| Project/Area Number |
17K08710
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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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| Research Field |
Human pathology
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Mori Taisuke 国立研究開発法人国立がん研究センター, 中央病院, 医員 (00296708)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 頭頸部扁平上皮癌 / ゲノム診断 / p53 / 次世代シークエンス / TP53 / 全エクソンシークエンス / 遺伝子全エクソン解析 / 病理診断 / 頭頸部腫瘍 / ゲノム解析 |
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| Outline of Final Research Achievements |
This study was designed to investigate whether protein phenotype analysis via preoperative biopsy specimens and mutation status analysis via surgical specimens could determine surgical margin distances and predict clinical outcomes. The findings of the study accurately predicted clinical outcomes using formalin-fixed, paraffin-embedded biopsies or surgical specimens, except in patients with HPV-associated SCC. We categorized TP53 mutation as p53 protein phenotype 2+, lost as p53 adverse functions, TP53 wild-type and TP53 mutation as p53 protein phenotype +, and ± as p53 favorable functions. As a result, p53 adverse functions remained an independent prognostic factor for overall survival, local control, and distant metastases-free survival in enrolled patients. Moreover,local recurrence rates after adequate surgical margins were higher.Therefore,larger surgical margin distances were required for patients.
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| Academic Significance and Societal Importance of the Research Achievements |
TP53などの腫瘍抑制遺伝子のゲノムおよびタンパク質レベルを分析する詳細な方法としてTP53エキソン配列全体の状態とp53タンパク質の表現型を詳細に調べる本研究開発は、頭頸部扁平上皮癌の生物学的特性を把握するのに効果的であった。ゲノム解析に関するさらなる技術革新は、生検標本から術前のマイクロサンプルを使用して腫瘍の生物学的特性を予測するのに役立ち、この情報は、個別の外科治療の戦略を立て、外科的マージン距離の決定を可能にすると考えられた。
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