Elucidation of temporo-spatial heterogeneity of glioma by Liquid Biopsy

• Project/Area Number: 15K15529
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Kyushu University
• Principal Investigator: MIZOGUCHI Masahiro 九州大学, 医学研究院, 共同研究員 (50380621)
• Co-Investigator(Kenkyū-buntansha): 佐山 徹郎 九州大学, 医学研究院, 講師 (30346788) ; 吉本 幸司 九州大学, 大学病院, 講師 (70444784) ; 天野 敏之 九州大学, 医学研究院, 共同研究員 (70448413) ; 橋口 公章 九州大学, 大学病院, 講師 (80448422)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: glioma / liquid biopsy / cell free DNA / microRNA / digital PCR / グリオーマ / 脳腫瘍

Outline of Final Research Achievements

We started Liquid Biopsy by circulating cell free DNA (cfDNA) and microRNA (miRNA) analysis in body fluids for glioma cases. Firstly, global expression analysis of blood miRNA revealed that expression of many miRNA is elevated in glioma cases, and some specific miRNAs could be analyzed also in cerebrospinal fluid. Secondly, cfDNA analysis was undertaken. First, mutation analysis of IDH1 was carried out using the TaqMan method, but due to the small amount of cfDNA, it was difficult to accurately evaluate the mutation, and most of the cases were not analyzable. Next, we introduced digital PCR, and it was clarified that mutation analysis of IDH1 gene is possible by analysis of cfDNA in cerebrospinal fluid.

Research Products

• [Journal Article] Prevalence and clinicopathological features of H3.3 G34-mutant high-grade gliomas: a retrospective study of 411 consecutive glioma cases in a single institution. (2017)
  • Author(s): Yoshimoto K, Hatae R, Sangatsuda Y, Suzuki SO, Hata N, Akagi Y, Kuga D, Hideki M, Yamashita K, Togao O, Hiwatashi A, Iwaki T, Mizoguchi M, Iihara K.
  • Journal Title: Brain Tumor Pathol. Volume: 印刷中 Issue: 3 Pages: 103-112
  • DOI: 10.1007/s10014-017-0287-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A comprehensive analysis identifies BRAF hotspot mutations associated with gliomas with peculiar epithelial morphology. (2016)
  • Author(s): Hatae R, Hata N, Suzuki SO, Yoshimoto K, Kuga D, Murata H, Akagi Y, Sangatsuda Y, Iwaki T, Mizoguchi M, Iihara K.
  • Journal Title: Neuropathology Volume: 28 Issue: 3 Pages: 191-199
  • DOI: 10.1111/neup.12347
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Deferred radiotherapy and upfront procarbazine-ACNU-vincristine administration for 1p19q codeleted oligodendroglial tumors are associated with favorable outcome without compromising patient performance, regardless of WHO grade. (2016)
  • Author(s): Hata N, Yoshimoto K, Hatae R, Kuga D, Akagi Y, Suzuki SO, Iwaki T, Shono T, Mizoguchi M, Iihara K.
  • Journal Title: Onco Targets Ther. Volume: 9 Pages: 7123-7131
  • DOI: 10.2147/ott.s115911
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Insular primary glioblastomas with IDH mutations: Clinical and biological specificities. (2016)
  • Author(s): Hata N, Hatae R, Yoshimoto K, Murata H, Kuga D, Akagi Y, Sangatsuda Y, Suzuki SO, Iwaki T, Mizoguchi M, Iihara K.
  • Journal Title: Neuropathology Volume: 24 Issue: 3 Pages: 200-207
  • DOI: 10.1111/neup.12362
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Add-on bevacizumab can prevent early clinical deterioration and prolong survival in newly diagnosed partially resected glioblastoma patients with a poor performance status. (2016)
  • Author(s): Hata N, Yoshimoto K, Hatae R, Kuga D, Akagi Y, Sangatsuda Y, Suzuki SO, Shono T, Mizoguchi M, Iihara K.
  • Journal Title: Onco Targets Ther. Volume: 10 Pages: 429-437
  • DOI: 10.2147/ott.s125587
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Detection of proneural/mesenchymal marker expression in glioblastoma: temporospatial dynamics and association with chromatin-modifying gene expression (2015)
  • Author(s): Hideki Murata･Koji Yoshimoto･Ryusuke Hatae･Yojiro Akagi･Masahiro Mizoguchi･Nobuhiro Hata･Daisuke Kuga･Akira Nakamizo･Toshiyuki Amano･Tetsuro Sayama･Koji Iihara
  • Journal Title: Journal of Neuro-oncology Volume: 125 Issue: 1 Pages: 33-41
  • DOI: 10.1007/s11060-015-1886-y
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 分子病理学に基づくグリオーマ分類 (2015)
  • Author(s): 溝口昌弘
  • Journal Title: 脳神経外科ジャーナル Volume: 24 Pages: 366-377
  • NAID: 130005083639
  • Peer Reviewed
• [Presentation] グリオーマ400例における1p/19q共欠失の解析 (2016)
  • Author(s): 吉本幸司、溝口昌弘
  • Organizer: 第34回脳腫瘍学会
  • Place of Presentation: 甲府富士屋ホテル
  • Year and Date: 2016-12-04
• [Presentation] 初発神経膠芽腫に対するBevacizumab併用療法の治療成績 (2016)
  • Author(s): 秦暢宏、溝口昌弘
  • Organizer: 第34回脳腫瘍学会
  • Place of Presentation: 甲府富士屋ホテル
  • Year and Date: 2016-12-04
• [Presentation] IDHmutant, 1p19qcodeleted oligodendrogliomaの長期予後に関する検討 (2016)
  • Author(s): 空閑太亮、溝口昌弘
  • Organizer: 第34回脳腫瘍学会
  • Place of Presentation: 甲府富士屋ホテル
  • Year and Date: 2016-12-04
• [Presentation] 1p19q co-deletionを有するolidodendrogliomaに対するPAV療法：分子診断による治療層別化の長期成績 (2016)
  • Author(s): 秦暢宏、溝口昌弘
  • Organizer: 第34回脳腫瘍病理学会
  • Place of Presentation: 東京カンファレンスセンター有明
  • Year and Date: 2016-05-27
• [Presentation] pGBMにおけるIDH/TERT promoter/ch10 LOHの解析 (2015)
  • Author(s): 波多江龍亮、秦暢宏、赤木洋二郎、村田秀樹、空閑太亮、吉本幸司、溝口昌弘、飯原弘二
  • Organizer: 第33回日本脳腫瘍学会学術集会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2015-12-06
• [Presentation] ベバシズマブ時代における悪性神経膠腫の診断と治療 (2015)
  • Author(s): 溝口昌弘
  • Organizer: 日本脳神経外科学会第74回学術総会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2015-10-14
  • Invited
• [Presentation] IDH/TERT変異解析による、グリオーマの分子病理学的層別化：255症例の検討 (2015)
  • Author(s): 波多江龍亮、秦暢宏、赤木洋二郎、村田秀樹、空閑太亮、吉本幸司、溝口昌弘、飯原弘二
  • Organizer: 日本脳神経外科学会第74回学術総会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2015-10-14
• [Presentation] グリオーマ診断における分子病理学の役割 (2015)
  • Author(s): 溝口昌弘、吉本幸司、村田秀樹、波多江龍亮、赤木洋次郎、天野敏之、飯原弘二
  • Organizer: 第33回日本脳腫瘍病理学会
  • Place of Presentation: 香川県高松市
  • Year and Date: 2015-05-29
• [Presentation] 神経膠芽腫症例におけるBRAF遺伝子点突然変異解析 (2015)
  • Author(s): 波多江龍亮、秦暢宏、鈴木諭、赤木洋二郎、村田秀樹、天野敏之、吉本幸司、溝口昌弘、飯原弘二
  • Organizer: 第33回日本脳腫瘍病理学会
  • Place of Presentation: 香川県高松市
  • Year and Date: 2015-05-29