| Project/Area Number |
18K07828
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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 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Jichi Medical University |
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Principal Investigator |
Morimoto Akira 自治医科大学, 医学部, 客員教授 (30326227)
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| Co-Investigator(Kenkyū-buntansha) |
翁 由紀子 自治医科大学, 医学部, 非常勤講師 (30438650)
早瀬 朋美 自治医科大学, 医学部, 客員研究員 (50433587)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | ランゲルハンス細胞組織球症 / 分裂促進因子活性化タンパク質キナーゼ / BRAF V600E変異 / 予後因子 / MAP2K1変異 |
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| Outline of Final Research Achievements |
In a retrospective cohort of 59 patients (50 children, 9 adults), 46% had BRAF V600E mutation. In a prospective cohort of 104 patients (aged <20 years), 40.4% had BRAF V600E mutation, 6.7% had BRAF indel, and 31.7% had MAP2K1 mutation. BRAF V600E mutation was significantly more common in patients with a disease activity score (DAS) of 7 or more (76.9% vs. 38.5%, p=0.014).No association was found between genetic variants and sex, age at diagnosis, disease type, initial treatment response, event-free survival, overall survival, or CNS-related complications in any cohort.
BRAF V600E mutation was associated with DAS but not outcomes of LCH.
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| Academic Significance and Societal Importance of the Research Achievements |
LCH細胞にはMitogen-activated Protein Kinase経路の遺伝子に相互排他的な発がん性変異があることが報告され、BRAF V600E変異は最も高頻度な変異で50%前後の例に見いだされる。欧米では、BRAF V600E変異は、高リスク（高い病勢スコア(DAS)・高い再発率・高い中枢神経関連続発症頻度）と報告されている。しかし、日本のシタラビン中心の治療を受けた患者においては、BRAF V600E変異は、DASが高いこととは関連するが転帰とは関連せず、BRAF V600Eの有無により治療を層別化する意義は低いことが分かった。
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