| Project/Area Number |
18K15108
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
YOSHIDA AKIHIKO 国立研究開発法人国立がん研究センター, 中央病院, 医員 (80574780)
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 肉腫 / 分類 / 病理診断 / 遺伝子変異 / 融合遺伝子 / 免疫組織化学 / 分類不能 / 分類不能肉腫 |
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| Outline of Final Research Achievements |
A small subset of bone and soft tissue tumors remain diagnostically challenging. We applied next-generation sequencing to these tumors and identified novel or emerging entities/subtypes, each of which is characterized by distinct phenotype and molecular genetics, including novel NTRK3 fusions, novel KMT2A fusions, EWSR1/FUS-CREB fusion, and RREB1-MRTFB fusion. We also defined clinically relevant novel tumor subsets, including H3K27me3-deficient dedifferentiated chondrosarcoma, malignant giant cell tumor of bone lacking H3F3A mutation, and BCOR-associated sarcoma in adults. Further, we discovered diagnostically useful findings in existing entities, such as FOS fusions/upregulation in proliferative fasciitis/myositis, an effective risk stratification model for epithelioid hemangioendothelioma, and frequent NKX3.1 overexpression in mesenchymal chondrosarcoma. These achievements have contributed significantly to the classification and accurate diagnosis of bone and soft tissue tumors.
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| Academic Significance and Societal Importance of the Research Achievements |
この研究によって、骨軟部に発生する分類困難な腫瘍のなかに、これまで知られていなかった新しい疾患単位や亜型を提唱・確立することができた。また既に知られた腫瘍型においても、臨床的に意義の大きなグループを新しく認識することができた。さらに、疾患の原因となる遺伝子異常、予後予測に有用なリスク分類、病理診断に有用な診断マーカーも発見することができた。これらの成果の大部分は世界で初めて得られた知見であり学術的意義が大きい。研究の成果により、分類不能・困難な骨軟部腫瘍症例が減少し、より正確な病理診断を行うことができ、医療の質が向上することが期待される。
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