Risk of distant recurrence based on ctDNA analysis by NGS platform with molucular barcode

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15591
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Osaka University
• Principal Investigator: Yoshinami Tetsuhiro 大阪大学, 医学部附属病院, 特任助教(常勤) (30894240)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ctDNA / breast cancer / clinical implementation

Outline of Final Research Achievements

In this research, ctDNA analysis was performed on five patients experiesed distant recurrence after radical surgery, using stored plasma samples obtained at the time of initial diagnosis. No tumor-informed assay, which can detect ctDNA without genomic profiling data from tumor tissues, is used as ctDNA analysis in the current research. The assay revealed that four patients had positive-ctDNA, indicating that detectable ctDNA at initial diagnosis was one of the features in patients wiht distant recurrence. This data is valuable because there are few reports about it with no tumor-informed assay. Moreover, in all four patients, no mutaitons such as base substitution, or insertion/deletion, were idenified, and cancer-spesicif methlyation were detected. Epigenomic profiling enables to improve the sensitivity of ctDNA analysis for the evaluation of risk on distant recurrent. The results of this research will be presented at Japanese Breast Cancer society 2024.

Free Research Field

乳癌におけるctDNA解析の臨床導入

Academic Significance and Societal Importance of the Research Achievements

現在、遠隔再発リスク診断には腫瘍組織のゲノムプロファイリング結果を利用するctDNA検査が主流であるが、一定の割合でそれが不成功となる症例がある。本研究で用いた検査は、組織の事前検査は不要で、すべての患者を対象とすることができる。加えて、事前の腫瘍組織検査が必要ない分、ctDNA解析結果の受領までの時間が短く、治療方針の決定にすみやかに結果を利用できる。このような明らかな患者へのメリットがある検査の臨床導入につながる研究成果であると考える。さらに、ctDNA解析におけるエピゲノムプロファイリングの重要性を臨床検体を用いて評価した研究は現時点では多くなく学術的意義が高い。