2021 Fiscal Year Final Research Report
Development of therapeutic strategies for angiosarcoma of the scalp and face based on genome-wide analysis of tumor somatic mutation pattern
| Project/Area Number |
20K17323
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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 53050:Dermatology-related
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | 頭部血管肉腫 / エクソーム解析 / 免疫チェックポイント阻害剤 / ドライバー変異 / Mutational signature / 次世代シーケンサー / 遺伝子変異 |
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| Outline of Final Research Achievements |
In this study, we attempted tumor driver mutation identification, tumor mutation burden quantification, and mutational signature analysis based on exome analysis of head angiosarcoma tissue samples. The frequency of C>T substitutions was extremely high in 8 cases, and a strong bias was observed. This was considered to be an artifact that occurred during the preparation or storage of the formalin fixed paraffin embedded tissue samples, and these 8 cases were deemed unsuitable for analysis. As an alternative analysis method, we decided to focus on specific cancer-related genes using cancer panel sequencing. Currently, sequencing of 8 cancer panel samples has already been completed. The analysis is currently underway with the particular goal of identifying tumor driver mutations.
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| Free Research Field |
皮膚科学
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| Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント阻害剤は予後不良な頭部血管肉腫に対して有望な治療薬と期待される。その奏効率は遺伝子変異量定量に相関するとされ、本研究により頭部血管肉腫の遺伝子変異量の傾向を明らかにすることで、免疫チェックポイント阻害剤の有用性の予測が期待できる。腫瘍ドライバー遺伝子は低分子阻害剤や抗体医薬などの分子治療の標的となり得、その同定は治療法開発の重要な足掛かりとなる。頭部血管肉腫は沖縄県で多発する地域特異性の高い疾患であり、現在でもその罹患患者数は増加傾向にある。その疾患メカニズムの解明や候補治療薬の選定は、疾患の地域特異性の原因解明や、沖縄県の一つの医療課題の解決につながると考えられる。
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