Aberrant histone modification patterns of tumor-related gene promoter as a new biomarker for renal cell carcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09150
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Keio University
• Principal Investigator: SHINOJIMA Toshiaki 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (60306777)
• Co-Investigator(Kenkyū-buntansha): 水野 隆一 慶應義塾大学, 医学部(信濃町), 准教授 (60383824)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 腎細胞癌 / エピジェネティクス / 遺伝子変異 / 腫瘍免疫

Outline of Final Research Achievements

Recent high-throughput profiling of renal cell carcinomas (RCC) has identified a recurrent mutation including chromatin regulators, such as genes involved in the chromatin remodeling or in histone modifications. In this study, using a chromatin immunoprecipitation assay, we found that there was a significant difference in active modification patterns in the promoter region of HIF2A, which is a potent oncogenic driver in RCC. The mutation in chromatin regulators, did not affect the pathological tumor grade nor T stage; however, it revealed to be an independent significant factor that affect overall and progression free survival of RCC patients. Moreover, some molecular markers of immune cells was significantly decreased in the tumor samples harboring the mutation, suggesting the interaction of chromatin regulators and tumor-immune system.

Free Research Field

医歯薬系

Academic Significance and Societal Importance of the Research Achievements

手術時に転移を認めない症例でも、従来の病理診断にエピジェネティクス関連遺伝子変異の有無を加味することは、フォローアップスケジュールの決定や術後補助療法の必要性の判断などに有用な可能性があり、臨床での応用が期待される。また、転移や再発のリスクが高い非転移性腎細胞癌の術後補助療法に、腫瘍免疫を制御する薬物療法が有効である可能性が示唆されたことは、今後の発展が大いに期待される知見である。