Identification of causative genes for hemangioblastoma to elucidate the mechanisms of neovascularization and to develop novel therapeutic strategies

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670636
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: The University of Tokyo
• Principal Investigator: Mukasa Akitake 東京大学, 医学部附属病院, 講師 (90463869)
• Co-Investigator(Renkei-kenkyūsha): SAITO Kuniaki 杏林大学, 医学部, 助教 (50446564) ; NAKAMURA Eijiro 京都大学, 医学系研究科, 准教授 (90293878) ; NIWA Akira 京都大学, 医学系研究科, 助教 (20546999)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 血管芽腫 / VHL病 / 腫瘍血管新生 / 癌抑制遺伝子

Outline of Final Research Achievements

This study aimed to identify novel genes related to neovascularization through genetic analysis of hemangioblastomas, which have remarkable tumor-related vasculature. We collected 32 hemangioblastomas and subjected them to genetic and methylation analysis, mostly of the VHL gene. As a result, we found that 2-hit inactivation of the VHL gene is frequent in both VHL disease-related and sporadic hemangioblastomas. Of special note was that in sporadic cases, VHL inactivation by promoter region methylation and loss of heterozygosity of chromosomes 6 and 10 were more frequent than in VHL disease-related HB. In renal cell carcinoma, which frequently occurs in VHL disease patients, there is often alteration of the PBRM1 and BAP1 genes in addition to the VHL inactivation. However, these gene mutations were not observed in our HB cases.

Free Research Field

脳腫瘍