Creation of novel tumor angiogenesis inhibitory therapy using hemangioblastoma specimens and VHL disease-specific iPS cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K16552
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: The University of Tokyo
• Principal Investigator: Takayanagi Shunsaku 東京大学, 医学部附属病院, 特任講師(病院)(助教) (90406489)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 血管芽腫 / VHL病 / iPS細胞 / 血管新生抑制

Outline of Final Research Achievements

In this study, we aimed to construct a novel anti-angiogenic therapy by analyzing hemangioblastoma surgical specimens of our department and VHL disease-specific iPS cells established from them. First, we performed a comprehensive methylation analysis of 20 hemangioblastoma cases. No new causative gene candidates were identified. Copy number analysis also showed the possibility that many copy number abnormalities were found in cases that followed a malignant course and were involved in malignant transformation. It was also found that hemangioblastomas may be divided into three groups by clustering analysis.
It has been confirmed that VHL disease-specific iPS cells can form hemangioblastoma-like tumors depending on the culture conditions, but it was difficult to stably culture them.

Free Research Field

脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究において、残念ながら有意な血管芽腫の新規原因遺伝子候補を同定する事は出来なかった。しかし、本研究において、悪性の経過をたどった症例で多数のコピー数異常が見つかり、従来は良性腫瘍と思われていた腫瘍であっても、コピー数異常により悪性の経過をたどる可能性が示された。また、クラスタリング解析により血管芽腫が３つのグループに分かれるかもしれない事がわかり、従来は単一と思われていた腫瘍であっても、別々の特徴をもった腫瘍である可能性が示された。良性腫瘍であるが血管新生旺盛である血管芽腫の様々な特徴が今回新たに判明し、今後の新規血管新生抑制療法開発につなげられる可能性があると思われる。