Development of comprehensive platform for molecular diagnosis of glioma

• Project/Area Number: 16K10779
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kyushu University (2017-2018); National Hospital Organization, Kyushu Medical Center (Clinical Institute) (2016)
• Principal Investigator: Hata Nobuhiro 九州大学, 大学病院, 講師 (10596034)
• Co-Investigator(Kenkyū-buntansha): 空閑 太亮 九州大学, 大学病院, 助教 (40759932) ; 吉本 幸司 鹿児島大学, 医歯学域医学系, 教授 (70444784)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: glioma / genetic analysis / molecular diagnosis / WHO2016 / glioblastoma / diffuse glioma / HRM / H3F3A / BRAF / IDH / TERT / H3 K27M / H3 G34R / point mutation / 遺伝子 / 癌 / トランスレーショナルリサーチ / 脳・神経 / ゲノム

Outline of Final Research Achievements

We developed an original genetic analysis method by modifying high resolution melting (HRM) （PLoS One. 2016 Aug 16;11(8):e0160489.）, and established comprehensive platform of HRM, conventional sequencing, LOH and MGMT methylation analyses, that enables systematic molecular diagnosis of glioma in our lab.
Further,we analyzed molecular findings using archival samples and published numerous articles regarding the correlation of molecular diagnoses with clinical characteristics and outcome.

Academic Significance and Societal Importance of the Research Achievements

アーカイブ検体を用いて詳細な遺伝子解析を行い、分子診断と臨床像との関係や治療成績との相関を分析することで、分子診断の意義を報告した。

統合的な解析プラットフォームの構築により、WHO2016分類における分子診断に必須となる遺伝子解析を網羅することが可能となったため、九州大学病院の先進医療：抗悪性腫瘍剤治療における薬剤耐性遺伝子検査、として申請し、2018年8月より稼働している。本先進医療を受けた患者は現在までに約40名に達しており、正確な分子診断に基づいた治療方針を提示することが可能となった。

Research Products

• [Journal Article] An elderly case of malignant small cell glioma with hemorrhage coexistent with a calcified pilocytic astrocytoma component in the cerebellar hemisphere (2018)
  • Author(s): Sangatsuda Yuhei、Hata Nobuhiro、Suzuki Satoshi O.、Akagi Yojiro、Hatae Ryusuke、Kuga Daisuke、Yoshimoto Koji、Momosaki Seiya、Iwaki Toru、Iihara Koji
  • Journal Title: Neuropathology Volume: 38 Issue: 5 Pages: 493-497
  • DOI: 10.1111/neup.12478
  • Peer Reviewed
• [Journal Article] Reclassification of 400 consecutive glioma cases based on the revised 2016WHO classification. (2018)
  • Author(s): Akagi Y, Yoshimoto K, Hata N, Kuga D, Hatae R, Amemiya T, Sangatsuda Y, Suzuki SO, Iwaki T, Mizoguchi M, Iihara K.
  • Journal Title: Brain tumor pathology Volume: 35 Issue: 2 Pages: 81-89
  • DOI: 10.1007/s10014-018-0313-4
  • Peer Reviewed
• [Journal Article] The effectiveness of salvage treatments for recurrent lesions of oligodendrogliomas previously treated with upfront chemotherapy (2018)
  • Author(s): Kuga Daisuke、Hata Nobuhiro、Akagi Yojiro、Amemiya Takeo、Sangatsuda Yuhei、Hatae Ryusuke、Yoshimoto Koji、Mizoguchi Masahiro、Iihara Koji
  • Journal Title: World Neurosurgery Volume: in press Pages: e735-e742
  • DOI: 10.1016/j.wneu.2018.03.069
  • Peer Reviewed
• [Journal Article] Pediatric ganglioglioma with an H3 K27M mutation arising from the cervical spinal cord (2018)
  • Author(s): Okuda Tomohiro、Hata Nobuhiro、Suzuki Satoshi O、Yoshimoto Koji、Arimura Koichi、Amemiya Takeo、Akagi Yojiro、Kuga Daisuke、Oba Utako、Koga Yuhki、Ohga Shouichi、Iwaki Toru、Iihara Koji
  • Journal Title: Neuropathology Volume: in press Issue: 4 Pages: 422-427
  • DOI: 10.1111/neup.12471
  • Peer Reviewed
• [Journal Article] High-resolution melting and immunohistochemical analysis efficiently detects mutually exclusive genetic alterations of adamantinomatous and papillary craniopharyngiomas (2017)
  • Author(s): Yoshimoto Koji、Hatae Ryusuke、Suzuki Satoshi O.、Hata Nobuhiro、Kuga Daisuke、Akagi Yojiro、Amemiya Takeo、Sangatsuda Yuhei、Mukae Nobutaka、Mizoguchi Masahiro、Iwaki Toru、Iihara Koji
  • Journal Title: Neuropathology Volume: 38 Issue: 1 Pages: 3-10
  • DOI: 10.1111/neup.12408
  • Peer Reviewed
• [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] Precise Detection of IDH1/2 and BRAF Hotspot Mutations in Clinical Glioma Tissues by a Differential Calculus Analysis of High-Resolution Melting Data. (2016)
  • Author(s): Hatae R, Hata N, Yoshimoto K, Kuga D, Akagi Y, Murata H, Suzuki SO, Mizoguchi M, Iihara K.
  • Journal Title: PLoS One. Volume: 11 Issue: 8 Pages: e0160489-e0160489
  • DOI: 10.1371/journal.pone.0160489
  • 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
• [Presentation] The correlation between 1p19q and TERT promoter mutation status in IDH-mutant gliomas (2018)
  • Author(s): Nobuhiro Hata, Masahiro MIizoguchi, Yojiro Akagi, Satoshi O Suzuki, Daisuke Kuga, Takeo Amemiya, Ryusuke Hatae, Koji Yoshimoto, Toru Iwaki, Koji Iihara
  • Organizer: The 19th International Congress of Neuropathology
  • Int'l Joint Research
• [Presentation] 改良HRM解析法による、高精度なグリオーマ分子診断法の開発 (2017)
  • Author(s): 秦暢宏、波多江龍亮、吉本幸司、空閑大亮、赤木洋二郎、三月田祐平、鈴木諭、岩城徹、溝口昌弘、飯原弘二
  • Organizer: 日本脳腫瘍病理学会
• [Presentation] 高解像度融解曲線の２階微分解析による、グリオーマ点変異の高精度判定：HRM-MI法 (2017)
  • Author(s): 秦暢宏、波多江龍亮、吉本幸司、空閑大亮、雨宮健生、赤木洋二郎、三月田祐平、溝口昌弘、飯原弘二
  • Organizer: 日本分子脳神経外科学会
• [Presentation] 1p19q co-deletionを有する oligodendrogliomaに対するPAV先行治療：分子診断による治療層別化の長期成績 (2017)
  • Author(s): 秦 暢宏、吉本 幸司、空閑 太亮、波多江龍亮、赤木 洋二郎、鈴木 諭、岩城 徹、 溝口 昌弘、飯原 弘二
  • Organizer: 第34回日本脳腫瘍病理学会
  • Place of Presentation: 東京
• [Presentation] 初発膠芽腫に対するBevacizumab承認後の新規治療戦略：現況と展望 (2016)
  • Author(s): 秦 暢宏、吉本幸司、溝口昌弘、波多江龍亮、赤木洋二郎、三月田祐平、空閑太亮、 庄野禎久、飯原弘二
  • Organizer: 第75回日本脳神経外科学会総会
  • Place of Presentation: 福岡県 福岡市
• [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、吉本幸司、空閑太亮、 波多江龍亮、赤木洋二郎、三月田祐平、溝口昌弘、、飯原弘二
  • Organizer: 第34回日本脳腫瘍学会
  • Place of Presentation: 山梨県 甲府市
• [Presentation] Deferred Radiotherapy and Upfront Procarbazine-ACNU-Vincristine Administration for 1p19q Codeleted Oligodendroglial Tumors is Associated with Favorable Outcome without Compromising Patient Performance, Regardless of WHO Grade (2016)
  • Author(s): Nobuhiro HATA, Koji YOSHIMOTO, Daisuke KUGA, Ryusuke HATAE, Yojiro AKAGI, Satoshi O SUZUKI, Toru IWAKI, Masahiro MIZOGUCHI, Koji IIHARA
  • Organizer: The 14th Young-Honam and Kyushu Neurosurgical Joint Meeting
  • Place of Presentation: 福岡県 福岡市
  • Int'l Joint Research