Novel therapeutic strategy based on XCL1 expression for squamous cell carcinoma arising from mature cystic teratoma of the ovary

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16785
• 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: Niigata University
• Principal Investigator: Tamura Ryo 新潟大学, 医歯学総合研究科, 客員研究員 (70650620)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 卵巣成熟奇形腫悪性転化 / 腫瘍内不均一性 / 全エクソンシーケンス / APOBEC / 免疫チェックポイント阻害薬

Outline of Final Research Achievements

In this study, we clarified the spatial genomic diversity and clonal evolution in squamous cell carcinoma arising from ovarian teratoma by performing a comprehensive genomic analysis of multiple sites. We also revealed that APOBEC signature mutations are common in this disease. To elucidate the mechanism of malignant transformation, we focused on the noncancerous parts of the disease, specifically evaluating the squamous epithelium in both squamous cell carcinoma and mature teratoma cases. After selectively sampling these epithelia, we comprehensively evaluated their genetic abnormalities and found that TP53 mutations and APOBEC-mediated mutations were involved in malignant transformation.

Free Research Field

産婦人科

Academic Significance and Societal Importance of the Research Achievements

卵巣成熟奇形腫悪性転化症例が、組織所見毎に強い腫瘍内不均一性を有することは、本疾患の治療抵抗性の強さに関連している可能性が高く、また実臨床での腫瘍の採取部位や遺伝子異常の評価に注意を促す重要な結果であると考えられる。また、非癌部を含めた解析により、TP53変異やAPOBEC型変異の蓄積が悪性転化に関与していることを見出したことは、今後本疾患の早期発見や治療に結びつく可能性があり、臨床的意義が大きいと考えられる。