Comparative genetic analysis of central nervous system lymphomas between sites in the central nervous system or extracranial organs
| Project/Area Number |
18K08950
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Kyorin University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
市村 幸一 国立研究開発法人国立がん研究センター, 研究所, 分野長 (40231146)
永根 基雄 杏林大学, 医学部, 教授 (60327468)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 中枢神経系悪性リンパ腫 / 二次性中枢神経系悪性リンパ腫 / 遺伝子変異解析 / メチル化アレイ / 二次性悪性リンパ腫 / 脳腫瘍 / 分子遺伝子学 |
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| Outline of Final Research Achievements |
In order to search for mutations of central nervous system (CNS) lymphomas which might serve as driver mutations in the CNS, we have performed targeted sequencing in paired samples from four secondary central nervous system lymphoma (SCNSL) cases and two systemic relapse of primary central nervous system (PCNSL) cases. Mutational profiles were compared between the primary and recurrent tumor. MYD88, CD79B and PIM1 mutations were observed as shared mutations in all cases, therefore seemed to be relatively early genetic events. In the SCNSL cases, several de novo mutations were enriched only among the recurrent CNS tumors. One of those mutations were observed in 3/4 (75%) cases, and two mutations were observed in 2/4 (50%) cases. It is suggested that these de novo mutations in the recurrent CNS tumors might serve as driver mutations in the CNS. Further analysis in larger cohorts, and functional studies are required in order to validate these findings.
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| Academic Significance and Societal Importance of the Research Achievements |
PCNSL全身性再発、SCNSLに関する遺伝学的解析はその希少性から、特にPCNSL全身性再発、SCNSLの両者を解析し比較検討した報告は少ない。今回複数の遺伝子異常がDLBCLの中枢神経系病変に特徴的であることが示唆されたことはPCNSL、SCNSLの病態解明に寄与するとともに、予後不良であるこれらの疾患における治療標的としての検討につながる社会的意義がある。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Phase I/II study of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, in relapsed/refractory primary central nervous system lymphoma2021
Author(s)
Narita Y, Nagane M, Mishima K, Terui Y, Arakawa Y, Yonezawa H, Asai K, Fukuhara N, Sugiyama K, Shinojima N, Kitagawa J, Aoi A, Nishikawa R.
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Journal Title
Neuro Oncol
Volume: 23
Issue: 1
Pages: 122-133
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Consecutive single-institution case series of primary central nervous system lymphoma treated by R-MPV or high-dose methotrexate monotherapy2020
Author(s)
Sasaki N, Kobayashi K, Saito K, Shimizu S, Suzuki K, Lee J, Yamagishi Y, Shibahara J, Takayama N, Shiokawa Y, Nagane M
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Journal Title
Jpn J Clin Oncol
Volume: inpress
Issue: 9
Pages: 1-11
DOI
Related Report
Peer Reviewed
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[Presentation] JCOG1114C randomized phase III trial for newly-diagnosed PCNSL comparing HD-MTX + WBRT vs. HD-MTX + WBRT/TMZ followed by adjuvant TMZ2020
Author(s)
Nagane M, Fukumura K, Ueno T, Lee J, Shishido-Hara Y, Mishima K, Ichimura K, Mukasa A, Narita Y, Aburatani H, Nishikawa R, Mano H
Organizer
2020 International PCNSL Collaborative Group Virtual Meeting
Related Report
Int'l Joint Research
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[Presentation] Combined rituximab, methotrexate, procarbazine, vincristine, and cytarabine (R-MPV-A) treatment for patients with relapsed primary CNS lymphoma2020
Author(s)
Motoo Nagane, Nobuyoshi Sasaki, Keiichi Kobayashi, Kuniaki Saito, Daisuke Shimada, Yoshie Matsumoto, Shohei Iijima, Yuki Yamagishi, Saki Shimizu, Yuta Sasaki, Nobuyuki Takayama, Yoshiaki Shiokawa
Organizer
25th Annual Meeting of the Society for Neuro-Oncology
Related Report
Int'l Joint Research
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