田区
• [Book] 神経モニタリングポケットマニュアル 運動誘発電位（皮質下刺激） 運動野近傍脳腫瘍摘出術 (2014)
  • Author(s): 本村 和也
  • Total Pages: 350
  • Publisher: 羊土社
• [Book] 神経症候群Ⅲ-その他の神経疾患を含めて-脳梁部・視床部・視床下部・基底核部の腫瘍（脳室腫瘍を除く） (2014)
  • Author(s): 本村和也、夏目敦至、若林俊彦
  • Total Pages: 883
  • Publisher: 日本臨床