2018 Fiscal Year Final Research Report
Methylation dependent down-regulation of G0S2 leads to suppression of invasion and improved prognosis of IDH1-mutant glioma
| Project/Area Number |
17K16644
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurosurgery
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| Research Institution | Osaka University |
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Principal Investigator |
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| Research Collaborator |
Yamashita Toshihide
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Keywords | 神経膠腫 / IDH変異 / 浸潤 |
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| Outline of Final Research Achievements |
Isocitrate dehydrogenase (IDH) mutations are a prognostic factor in diffuse glioma. However, the mechanism by which these mutations improve prognosis are not clear. In a subset of IDH-mutant glioma, remodeling of the methylome results in the glioma-CpG island methylator phenotype (G-CIMP) and transcriptional reorganization. In this study, we focus on G0/G1 switch 2 (G0S2), which is highly downregulated in G-CIMP glioma. We found that G0S2 expression tended to increase as the WHO grade increased, and G0S2 knockdown inhibited glioma invasion. In addition, the stereotactic delivery of glioma cells with decreased G0S2 expression in the mouse brain resulted in prolonged survival. The Cancer Genome Atlas (TCGA) analysis also indicated that survival is longer in the lower G0S2 expression group than in the higher G0S2 expression group. These results provide one explanation for the improved survival in IDH1-mutant glioma as well as a new epigenetic target for glioma treatment.
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| Free Research Field |
脳神経外科
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| Academic Significance and Societal Importance of the Research Achievements |
神経膠腫は難治性原発性中枢神経系腫瘍であり、最も悪性度が高い膠芽腫の平均生存期間は16.8ヶ月と短い。二次性膠芽腫は、de novo膠芽腫に比べてイソクエン酸脱水素酵素(IDH)変異を多く認め、予後が良いことが知られていたが、IDH変異群で予後が良い機序は解明されていなかった。本研究の結果により、IDH変異型神経膠腫では高メチル化によってG0S2の発現が低下して細胞浸潤が抑制され、予後が改善していると考えられ、IDH変異型神経膠腫の予後が良い理由の一端を解明した。これらの結果は難治性神経膠腫の病態解明に役立つものと思われる。
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