Newly proposed high-grade CNS tumor entities
Project/Area Number |
19K16579
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 49020:Human pathology-related
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Research Institution | Gunma University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 脳腫瘍 / INI1/SMARCB1 / ependymoma / AT/RT / epithelioid glioblastoma / 遺伝子 / 病理 |
Outline of Research at the Start |
脳腫瘍は小児腫瘍の中では最も発生頻度が高く、病理診断が難しいとされる腫瘍の一つである。近年、小児脳腫瘍の領域においても大規模な分子遺伝学的研究によって様々な遺伝子異常が報告され、生物学的特性に関する多くの知見が明らかになり、病理組織学的・分子遺伝学的特徴を統合した疾患概念の構築が進んでいる。しかし、最近になって認識され、頻度が低く、診断に難渋するような腫瘍の病態解明は遅れており、正確な診断や適切な治療に繋がらない症例も多い。我々はこのような腫瘍を、多角的に解析し、生物学的理解を深め、疾患群としての輪郭を明確にしていく。
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Outline of Final Research Achievements |
1) We identified hitherto unclassifiable tumors, for which we propose the designation of central nervous system low-grade diffusely infiltrative tumors with INI1 deficiency (CNS LGDIT-INI1). CNS LGDIT-INI1 may be clinically indolent but have a high propensity to progress secondarily to agrresive rhabdoid tumors. 2) We reported hitherto histopathologically unclassifiable high-grade tumors, under the tentative label of ependymoma-like tumors with mesenchymal differentiation (ELTMD), harboring C11orf95-NCOA1/2 or -RELA fusion. t-distributed stochastic neighbor embedding analysis of DNA methylation data from cases with C11orf95-NCOA1/2 and a reference set of other CNS tumors revealed that these cases were clustered together and were distinct from all subgroups of ependymomas. Although ELTMD exhibited morphological and genetic associations with supratentorial ependymoma with C11orf95-RELA, they cannot be regarded as ependymoma.
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Academic Significance and Societal Importance of the Research Achievements |
本研究で見出された新規腫瘍はいずれも希少なもので、診断困難で予後不良である。これらの腫瘍がWHO分類などの国際分類に記載され、広く認識されることにより、今後多数の症例が収集され、網羅的な分子遺伝学的検索を含めた多角的な解析が進むことにより、生物学的理解が深まり、疾患群としての輪郭が明確になっていくことが期待される。正確な診断と適切な臨床的マネージメント、更には今後の治療法の確立に繋がると考える。
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Report
(3 results)
Research Products
(3 results)
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[Journal Article] Ependymoma-like tumor with mesenchymal differentiation harboring C11orf95-NCOA1/2 or -RELA fusion: A hitherto unclassified tumor related to ependymoma2021
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.
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Journal Title
Brain Pathol .
Volume: 1
Issue: 3
Pages: 1-9
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Am J Surg Pathol
Volume: 44
Issue: 11
Pages: 1459-1468
DOI
Related Report
Peer Reviewed
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[Journal Article] Secondary INI1-deficient rhabdoid tumors of the central nervous system: analysis of four cases and literature review2020
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.
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Journal Title
Virchows Archiv
Volume: -
Issue: 5
Pages: 763-772
DOI
Related Report
Peer Reviewed