Aberrant chromatin remodeling induced by super-enhancer formation in malignant glioma

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09478
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Nagoya University
• Principal Investigator: Ohka Fumiharu 名古屋大学, 医学系研究科, 講師 (10725724)
• Co-Investigator(Kenkyū-buntansha): 夏目 敦至 名古屋大学, 未来社会創造機構, 特任教授 (30362255)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: Brain tumor / Glioma mouse model / Epigenetic alteration

Outline of Final Research Achievements

Despite the accumulation of big data, the mechanism of tumorigenesis of most malignant brain tumors is still unclear, and it is essential to explore novel mechanistic concepts that have never been explored before. Epigenomic mechanisms are precisely regulated by modifications that activate (on) and repress (off) gene expression, and an imbalance between these modification contributes to cancer development. Recently, super-enhancer formation has been proposed as a novel driver mechanism of cancer, in which transcription factors such as Myc molecules alter the three-dimensional structure of the genome and enhance gene expression of cancer-related genes. In this study, we will elucidate the abnormal chromatin conformational changes during tumor formation using a mouse model which spontaneously develops brain tumor.

Free Research Field

脳腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究ではこれまで研究モデルが限られていた脳腫瘍分野で新規性の高い脳腫瘍自然発生マウスモデルを用いて、脳腫瘍形成過程における経時的な解析を行うことができる点で意義が大きいものと考える。脳腫瘍ではこれまで腫瘍検体を用いた網羅的解析が主に進められてきたが、腫瘍検体を用いた解析では悪性転化した結果を見ている可能性があり、腫瘍形成過程を経時的に解析することは困難である。前腫瘍細胞の段階からGFPでトレースできる本モデルを用いてダイナミックなエピゲノム異常の解明を試みることで、新規治療戦略につながる可能性があるものと考える。