Carcinogenic mechanism of ovarian cancer and of examination of ovarian cancer by NGS analysis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09833
• 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: Keio University
• Principal Investigator: AKAHANE Tomoko 慶應義塾大学, 医学部(信濃町), 特任助教 (40398699)
• Co-Investigator(Kenkyū-buntansha): 山上 亘 慶應義塾大学, 医学部(信濃町), 講師 (30348718) ; 片岡 史夫 慶應義塾大学, 医学部(信濃町), 講師 (40306824)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 卵巣癌

Outline of Final Research Achievements

Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer. We analyzed DNA sequencing for TP53 variants of p53 signatures and STIC in RRSO and benign gynecologic disease. TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer. Those results were sugeested that sequence analysis for TP53 revealed 2 types of p53 signatures.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

2020年の人口動態統計の婦人科癌がん死亡者数データー報告は子宮体癌約2600人、子宮頸癌約2800人に対し卵巣癌は約4800人と約2倍となっている。このような状況にも関わらず、卵巣は検診対象臓器でないため卵巣癌の早期検出は困難であり有用な検査方法や腫瘍マーカーは現在も模索中である。卵巣癌だけでなく癌の早期検出は極めて重要な予後因子であり、卵巣癌もFIGOステージ分類Ⅰ期症例の5年生存率は90％を超える。本研究の実装化による卵巣癌早期検出は、婦人科癌全体の死亡者数の減少だけでなく化学療法における体力的、精神面などの患者自身の多方面にわたる負担および社会医療費負担の軽減へとつながる可能性がある。