Novel therapeutic strategy for ovarian cancer based on the comprehensive gene mutation analysis using circulating tumor DNA

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09626
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Ino Kazuhiko 和歌山県立医科大学, 医学部, 教授 (60303640)
• Co-Investigator(Kenkyū-buntansha): 西尾 和人 近畿大学, 医学部, 教授 (10208134) ; 岩橋 尚幸 和歌山県立医科大学, 医学部, 助教 (50750907)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 卵巣癌 / リキッドバイオプシー / 網羅的遺伝子プロファイリング / 血中循環腫瘍DNA

Outline of Final Research Achievements

Liquid biopsies using circulating tumor DNA (ctDNA) have been used as non-invasive diagnostic tool for detecting cancer-specific gene mutations. In the present study, we performed the comprehensive gene mutation profiling of ctDNA in patients with ovarian cancer, and investigated their association with clinicopathological and prognostic factors. The ctDNA extracted from patients’ plasma were analyzed using CAPP-Seq. The most frequently mutated genes were as follows: TP53 in high-grade serous carcinoma, APC in clear cell carcinoma, PIK3CA in endometrioid carcinoma, and KRAS in mucinous carcinoma. Higher ctDNA concentration significantly correlated with worse progression-free survival (PFS). Further, patients with any pathogenic mutations showed significantly worse PFS. These findings suggest that ctDNA-based gene profiling might help in establishing personalized therapeutic strategies for ovarian cancer.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究において、卵巣癌患者の血中循環腫瘍DNA（ctDNA）による遺伝子プロファイリングを実現し、予後予測に有用であるのみでなく、術前化学療法前後のctDNA遺伝子変異のモニタリングによりクローン選択/進化を検出できた。これらの結果は今後の卵巣癌の個別化医療の治療戦略に貢献し、従来の組織DNA解析に勝るctDNAリキッドバイオプシーの有用性を示唆した。