Analysis of intra-tumoral heterogeneity of actionable genetic variations in Ovarian Clear Cell Carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16874
• 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: Jikei University School of Medicine
• Principal Investigator: Takenaka Masataka 東京慈恵会医科大学, 医学部, 講師 (00433988)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 卵巣明細胞癌 / 腫瘍内不均一性 / 次世代シークエンス

Outline of Final Research Achievements

The objective of the study was to clarify the intratumoral heterogeneity of treatment-related gene alteration in clear cell carcinoma of the ovary. The subjects were fifty-seven primary of metastatic lesions resected from nine cases in the initial surgery. Thirty-eight types of gene mutations were detected in eighteen genes. Pathogenic mutations in ARID1A and PIK3CA were identified in five of nine cases, respectively. Moreove, presence intratumoral heterogeneity was suspected in ARID1A and PIK3CA gene alterations in comparison of primary and metastatic lesions. From the results, it was suggested that it is necessary to pay attention to intratumoral heterogeneity when performing treatment targeting these genes in personalized medicine for clear cell carcinoma.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

がんの薬物療法は、従来の殺細胞性抗がん剤に加えて、がん細胞で生じている遺伝子異常を標的とした分子標的治療薬が臨床現場で徐々に使用され始めている。それに伴い、遺伝子異常の腫瘍内不均一性は薬剤抵抗性に関与するとの報告もあり、今後は腫瘍内不均一性を考慮した治療薬の選択が求められる可能性がある。本研究では日本人に多く発生し、進行症例では極めて予後不良な卵巣明細胞癌の腫瘍内不均一性を調査し、一部の治療関連遺伝子異常で腫瘍内不均一性が生じている可能性を示した。