Investigating the prognostic factors of IDH wild-type glioma based on the comprehensive genomic analysis

• Project/Area Number: 17K10862
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Nagoya University
• Principal Investigator: MOTOMURA KAZUYA 名古屋大学, 医学系研究科, 准教授 (30467295)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 低悪性度神経膠腫 / IDH1 / 悪性転化 / グリオーマ / IDH野生型神経膠腫 / 包括的ゲノムプロファイリング

Outline of Final Research Achievements

The clinical significance of genetic lesions within each lower-grade gliomas (LGG) subtype has not been fully elucidated. In this study, they identified sets of subtype-specific genetic and clinicopathological markers for each WHO subtype. The study subjects were a large cohort of patients who were genotyped for known or putative driver mutations and copy number variations associated with LGGs. Importantly, given that LGGs frequently have an indolent clinical history, the subjects were followed up for sufficiently long periods to accurately evaluate overall survival.

Academic Significance and Societal Importance of the Research Achievements

低悪性度神経膠腫におけるDMBT1及びMET遺伝子の機能について、他に同様の報告はされていない。本研究において、DMBT1及びMET 遺伝子とgrade IIIグリオーマ細胞株の相互作用や悪性転化・増殖に関わる機能解析を行ったことで、腫瘍発生・進展・増殖及び悪性転化に関わるメカニズムの解明につながる。今後、難治性腫瘍である悪性グリオーマに対する新たな治療戦略の一つとして期待され、個別化医療の実現を可能にするバイオマーカーとなる可能性を秘めている。

Research Products

• [Journal Article] 特集 グリオーマ-現在の常識と近未来のスタンダード Ⅴ各種グリオーマの集学的治療戦略 低悪性度グリオーマ (2021)
  • Author(s): 本村 和也
  • Journal Title: Neurological Surgery 脳神経外科 Volume: 49 Issue: 3 Pages: 632-639
  • DOI: 10.11477/mf.1436204437
  • ISSN: 0301-2603, 1882-1251
  • Year and Date: 2021-05-10
• [Journal Article] Intraoperative seizure outcome of levetiracetam combined with perampanel therapy in patients with glioma undergoing awake brain surgery (2021)
  • Author(s): Motomura Kazuya、Chalise Lushun、Shimizu Hiroyuki、Yamaguchi Junya、Nishikawa Tomohide、Ohka Fumiharu、Aoki Kosuke、Tanahashi Kuniaki、Hirano Masaki、Wakabayashi Toshihiko、Natsume Atsushi
  • Journal Title: Journal of Neurosurgery Volume: 135 Issue: 4 Pages: 998-1007
  • DOI: 10.3171/2020.8.jns201400
  • Peer Reviewed
• [Journal Article] Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury (2021)
  • Author(s): Fukuoka Toshiki、Kato Akira、Hirano Masaki、Ohka Fumiharu、Aoki Kosuke、Awaya Takayuki、Adilijiang Alimu、Sachi Maeda、Tanahashi Kuniaki、Yamaguchi Junya、Motomura Kazuya、Shimizu Hiroyuki、Nagashima Yoshitaka、Ando Ryo、Wakabayashi Toshihiko、Lee-Liu Dasfne、Larrain Juan、Nishimura Yusuke、Natsume Atsushi
  • Journal Title: iScience Volume: 24 Issue: 2 Pages: 102074-102074
  • DOI: 10.1016/j.isci.2021.102074
  • Peer Reviewed / Open Access
• [Journal Article] Effects of insular resection on interactions between cardiac interoception and emotion recognition (2021)
  • Author(s): Terasawa Yuri、Motomura Kazuya、Natsume Atsushi、Iijima Kentaro、Chalise Lushun、Sugiura Junko、Yamamoto Hiroyasu、Koyama Kyohei、Wakabayashi Toshihiko、Umeda Satoshi
  • Journal Title: Cortex Volume: 137 Pages: 271-281
  • DOI: 10.1016/j.cortex.2021.01.011
  • Peer Reviewed / Open Access
• [Journal Article] Urinary MicroRNA-Based Diagnostic Model for Central Nervous System Tumors Using Nanowire Scaffolds (2021)
  • Author(s): Kitano Yotaro、Aoki Kosuke、Ohka Fumiharu、Yamazaki Shintaro、Motomura Kazuya、Tanahashi Kuniaki、Hirano Masaki、Naganawa Tsuyoshi、Iida Mikiko、Shiraki Yukihiro、Nishikawa Tomohide、Shimizu Hiroyuki、Yamaguchi Junya、Maeda Sachi、Suzuki Hidenori、Wakabayashi Toshihiko、Baba Yoshinobu、Yasui Takao、Natsume Atsushi
  • Journal Title: ACS Applied Materials & Interfaces Volume: 13 Issue: 15 Pages: 17316-17329
  • DOI: 10.1021/acsami.1c01754
  • Peer Reviewed / Open Access
• [Journal Article] Impact of the extent of resection on the survival of patients with grade II and III gliomas using awake brain mapping (2021)
  • Author(s): Motomura Kazuya、Chalise Lushun、Ohka Fumiharu、Aoki Kosuke、Tanahashi Kuniaki、Hirano Masaki、Nishikawa Tomohide、Yamaguchi Junya、Shimizu Hiroyuki、Wakabayashi Toshihiko、Saito Ryuta
  • Journal Title: Journal of Neuro-Oncology Volume: - Issue: 2 Pages: 361-372
  • DOI: 10.1007/s11060-021-03776-w
  • NAID: 120007180217
  • Peer Reviewed
• [Journal Article] Mathematical Modeling and Mutational Analysis Reveal Optimal Therapy to Prevent Malignant Transformation in Grade II IDH-Mutant Gliomas (2021)
  • Author(s): Aoki Kosuke、Suzuki Hiromichi、Yamamoto Takashi、Yamamoto Kimiyo N.、Maeda Sachi、Okuno Yusuke、Ranjit Melissa、Motomura Kazuya、et al
  • Journal Title: Cancer Research Volume: 81 Issue: 18 Pages: 4861-4873
  • DOI: 10.1158/0008-5472.can-21-0985
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Newly established patient-derived organoid model of intracranial meningioma (2021)
  • Author(s): Yamazaki Shintaro、Ohka Fumiharu、Hirano Masaki、Shiraki Yukihiro、Motomura Kazuya et al
  • Journal Title: Neuro-Oncology Volume: 23 Issue: 11 Pages: 1936-1948
  • DOI: 10.1093/neuonc/noab155
  • Peer Reviewed / Open Access
• [Journal Article] Survival Benefit of Supratotal Resection in a Long-term Survivor of <i>IDH</i>-wildtype Glioblastoma: A Case Report and Literature Review (2021)
  • Author(s): YAMAGUCHI Junya、MOTOMURA Kazuya、OHKA Fumiharu、AOKI Kosuke、TANAHASHI Kuniaki、HIRANO Masaki、CHALISE Lushun、NISHIKAWA Tomohide、SHIMIZU Hiroyuki、NATSUME Atsushi、WAKABAYASHI Toshihiko、SAITO Ryuta
  • Journal Title: NMC Case Report Journal Volume: 8 Issue: 1 Pages: 747-753
  • DOI: 10.2176/nmccrj.cr.2021-0120
  • NAID: 130008113034
  • ISSN: 2188-4226
  • Peer Reviewed / Open Access
• [Journal Article] Reliability of IDH1-R132H and ATRX and/or p53 immunohistochemistry for molecular subclassification of Grade 2/3 gliomas (2021)
  • Author(s): Nishikawa Tomohide、Watanabe Reiko、Kitano Yotaro、Yamamichi Akane、Motomura Kazuya、Ohka Fumiharu、Aoki Kosuke、Hirano Masaki、Kato Akira、Yamaguchi Junya、Maeda Sachi、Kibe Yuji、Saito Ryuta、Wakabayashi Toshihiko、Kato Yukinari、Sato Shuta、Ogino Tomoyoshi、Natsume Atsushi、Ito Ichiro
  • Journal Title: Brain Tumor Pathology Volume: 39 Issue: 1 Pages: 14-24
  • DOI: 10.1007/s10014-021-00418-x
  • Peer Reviewed
• [Journal Article] Long-term survival in patients with primary intracranial germ cell tumors treated with surgery, platinum-based chemotherapy, and radiotherapy: a single-institution study (2020)
  • Author(s): Shimizu Hiroyuki、Motomura Kazuya、Ohka Fumiharu、Aoki Kosuke、Tanahashi Kuniaki、Hirano Masaki、Chalise Lushun、Nishikawa Tomohide、Yamaguchi Junya、Yoshida Jun、Natsume Atsushi、Wakabayashi Toshihiko
  • Journal Title: Journal of Neurosurgery Volume: － Issue: 2 Pages: 1-9
  • DOI: 10.3171/2020.6.jns20638
  • Peer Reviewed
• [Journal Article] Multiple metastases to the bone and bone marrow from a 1p/19q-codeleted and IDH2-mutant anaplastic oligodendroglioma: a case report and literature review (2020)
  • Author(s): Shimizu Hiroyuki、Motomura Kazuya、Ohka Fumiharu、Aoki Kosuke、Tanahashi Kuniaki、Hirano Masaki、Chalise Lushun、Nishikawa Tomohide、Yamaguchi Junya、Wakabayashi Toshihiko、Natsume Atsushi
  • Journal Title: Neuro-Oncology Advances Volume: 2 Issue: 1 Pages: 1-9
  • DOI: 10.1093/noajnl/vdaa101
  • Peer Reviewed / Open Access
• [Journal Article] Navigated repetitive transcranial magnetic stimulation as preoperative assessment in patients with brain tumors (2020)
  • Author(s): Motomura Kazuya、Takeuchi Hiroki、Nojima Ippei、Aoki Kosuke、Chalise Lushun、Iijima Kentaro、Wakabayashi Toshihiko、Natsume Atsushi
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 1-1
  • DOI: 10.1038/s41598-020-65944-8
  • Peer Reviewed / Open Access
• [Journal Article] Trautmann-focused mastoidectomy for a simple, safe presigmoid approach: technical note. (2020)
  • Author(s): Tanahashi K, Uda K, Araki Y, Takeuchi K, Choo J, Chalise L, Motomura K, Ohka F, Wakabayashi T, Natsume A.
  • Journal Title: J Neurosurg. Volume: 3 Issue: 3 Pages: 1-5
  • DOI: 10.3171/2020.1.jns193179
  • Peer Reviewed
• [Journal Article] H3F3A mutant allele specific imbalance in an aggressive subtype of diffuse midline glioma, H3 K27M-mutant. (2020)
  • Author(s): Maeda S, Ohka F, Okuno Y, Aoki K, Motomura K, Takeuchi K, Kusakari H, Yanagisawa N, Sato S, Yamaguchi J, Tanahashi K, Hirano M, Kato A, Shimizu H, Kitano Y, Yamazaki S, Yamashita S, Takeshima H, Shinjo K, Kondo Y, Wakabayashi T, Natsume A.
  • Journal Title: Acta Neuropathologica Communications Volume: 8 Issue: 1 Pages: 8-19
  • DOI: 10.1186/s40478-020-0882-4
  • Peer Reviewed / Open Access
• [Journal Article] Preoperative predictive factors affecting return to work in patients with gliomas undergoing awake brain mapping. (2020)
  • Author(s): Yoshida A, Motomura K, Natsume A, Chalise L, Iijima K, Hara D, Kadono I, Wakai K, Wakabayashi T.
  • Journal Title: J Neurooncol. Volume: 146(1) Issue: 1 Pages: 195-205
  • DOI: 10.1007/s11060-019-03371-0
  • Peer Reviewed
• [Journal Article] Next Generation Sequencing-Based Transcriptome Predicts Bevacizumab Efficacy in Combination with Temozolomide in Glioblastoma. (2019)
  • Author(s): Adilijiang A, Hirano M, Okuno Y, Aoki K, Ohka F, Maeda S, Tanahashi K, Motomura K, Shimizu H, Yamaguchi J, Wakabayashi T, Natsume A.
  • Journal Title: Molecules Volume: 24(17) Issue: 17 Pages: 3046-3046
  • DOI: 10.3390/molecules24173046
  • Peer Reviewed / Open Access
• [Journal Article] Spontaneous Tumor Regression of Intracranial Solitary Fibrous Tumor Originating From the Medulla Oblongata: A Case Report and Literature Review. (2019)
  • Author(s): Yamaguchi J, Motomura K, Ohka F, Aoki K, Tanahashi K, Hirano M, Nishikawa T, Shimizu H, Wakabayashi T, Natsume A.
  • Journal Title: World Neurosurg Volume: 130 Pages: 400-404
  • DOI: 10.1016/j.wneu.2019.07.052
  • Peer Reviewed
• [Journal Article] Anterior insular cortex stimulation and its effects on emotion recognition. (2019)
  • Author(s): Motomura K, Terasawa Y, Natsume A, Iijima K, Chalise L, Sugiura J, Yamamoto H, Koyama K, Wakabayashi T, Umeda S.
  • Journal Title: Brain Struct Funct. Volume: 224(6) Issue: 6 Pages: 2167-2181
  • DOI: 10.1007/s00429-019-01895-9
  • Peer Reviewed
• [Journal Article] Neurocognitive and functional outcomes in patients with diffuse frontal lower-grade gliomas undergoing intraoperative awake brain mapping. (2019)
  • Author(s): Motomura K, Chalise L, Ohka F, Aoki K, Tanahashi K, Hirano M, Nishikawa T, Yamaguchi J, Shimizu H, Wakabayashi T, Natsume A.
  • Journal Title: J Neurosurg. Volume: 17 Issue: 6 Pages: 1-9
  • DOI: 10.3171/2019.3.jns19211
  • Peer Reviewed
• [Journal Article] Aberrant Active cis-Regulatory Elements Associated with Downregulation of RET Finger Protein Overcome Chemoresistance in Glioblastoma (2019)
  • Author(s): Ranjit Melissa、Hirano Masaki、Aoki Kosuke、Okuno Yusuke、Ohka Fumiharu、Yamamichi Akane、Kato Akira、Maeda Sachi、Motomura Kazuya、Matsuo Keitaro、Enomoto Atsushi、Ino Yasushi、Todo Tomoki、Takahashi Masahide、Wakabayashi Toshihiko、Kato Takuya、Natsume Atsushi
  • Journal Title: Cell Reports Volume: 26 Issue: 9 Pages: 2274-2281
  • DOI: 10.1016/j.celrep.2019.01.109
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Validation of a novel molecular RPA classification in glioblastoma (GBM-molRPA) treated with chemoradiation: A multi-institutional collaborative study. (2018)
  • Author(s): Wee CW, Kim IH, Park CK, Kim JW, Dho YS, Ohka F, Aoki K, Motomura K, Natsume A, Kim N, Suh CO, Chang JH, Kim SH, Cho WK, Lim DH, Nam DH, Choi JW, Kim IA, Kim CY, Oh YT, Cho O, Chung WK, Kim SH, Kim E.
  • Journal Title: Radiother Oncol. Volume: 129(2) Issue: 2 Pages: 347-351
  • DOI: 10.1016/j.radonc.2018.09.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Immunohistochemical ATRX expression is not a surrogate for 1p19q codeletion (2018)
  • Author(s): Yamamichi Akane、Ohka Fumiharu、Aoki Kosuke、Suzuki Hiromichi、Kato Akira、Hirano Masaki、Motomura Kazuya、Tanahashi Kuniaki、Chalise Lushun、Maeda Sachi、Wakabayashi Toshihiko、Kato Yukinari、Natsume Atsushi
  • Journal Title: Brain Tumor Pathology Volume: - Issue: 2 Pages: 106-113
  • DOI: 10.1007/s10014-018-0312-5
  • NAID: 120006496406
  • Peer Reviewed
• [Journal Article] A novel high-sensitivity assay to detect a small fraction of mutant IDH1 using droplet digital PCR. (2018)
  • Author(s): Hirano M, Ohka F, Maeda S, Chalise L, Yamamichi A, Aoki K, Kato A, Tanahashi K, Motomura K, Nishimura Y, Hara M, Shinjo K, Kondo Y, Wakabayashi T, Natsume A.
  • Journal Title: Brain Tumor Pathol. Volume: 35(2) Pages: 97-105
  • Peer Reviewed
• [Journal Article] Prognostic relevance of genetic alterations in diffuse lower-grade gliomas (2017)
  • Author(s): Aoki Kosuke、Nakamura Hideo、Suzuki Hiromichi et al.
  • Journal Title: Neuro-Oncology Volume: 20 Issue: 1 Pages: 66-77
  • DOI: 10.1093/neuonc/nox132
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A novel all-in-one intraoperative genotyping system for IDH1-mutant glioma. (2017)
  • Author(s): Ohka F, Yamamichi A, Kurimoto M, Motomura K, Tanahashi K, Suzuki H, Aoki K, Deguchi S, Chalise L, Hirano M, Kato A, Nishimura Y, Hara M, Kato Y, Wakabayashi T, Natsume A.
  • Journal Title: Brain Tumor Pathol. Volume: 印刷中 Issue: 2 Pages: 91-97
  • DOI: 10.1007/s10014-017-0281-0
  • NAID: 120006331835
  • Peer Reviewed