| Project/Area Number |
22K20799
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0901:Oncology and related fields
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
Hori Yoshikazu 和歌山県立医科大学, 医学部, 助教 (80963727)
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 濾胞性リンパ腫 / 形質転換 / リキッドバイオプシー / cfDNA / NGS / cell free DNA |
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| Outline of Research at the Start |
濾胞性リンパ腫の形質転換に関わる遺伝子変異をリキッドバイオプシーで検出できるかを検討する。具体的には、末梢血中のcell free DNAを濾胞性リンパ腫の患者で検出できるかを検討する。検出できた場合は次世代シークエンサーを用いて濾胞性リンパ腫の形質転換に関連すると報告されている遺伝子を検出できるかを検討し、可能であれば診断時の組織と比較し、濾胞性リンパ腫の診断、治療効果を判定できる系の確立を目指す。
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| Outline of Final Research Achievements |
We examined gene mutations associated with the transformation of follicular lymphoma (FL) using liquid biopsy. In transformed FL, the amount of cfDNA extracted was significantly higher even after adjusting for tumor burden. In this study, cfDNA at 82.8 ng was determined to be the value that stratified the transformation. Next-generation sequencing analysis using cfDNA revealed that the ratio of gene mutations, excluding TP53, was comparable to the genes extracted from previously reported FL lesions. On the other hand, TP53 mutations were significantly more frequent than previously reported. Interestingly, although there was no significant difference in the ratio of TP53 mutations between transformed and non-transformed cases, the VAF was significantly higher in transformed FL. This fact suggests that TP53 mutation-positive subclones exist in non-biopsied sites of FL from the time of diagnosis and that these subclones may increase as significant clones as transformation occurs.
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| Academic Significance and Societal Importance of the Research Achievements |
血液検査を行うことで、濾胞性リンパ腫に関連する遺伝子変異が検討できる可能性が示唆された。また、TP53変異の変異割合と、抽出されるcfDNA量を検討することで潜在的に存在する予後不良な形質転換濾胞性リンパ腫の存在を確認できる可能性があることも判明した。また、遺伝子の解析によりTP53の変異割合の拡大が濾胞性リンパ腫の形質転換と重要な関連がある可能性が判明したことから、今後はより検討する症例数を増やしてTP53の変異と形質転換の関係性について検討していきたいと考えている。
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