2021 Fiscal Year Final Research Report
Comprehensive molecular analysis of pediatric glioma
Project/Area Number |
20K16873
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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Research Institution | The University of Tokyo |
Principal Investigator |
Nakano Yoshiko 東京大学, 医学部附属病院, 助教 (00796005)
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Project Period (FY) |
2020-04-01 – 2022-03-31
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Keywords | 小児脳腫瘍 / 神経膠腫 |
Outline of Final Research Achievements |
To reveal the molecular profile of pediatric glioma in Japan, 300 cases of pediatric glioma were analyzed in two years. Analyses included sequencing for hot spot mutations in H3, BRAF, IDH1, IDH2, TERT promoter, FGFR1, and RT-PCR for KIAA1549-BRAF for all cases and RNA sequencing and methylation analysis for selected cases, which were difficult to diagnose pathologically and showed atypical clinical course. Genetic abnormalities were detected in 53% of glioma cases through pyrosequencing or RT-PCR. The distribution of typical genetic abnormalities in each histological subtype was the same as that was reported previously from other international groups. Targetable BRAF V600E were detected in 45 cases and NTRK fusion was detected was detected not only in infantile hemispheric glioma but also CNS ganglioneuroblastoma. This suggest the importance of molecular analysis for pediatric glioma regardless of the histological diagnosis to find candidate for molecular targeted therapy.
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Free Research Field |
小児脳腫瘍
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Academic Significance and Societal Importance of the Research Achievements |
簡易な解析を行うことで小児神経膠腫の50%以上で診断に寄与し得る典型的な遺伝子異常が検出されるた。また、BRAF V600EやNTRK融合遺伝子は、神経膠腫に含まれる様々な病理組織型、さらには神経膠腫以外の病型とも鑑別の難しい症例からも検出された。さらに、次世代シークエンサーを用いることで、診断困難例の生物学的特徴も明らかにしすることができた。これらは、分子遺伝学的解析の実施の意義、すなわち、小児脳腫瘍における診断の精度の向上による適切な治療の選択、また分子標的薬を用いた予後の改善につながることを示唆している。
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