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

Research Project

Project/Area Number 26670636
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionThe University of Tokyo

Principal Investigator

Mukasa Akitake  東京大学, 医学部附属病院, 講師 (90463869)

Co-Investigator(Kenkyū-buntansha) 田中 將太  東京大学, 医学部附属病院, 助教 (80643725)
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
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (21 results)

All 2017 2016 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (3 results)

  • [Journal Article] Development of Database and Genomic Medicine for von Hippel-Lindau Disease in Japan2017

    • Author(s)
      Takayanagi S, Mukasa A, Nakatomi H, Kanno H, Kuratsu JI, Nishikawa R, Mishima K, Natsume A, Wakabayashi T, Houkin K, Terasaka S, Yao M, Shinohara N, Shuin T, Saito N.
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 57 Issue: 2 Pages: 59-65

    • DOI

      10.2176/nmc.ra.2016-0206

    • NAID

      130005394576

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differences in genetic and epigenetic alterations between von Hippel-Lindau disease-related and sporadic hemangioblastomas of the central nervous system.2017

    • Author(s)
      Takayanagi S, Mukasa A, Tanaka S, Nomura M, Omata M, Yanagisawa S, Yamamoto S, Ichimura K, Nakatomi H, Ueki K, Aburatani H, Saito N
    • Journal Title

      Neuro Oncol.

      Volume: 印刷中 Issue: 9 Pages: 1-7

    • DOI

      10.1093/neuonc/nox034

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 血管芽腫とVHL遺伝子解析2016

    • Author(s)
      高柳 俊作、武笠 晃丈、中冨 浩文、齊藤 延人
    • Journal Title

      Clinical Neuroscience

      Volume: 34 Pages: 1052-1053

    • Related Report
      2016 Annual Research Report
  • [Journal Article] von Hippel-Lindau病2015

    • Author(s)
      高柳 俊作、武笠 晃丈、中冨 浩文、齊藤 延人
    • Journal Title

      Clinical Neuroscience

      Volume: 33 Pages: 433-436

    • Related Report
      2015 Research-status Report
  • [Presentation] 次世代シークエンサなどを用いた中枢神経系血管芽腫の統合的解析2016

    • Author(s)
      髙柳俊作、武笠晃丈、野村昌志、田中将太、中冨浩文、油谷浩幸、市村幸一、齊藤延人
    • Organizer
      第34回日本脳腫瘍学会学術集会
    • Place of Presentation
      甲府富士屋ホテル (山梨県・甲府市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Integrated genomic analysis for von Hippel-Lindau disease-related2016

    • Author(s)
      Shunsaku Takayanagi, Akitake Mukasa, Masashi Nomura, Shunsuke Yanagisawa, Shota Tanaka,Hirofumi Nakatomi, Hiroyuki Aburatani, Koichi Ichimura, Keisuke Ueki, Nobuhito Saito
    • Organizer
      21st Annual Meeting of the Society for Neuro-oncology
    • Place of Presentation
      Fairmont Scottsdale Princess Hotel (Scottsdale Arizona, USA)
    • Year and Date
      2016-11-19
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] von Hippel-Lindau病症例に対する多角的・集学的診療の取り組み2016

    • Author(s)
      高柳俊作、中冨浩文、野村征司、吉野正紀、金太一、武笠晃丈、辛正廣、齊藤 延人
    • Organizer
      第21回日本脳腫瘍の外科学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京都・港区)
    • Year and Date
      2016-09-29
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 中枢神経系血管芽腫非VHL病症例におけるVHL遺伝子変異の重要性ー次世代シークエンサを用いた検討ー2016

    • Author(s)
      高柳俊作、武笠晃丈、野村昌志、田中将太、中冨浩文、油谷浩幸、市村幸一、齊藤延人
    • Organizer
      日本脳神経外科学会第75回学術総会
    • Place of Presentation
      福岡国際会議場(福岡県・福岡市)
    • Year and Date
      2016-09-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] 次世代シークエンサを用いた中枢神経系血管芽腫におけるVHL遺伝子解析2016

    • Author(s)
      高柳俊作、武笠晃丈、野村昌志、田中将太、中冨浩文、油谷浩幸、市村幸一、齊藤延人
    • Organizer
      第17回日本分子脳神経外科学会
    • Place of Presentation
      帝京大学板橋キャンパス本部棟 臨床大講堂(東京都・板橋区
    • Year and Date
      2016-09-10
    • Related Report
      2016 Annual Research Report
  • [Presentation] VHL病における厚労省班会議の活動とゲノム医療の展開2016

    • Author(s)
      高柳俊作、武笠晃丈、中冨浩文、菅野洋、矢尾正祐、執印太郎、齊藤延人
    • Organizer
      第22回日本家族性腫瘍学会学術集会
    • Place of Presentation
      ひめぎんホール(愛媛県・松山市)
    • Year and Date
      2016-06-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] Infantile myofibromatosisにおける新規原因遺伝子PDGFRB の解析2015

    • Author(s)
      高柳 俊作、田中 将太、野村 昌志、武笠 晃丈、辛 正廣、中冨 浩文、樋渡 光輝、滝田 順子、齊藤 延人
    • Organizer
      第33回日本脳腫瘍学会
    • Place of Presentation
      京都
    • Year and Date
      2015-12-06
    • Related Report
      2015 Research-status Report
  • [Presentation] VHL病のデータとゲノム医療の展開2015

    • Author(s)
      高柳 俊作、武笠 晃丈、中冨 浩文、菅野 洋、執印 太郎、齊藤 延人
    • Organizer
      日本脳神経外科学会第74回学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2015-10-15
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 結節性硬化症に合併した膠芽腫に対する分子病理学的解析2015

    • Author(s)
      高柳 俊作、武笠 晃丈、長谷川 洋敬、田中 将太、相原 功輝、柳澤 俊介、野村 昌志、高橋 長久、滝田 順子、小林 敏之、樋野 興夫、水口 雅、齊藤 延人
    • Organizer
      第16回日本分子脳神経外科学会
    • Place of Presentation
      浜松
    • Year and Date
      2015-08-28
    • Related Report
      2015 Research-status Report
  • [Presentation] 中枢神経系血管芽腫に対するゲノム 医療体制の構築2014

    • Author(s)
      高柳俊作、武笠晃丈、中冨浩文、斉藤延人
    • Organizer
      第32回日本脳腫瘍学会学術集会
    • Place of Presentation
      浦安
    • Year and Date
      2014-11-30
    • Related Report
      2014 Research-status Report
  • [Presentation] 家族性腫瘍疾患VH L病に対するゲノム医療の展開2014

    • Author(s)
      高柳俊作、武笠晃丈、中冨浩文、斉藤延人、後藤 順、辻 省次
    • Organizer
      第59回日本人類遺伝学会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-21
    • Related Report
      2014 Research-status Report
  • [Presentation] VHL病におけるゲノム医療の展開2014

    • Author(s)
      高柳俊作、武笠晃丈、中冨浩文、斉藤延人
    • Organizer
      第73回 日 本脳神経外科学会 学術総会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] VHL病に伴う中枢神経系 病変の治療戦略 ー病変局在と術前後mRS変化の相関関係ー2014

    • Author(s)
      高柳俊作、中冨浩文、花北俊哉、井上瑞穂、武笠晃丈、斉藤延人
    • Organizer
      第19回日本脳腫瘍の外科学会
    • Place of Presentation
      東京
    • Year and Date
      2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] PDGFRBのgerm line変異を認めたinfantile myofibromatosisの1例2014

    • Author(s)
      高柳俊作、田中将太、井上瑞穂、武笠晃丈、中冨浩文、斉藤延人
    • Organizer
      第20回日本家族性腫瘍学会学術集会
    • Place of Presentation
      福島
    • Year and Date
      2014-06-13
    • Related Report
      2014 Research-status Report
  • [Book] 脳腫瘍の部位別発症頻度と問題点 脳腫瘍学 日本臨床 2016年9月増刊号2016

    • Author(s)
      武笠晃丈、田中將太、斉藤延人
    • Total Pages
      4
    • Publisher
      日本臨牀社
    • Related Report
      2016 Annual Research Report
  • [Book] 血管芽腫. 第4版 EBMに基づく脳神経疾患の基本治療指針2016

    • Author(s)
      高柳 俊作、武笠 晃丈、中冨 浩文、齊藤 延人
    • Total Pages
      2
    • Publisher
      メジカルビュー社
    • Related Report
      2016 Annual Research Report
  • [Book] von Hippel-Lindau病. 第4版 EBMに基づく脳神経疾患の基本治療指針2016

    • Author(s)
      高柳 俊作、武笠 晃丈、中冨 浩文、齊藤 延人
    • Total Pages
      2
    • Publisher
      メジカルビュー社
    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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