comprehensive gene mutation profiling in liquid biopsy from gynecological cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16776
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Iwahashi Naoyuki 和歌山県立医科大学, 医学部, 助教 (50750907)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: リキッドバイオプシー / 婦人科癌

Outline of Final Research Achievements

Liquid biopsies of circulating tumor DNA (ctDNA) can detect tumor-specific molecular alterations and have been used as a non-invasive diagnostic, prognostic, and predictive tool. We investigated comprehensive gene mutation profiling in gynecological cancer utilizing plasma ctDNA. We examined the mutation profiles of plasma ctDNA samples obtained from 50 gynecological cancers (31 ovarian cancers, 5 endometrial cancers, 4 cervical cancers, and 10 other rare pathological types of cancer) by CAPP-seq, a novel ultrasensitive NGS-based approach, with AVENIO ctDNA Surveillance Kit (197genes). Among 50 cancers, 49 (98%) harbored one or more non-synonymous somatic mutation. The most frequently altered genes were TP53 (38%), APC (22%), KRAS (22%), EGFR (14%). These findings suggest that characterization of the genetic profiles of independent tumors using plasma ctDNA may lead to the development of novel personalized treatment strategies in gynecological cancer.

Free Research Field

産婦人科学関連

Academic Significance and Societal Importance of the Research Achievements

進行婦人科癌の長期予後は不良であり、今後の婦人科癌の治療戦略として、患者個々の遺伝子変異プロファイルに合わせた適切な抗癌剤・分子標的薬の選択が予後の改善に重要となる。　Liquid Biopsyにより新たな標的遺伝子を同定し、婦人科悪性腫瘍における治療標的遺伝子のメカニズムを解明することにより、既存の抗癌剤や分子標的薬の感受性も含めた新たな治療戦略の検討や、　新規分子標的薬の開発へと発展させることができ、本研究は新規Precision medicine治療の推進のために意義の大きな研究と考えられる。