Stratification of hardly classifiable brain tumors by combining detailed pathological and genetic analysis

• Project/Area Number: 19K07411
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Gunma University
• Principal Investigator: Yokoo Hideaki 群馬大学, 大学院医学系研究科, 教授 (40282389)
• Co-Investigator(Kenkyū-buntansha): 信澤 純人 群馬大学, 大学院医学系研究科, 准教授 (80635318) ; 松村 望 群馬大学, 大学院医学系研究科, 講師 (20729511) ; 伊古田 勇人 群馬大学, 医学部附属病院, 准教授 (90420116)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 人体病理学 / 分子病理学 / 神経病理学 / 脳腫瘍 / 悪性グリオーマ

Outline of Research at the Start

適切な診断と正確な予後予測は病理診断に課せられた大きな使命である。しかし、脳腫瘍においては今なお診断困難な症例が少なくない。すべての脳腫瘍の患者さんが最適な治療を受けられるようにするために、病理医の努力の余地はまだ十分に残されている。今回の申請では分類困難あるいは希少な脳腫瘍に光を当てて、膨大な累積脳腫瘍検体から該当例を抽出し、そこに分子遺伝学的プロファイリングを加えて腫瘍概念の輪郭や生物学的特徴を明らかにしていく。

Outline of Final Research Achievements

It is a social requirement of the current era to refine the pathological diagnosis of brain tumors based on molecular genetic findings and to appropriately stratify individual cases, and pathology that is in a position to bridge the basics and clinical practice should play a big role regarding this. The applicants have established a technique for performing genome-wide analysis from a limited size of formalin-fixed paraffin-embedded (FFPE) sections, and have conducted basic research on divergent brain tumors. In this application, we shed light on difficult-to-classify or rare brain tumors, extracted relevant cases from a huge number of cumulative brain tumor samples, and added molecular genetic profiling to clarify the outline and biological characteristics of the tumor concept. On the other hand, at present, there are some cases where proper stratification is difficult, and we proposed the concept of a framework for properly handling such cases.

Academic Significance and Societal Importance of the Research Achievements

広く海外を見渡すと、地域単位、国単位、あるいは国際間で脳腫瘍研究に関する多施設連携プロジェクトが展開されており、申請者はこの研究課題を本邦を代表する脳腫瘍の研究プロジェクトに発展させる責務があると考えて取り組んできた。申請者の所属施設は半世紀にわたり脳腫瘍症例の収集を続けており、研究規模、研究戦略、研究成果は海外勢と比較しても決して引けを取らない水準にある。これをさらに推し進めて、累積希少症例の遺伝子データマイニングと高精細な病理診断を融合させ、我が国を代表する脳腫瘍の研究拠点形成を目指すという当初の目的はある程度達成できたと考える。引き続き発展を目指してまいりたい。

Research Products

• [Journal Article] Subtype-dependent difference of glucose transporter 1 and hexokinase II expression in craniopharyngioma: an immunohistochemical study (2021)
  • Author(s): Mukada Naoto、Tosaka Masahiko、Matsumura Nozomi、Yamaguchi Rei、Aihara Masanori、Isoda Koji、Higuchi Tetsuya、Tsushima Yoshito、Yokoo Hideaki、Yoshimoto Yuhei
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 126-126
  • DOI: 10.1038/s41598-020-80259-4
  • Peer Reviewed / Open Access
• [Journal Article] Ependymoma-like tumor with mesenchymal differentiation harboring C11orf95-NCOA1/2 or -RELA fusion: A hitherto unclassified tumor related to ependymoma (2021)
  • Author(s): Tomomasa R, Arai Y, Kawabata-Iwakawa R, Fukuoka K, Nakano Y, Hama N, Nakata S, Suzuki N, Ishi Y, Tanaka S, Takahashi JA, Yuba Y, Shiota M, Natsume A, Kurimoto M, Shiba Y, Aoki M, Nabeshima K, Enomoto T, Inoue T, Fujimura J, Kondo A, Yao T, Okura N, Hirose T, Sasaki A, Hirato J, Yokoo H, Nobusawa S.
  • Journal Title: Brain Pathol . Volume: 1 Issue: 3 Pages: 1-9
  • DOI: 10.1111/bpa.12943
  • Peer Reviewed / Open Access
• [Journal Article] Desmoplastic myxoid tumor, SMARCB1-mutant: a new variant of SMARCB1-deficient tumor of the central nervous system preferentially arising in the pineal region. (2021)
  • Author(s): Matsumura N, Goda N, Yashige K, Kitagawa M, Yamazaki T, Nobusawa S, Yokoo H.
  • Journal Title: Virchows Arch. Volume: 479 Issue: 4 Pages: 835-839
  • DOI: 10.1007/s00428-020-02978-3
  • Peer Reviewed
• [Journal Article] CNS low-grade diffusely infiltrative tumors with INI1 deficiency, possessing a high propensity to progress to secondary INI1-deficient rhabdoid tumors. (2020)
  • Author(s): Nobusawa S, Nakata S, Nakano Y, Kawamura A, Yoshida M, Tamura A, Hasegawa D, Kosaka Y, Ito I, Watanabe R, Oishi T, Hayashi N, Ishikawa E, Sakamoto N, Okura N, Murakami C, Ichimura K, Hirato J, Yokoo H.
  • Journal Title: Am J Surg Pathol Volume: 44 Issue: 11 Pages: 1459-1468
  • DOI: 10.1097/pas.0000000000001520
  • Peer Reviewed
• [Journal Article] Secondary INI1-deficient rhabdoid tumors of the central nervous system: analysis of four cases and literature review (2020)
  • Author(s): Nobusawa S, Nakata S, Yoshida Y, Yamazaki T, Ueki K, Amano K, Yamamoto J, Miyahara M, Sugai T, Nakazato Y, Hirato J, Yokoo H.
  • Journal Title: Virchows Archiv Volume: - Issue: 5 Pages: 763-772
  • DOI: 10.1007/s00428-019-02686-7
  • Peer Reviewed
• [Journal Article] Clinicopathological characteristics of circumscribed high-grade astrocytomas with an unusual combination of BRAF V600E, ATRX, and CDKN2A/B alternations (2019)
  • Author(s): Murakami Chiaki、Yoshida Yuka、Yamazaki Tatsuya、Yamazaki Ayako、Nakata Satoshi、Hokama Yohei、Ishiuchi Shogo、Akimoto Jiro、Shishido-Hara Yukiko、Yoshimoto Yuhei、Matsumura Nozomi、Nobusawa Sumihito、Ikota Hayato、Yokoo Hideaki
  • Journal Title: Brain Tumor Pathology Volume: 36 Issue: 3 Pages: 103-111
  • DOI: 10.1007/s10014-019-00344-z
  • Peer Reviewed
• [Remarks] 群馬大学大学院医学系研究科病態病理学分野
  • URL: http://humanpathol.dept.med.gunma-u.ac.jp/index.php