| Project/Area Number |
17K10856
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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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| Research Field |
Neurosurgery
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| Research Institution | Yamagata University |
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Principal Investigator |
Sonoda Yukihiko 山形大学, 大学院医学系研究科, 教授 (90302140)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 膠芽腫 / 再発形式 / CD133 / TERT / PTEN / 生存期間 / Glioblastoma / recurrence pattern / IDH / multifocal / distrant recurrence / SVZ / Cancer stem cell / 遠隔再発 / 腫瘍幹細胞 |
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| Outline of Final Research Achievements |
We analyzed 153 cases of primary glioblastoma to identify molecular markers associated with pattern of recurrence. TERTp-mutant glioblastoma was strongly associated with multifocal/distant lesions. TERTp mutations, the expression of CD133, and PTEN deletion were significantly associated with multifocal lesions. TERTp mutations were positively correlated with EGFR amp/gain, CDKN2A deletion, and PTEN deletion; however, these mutations were negatively correlated with PDGFR amp/gain, CDK4 gain and TP53 deletion. Less aggressive glioblastoma with TERTp wild type may be a distinct clinical and molecular subtype of IDH wild type GBM.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は大多数が局所再発をきたし予後不良とされる、膠芽腫の中で従来まれとされてきた遠隔再発に着目し、再発形式に関与する因子を明らかにしたものである。結果としてPTEN遺伝子異常、TERTp変異、CD133の3つの因子は膠芽腫の再発形式に強く関与していることを初めて明らかにした。本研究により、膠芽腫の後療法は現在 局所再発のみを対象に行われているが、今後上記3因子をもつ腫瘍に関しては、遠隔再発を念頭においた治療を行うなど、今後の個別化医療につながる可能性が示唆され、社会的意義が大きいと考えられる。
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